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Silva DL, Peres NTA, Santos DA. Key fungal coinfections: epidemiology, mechanisms of pathogenesis, and beyond. mBio 2025; 16:e0056225. [PMID: 40172196 PMCID: PMC12077096 DOI: 10.1128/mbio.00562-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2025] Open
Abstract
Coinfection is defined as the occurrence of at least two genetically distinct infectious agents within the same host. Historically, fungal infections have been neglected, leading to an underestimation of their impact on public health systems. However, fungal coinfections have become increasingly prevalent, emerging as a significant global health concern. This review explores fungal coinfections commonly associated with HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, Mycobacterium tuberculosis, and Pseudomonas species. These include candidiasis, aspergillosis, paracoccidioidomycosis, cryptococcosis, histoplasmosis, pneumocystosis, sporotrichosis, and mucormycosis. We discuss the key local and systemic mechanisms that contribute to the occurrence of these coinfections. HIV infects CD4+ cells, causing systemic immunosuppression, particularly impairing the adaptive immune response. The inflammatory response to SARS-CoV-2 infection disrupts both pulmonary and systemic homeostasis, rendering individuals more vulnerable to local and disseminated fungal coinfections. Severe influenza promotes fungal coinfections by triggering the production of pro-inflammatory cytokines, which damage the epithelial-endothelial barrier and impair the recognition and phagocytosis of fungal cells. Tuberculosis can replace normal lung parenchyma with collagen tissue, leading to alterations in lung architecture, compromising its function. Interaction between Pseudomonas and Aspergillus during coinfection involves the competition for iron availability and an adaptive response to its deprivation. Therefore, the specific interactions between each underlying disease and fungal coinfections are detailed in this review. In addition, we highlight the risk factors associated with coinfections, pathophysiology, epidemiology, and the challenges of early diagnosis. Recognizing the substantial worldwide public health burden posed by fungal coinfections is crucial to improve survival rates.
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Affiliation(s)
- Danielle L. Silva
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
| | - Nalu T. A. Peres
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
- Brazilian National Institute of Science and Technology in Human Pathogenic Fungi (INCT-FUNVIR), São Paulo, Brazil
| | - Daniel A. Santos
- Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil
- Brazilian National Institute of Science and Technology in Human Pathogenic Fungi (INCT-FUNVIR), São Paulo, Brazil
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Benders PMB, Schouten J, Vena A, Buil JB, Bronkhorst E, Bassetti M. Creating a prediction model for invasive candidiasis in the intensive care unit using a case control design: a European multicentre approach. BMC Infect Dis 2025; 25:655. [PMID: 40320529 PMCID: PMC12051287 DOI: 10.1186/s12879-025-10644-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 02/14/2025] [Indexed: 05/08/2025] Open
Abstract
PURPOSE Invasive candidiasis (IC) has a high attributable morbidity and mortality in patients in the intensive care unit (ICU). Current diagnostic tools lack sensitivity, introduce delay or have not been validated for regular use. As early treatment has proven vital for survival, multiple prediction models have been proposed but have not been validated for multinational implementation. In this study we propose to find factors predisposing the ICU patient to develop IC. We hope to develop an alternative prediction model using a large international dataset. METHODS Using ICU-acquired IC as primary endpoint we retrieved retrospective information about 285 cases and 285 matched controls from the EUCANDICU database. Data about comorbidities, severity of illness and known risk factors for IC were available. We identified 31 independent risk factors using univariate analysis. A random subset of 80% of the observations were used to find the optimal prediction model. The selection of predictors was done using the LASSO technique, using λ = 1SE as regularization parameter. This choice for λ implies that a small amount of precision of the prediction is sacrificed to improve the external validity. The remaining 20% of cases were used to assess the predictive performance of the model. RESULTS Among other factors SAPS II score, SOFA score, past infection, renal impairment and the presence of multiple Candida colonization sites were all independently associated with an increased risk of developing IC. We incorporated 22 of 31 variables in a LASSO regression analysis which showed an AUROC of 0.7433. CONCLUSION Predicting which ICU patient will develop invasive candidiasis remains challenging, despite using an alternative methodology in a large multinational database. The performance of this prediction model is not good enough to be used in clinical practice.
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Affiliation(s)
- P M B Benders
- Department of Anesthesiology, Radboudumc, Nijmegen, The Netherlands
| | - J Schouten
- Department of Intensive Care Medicine, Radboudumc, Nijmegen, The Netherlands.
| | - A Vena
- Department of Infectious Diseases, San Martino University Hospital, Genua, Italy
| | - J B Buil
- Department of Microbiology, Radboudumc, Nijmegen, The Netherlands
| | - E Bronkhorst
- Department of Biostatistics, Radboudumc, Nijmegen, The Netherlands
| | - M Bassetti
- Department of Infectious Diseases, San Martino University Hospital, Genua, Italy
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Vaivoothpinyo S, Jantarathaneewat K, Weber DJ, Camins BC, Apisarnthanarak P, Rutjanawech S, Apisarnthanarak A. The patterns of antifungal use and risk factors associated with mortality in patients with invasive candidiasis and aspergillosis infections among patients who were received infectious disease specialist consultation prior to and during the COVID-19 pandemic in a resource-limited setting: A retrospective cohort study. Am J Infect Control 2025; 53:314-319. [PMID: 39427929 DOI: 10.1016/j.ajic.2024.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/14/2024] [Accepted: 10/14/2024] [Indexed: 10/22/2024]
Abstract
BACKGROUND Limited data is available concerning the patterns of antifungal use and Invasive fungal infection (IFI)-associated mortality risk factors in patients with IFI prior to and during the Coronavirus disease 2019 (COVID-19) pandemic in resource-limited settings. METHODS A single-center retrospective cohort study was conducted. All patients age >18 years diagnosed with IFIs were prospectively followed during a 3-year pre-COVID-19 pandemic period and a 3-year during COVID-19 pandemic period. Patient characteristics, the patterns of antifungal use, IFI-associated mortality risk factors, and adverse drug events were collected. RESULTS There was a total of 133 patients in this study: 60 (45.1%) were in period 1 and 73 (54.9%) were in period 2. Pre-emptive antifungal therapy was commonly practiced in period 2 (21.7% vs 37%, P = .05). The presence of a central venous catheter (aOR 3.19, P = .007), hematologic adverse drug events (aOR 17.9, P = .008) were preventable risks for the overall IFI mortality in both periods. Appropriate antifungal use was protective against the overall IFI mortality in period 2 (aOR 0.09, P = .009). CONCLUSIONS Several preventable risk factors associated with mortality were identified and served as a key for improvement of infection prevention, national policy to access antifungal agents, and antifungal stewardship in resource-limited settings.
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Affiliation(s)
- Supavit Vaivoothpinyo
- Division of Infectious Diseases, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Kittiya Jantarathaneewat
- Department of Pharmaceutical Care, Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand; Research Group in Infectious Diseases Epidemiology and Prevention, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - David J Weber
- Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Bernard C Camins
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Piyaporn Apisarnthanarak
- Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sasinuch Rutjanawech
- Division of Infectious Diseases, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Research Group in Infectious Diseases Epidemiology and Prevention, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand
| | - Anucha Apisarnthanarak
- Division of Infectious Diseases, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Research Group in Infectious Diseases Epidemiology and Prevention, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
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Jin W, Yang D, Xu Z, Song J, Jin H, Zhou X, Liu C, Wu H, Cheng Q, Yang J, Lin J, Wang L, Chen C, Wang Z, Weng J. Predicting the risk of invasive fungal infections in ICU sepsis population: the AMI risk assessment tool. Infection 2025:10.1007/s15010-024-02465-w. [PMID: 39899210 DOI: 10.1007/s15010-024-02465-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 12/21/2024] [Indexed: 02/04/2025]
Abstract
BACKGROUND Invasive fungal infections (IFI) represent a significant contributor to mortality among sepsis patients in the Intensive Care Unit (ICU). Early diagnosis of IFI is challenging, and currently, there are no predictive tools for identifying sepsis patients who may develop IFI. Our study aims to develop a predictive scoring system to assess the risk of IFI in patients with sepsis admitted to the ICU. METHODS A retrospective collection of data from a total of 549 patients was conducted. Data-driven, clinically knowledge-driven, and decision tree models were used to identify predictive variables for risk of IFI in ICU patients with sepsis. Demographic data, vital signs, laboratory values, comorbidities, medication use, and clinical outcomes were all collected. The optimal model was selected based on model performance and clinical utility to establish a risk score. RESULTS Among adult patients with sepsis admitted to the ICU, 127 patients (23.1%) developed IFI. The final data-driven model included four predictive factors, the clinically knowledge-driven model included three predictive factors, and the decision tree model included two. Based on the good performance and clinical utility of the clinically knowledge-driven model, it was chosen as the optimal risk scoring model (C-statistics: 0.79 (95% confidence interval (CI): 0.75-0.83); Hosmer-Lemeshow (H-L) test P = 0.884). The ICU sepsis patient invasive fungal infection risk (AMI) score, created based on the clinically knowledge-driven model, includes mechanical ventilation, application of immunosuppressants, and the types of antibiotics used. The C-statistics for this risk score was 0.79 (95% CI:0.75-0.84) with good calibration (H-L test P = 0.992 and see calibration curve: Fig. 2). Moreover, in terms of clinical utility, the decision curve analysis for AMI showed a favorable net benefit. CONCLUSIONS The application of the AMI score can effectively distinguish whether ICU sepsis patients will develop IFI, which is beneficial for clinicians to formulate targeted and timely preventive and treatment measures based on the risk of IFI.
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Affiliation(s)
- Wenyi Jin
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, 325000, China
| | - Donglin Yang
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Zhe Xu
- Department of Intensive Care Unit, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
| | - Jiaze Song
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
| | - Haijuan Jin
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, Zhejiang, 325000, China
| | - Xiaoming Zhou
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, 325000, China
| | - Chen Liu
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, 325000, China
| | - Hao Wu
- Taishun County People's Hospital Medical Community Sixi Branch, Taishun, Zhejiang, 325500, China
| | - Qianhui Cheng
- Department of Geriatric Medicine, The First Affiliated Hospital, Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, Zhejiang Province, 325000, China
| | - Jingwen Yang
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Department of General Practice, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, 318001, China
| | - Jiaying Lin
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China
- Department of General Practice, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, 318001, China
| | - Liang Wang
- Department of Public Health, Marshall University, West, VA, USA
| | - Chan Chen
- Department of Geriatric Medicine, The First Affiliated Hospital, Wenzhou Medical University, No. 2, Fuxue Lane, Wenzhou, Zhejiang Province, 325000, China.
- South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, 325014, China.
| | - Zhiyi Wang
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
- Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, 325000, China.
- Department of General Practice, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou, 318001, China.
- South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, 325014, China.
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road, Wenzhou, Zhejiang Province, 325000, China.
| | - Jie Weng
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.
- Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou, 325000, China.
- South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, 325014, China.
- Department of General Practice, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road, Wenzhou, Zhejiang Province, 325000, China.
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Khemani P, Srinivasan S, Salunke G, Prasad M, Dhamne C, Parambil BC, Chichra A, Gollamudi VRM, Sunder IR, Moulik NR, Narula G, Chinnaswamy G, Banavali S. Prevalence and outcome of candidemia among paediatric cancer patients: A single centre experience from India. J Mycol Med 2024; 34:101510. [PMID: 39510020 DOI: 10.1016/j.mycmed.2024.101510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 08/15/2024] [Accepted: 10/22/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND Candida species are one of the leading causes of invasive fungal infections in pediatric patients with cancer, resulting in increased treatment related morbidity and mortality. There is limited data with respect to demography and outcomes of candidemia among children with cancer, especially from lower-middle income countries. METHODS In this retrospective observational study conducted over a 4-year Period (January-2017 to December-2021), children less than 15 years with cancer, treated at a tertiary oncology centre in India and diagnosed with candidemia were included. Data with respect to risk factors, species types, treatment, complications and mortality was gathered. RESULTS One-hundred and ten children with candidemia were included. The most common underlying malignancy was acute leukemia seen in 72 (66%) patients. Seventy-five (68%) patients had neutropenia (<0.5 × 10^9/L) at the time of diagnosis of candidemia. In addition, 35 (32%) and 34 (30%) patients had prolonged exposure to steroids and antibiotics respectively. Non-albicans Candida species was isolated in majority (90%) of the cases. Fifty-seven patients required some form of modification of therapy for underlying malignancy. The 30-day mortality of the entire cohort was 36% and was 73% for patients admitted to the intensive care unit. On multivariate analysis, only prolonged use of antibiotics [odds ratio: 2.7(1.1-6.7); p = 0.027] was found to be significantly associated with worse 30-day mortality. CONCLUSION The present study highlights the burden of candidemia among children with cancer. Despite prompt therapy, our cohort experienced increased mortality, primarily associated with prolonged antibiotic usage. These findings reinforce the critical importance of strict adherence to infection control guidelines and prudent antibiotic stewardship practices to improve patient outcomes.
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Affiliation(s)
- Poonam Khemani
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shyam Srinivasan
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
| | - Gaurav Salunke
- Department of Microbiology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Maya Prasad
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Chetan Dhamne
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Badira C Parambil
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akanksha Chichra
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Venkata Rama Mohan Gollamudi
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Irene Ruben Sunder
- Nursing officer In-charge, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Nirmalya Roy Moulik
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Gaurav Narula
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Girish Chinnaswamy
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shripad Banavali
- Division of Pediatric oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Suárez-Urquiza P, Pemán J, Gordon M, Favier P, Muñoz-Brell P, López-Hontangas JL, Ruiz-Gaitán A. Predicting Fungemia in the ICU: Unveiling the Value of Weekly Fungal Surveillance and Yeast Colonisation Monitoring. J Fungi (Basel) 2024; 10:674. [PMID: 39452626 PMCID: PMC11508630 DOI: 10.3390/jof10100674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/18/2024] [Accepted: 09/25/2024] [Indexed: 10/26/2024] Open
Abstract
Fungemia remains a major threat in intensive care units (ICUs), with high mortality rates despite advances in diagnostics and treatment. Colonisation by yeasts is an independent risk factor for fungemia; however, its predictive utility requires further research. In this 8-year study, we analysed 38,017 samples from 3206 patients and 171 fungemia episodes as part of a weekly fungal surveillance programme. We evaluated species-specific colonisation patterns, the predictive value of the Colonisation Index (CI) and Corrected Colonisation Index (CCI), and candidemia risks associated with different yeast species and anatomical site colonisation. Our results showed that C. auris, N. glabratus, and C. parapsilosis colonisation increased with longer hospital stays (0.8% to 11.55%, 8.13% to 16.8%, and 1.93% to 5.14%, respectively). The CI and CCI had low discriminatory power (AUROC 67% and 66%). Colonisation by any yeast genera demonstrated high sensitivity (98.32%) and negative predictive value (NPV) (95.90%) but low specificity and positive predictive value (PPV) (23.90% and 6.64%). Tracheal and urine cultures had the highest PPV (15.64% and 12.91%), while inguinal cultures had the highest NPV (98.60%). C. auris (12.32%) and C. parapsilosis (5.5%) were associated with a higher fungemia risk (log-rank < 0.001). These findings support the use of weekly surveillance to better stratify the fungemia risk and optimise antifungal use in ICUs.
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Affiliation(s)
- Pedro Suárez-Urquiza
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
| | - Javier Pemán
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
| | - Monica Gordon
- Department of Intensive Care Unit, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain;
| | - Patricio Favier
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
| | - Paula Muñoz-Brell
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
| | - Jose Luis López-Hontangas
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
| | - Alba Ruiz-Gaitán
- Department of Medical Microbiology, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain; (J.P.); (P.F.); (P.M.-B.); (J.L.L.-H.)
- Severe Infection Research Group, Health Research Institute La Fe, 46026 Valencia, Spain
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7
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Salmanton-García J, Cornely OA, Stemler J, Barać A, Steinmann J, Siváková A, Akalin EH, Arikan-Akdagli S, Loughlin L, Toscano C, Narayanan M, Rogers B, Willinger B, Akyol D, Roilides E, Lagrou K, Mikulska M, Denis B, Ponscarme D, Scharmann U, Azap A, Lockhart D, Bicanic T, Kron F, Erben N, Rautemaa-Richardson R, Goodman AL, Garcia-Vidal C, Lass-Flörl C, Gangneux JP, Taramasso L, Ruiz M, Schick Y, Van Wijngaerden E, Milacek C, Giacobbe DR, Logan C, Rooney E, Gori A, Akova M, Bassetti M, Hoenigl M, Koehler P. Attributable mortality of candidemia - Results from the ECMM Candida III multinational European Observational Cohort Study. J Infect 2024; 89:106229. [PMID: 39025408 DOI: 10.1016/j.jinf.2024.106229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/05/2024] [Accepted: 07/06/2024] [Indexed: 07/20/2024]
Abstract
INTRODUCTION Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections. METHODS In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed. RESULTS One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004). CONCLUSIONS Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.
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Affiliation(s)
- Jon Salmanton-García
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Oliver A Cornely
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
| | - Jannik Stemler
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany
| | - Aleksandra Barać
- Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jörg Steinmann
- Institute for Clinical Hygiene and Medical Microbiology, Paracelsus Medical University, Nuremberg, Germany
| | - Alena Siváková
- Department of Microbiology, St Anne's Faculty Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Emin Halis Akalin
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Bursa Uludağ University, Bursa, Turkey
| | - Sevtap Arikan-Akdagli
- Department of Medical Microbiology, Hacettepe University Medical School, Ankara, Turkey
| | - Laura Loughlin
- Belfast Health and Social Care Trust, Belfast, United Kingdom
| | - Cristina Toscano
- Laboratory of Clinical Microbiology and Molecular Biology, Centro Hospitalar de Lisboa Ocidental, Lisboa, Portugal
| | - Manjusha Narayanan
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
| | - Benedict Rogers
- Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
| | - Birgit Willinger
- Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Deniz Akyol
- Ege Univerisity Infectious Diseases and Clinical Microbiology, Izmir, Turkey
| | - Emmanuel Roilides
- Infectious Diseases Department, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Katrien Lagrou
- Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | | | - Blandine Denis
- Department of Infectious Diseases, Hôpital Saint-Louis, Fernand Widal, Lariboisière, AP-HP, 1 Avenue Claude Vellefaux, 75010 Paris, France
| | | | - Urlike Scharmann
- Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | | | - Deborah Lockhart
- Institute of Medical Sciences, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom; Department of Medical Microbiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK, School of Medicine Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Tihana Bicanic
- Clinical Academic Group in Infection and Immunity, St. George's University Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Florian Kron
- VITIS Healthcare Group, Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO ABCD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; FOM University of Applied Sciences, Essen, Germany
| | - Nurettin Erben
- Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
| | - Riina Rautemaa-Richardson
- Mycology Reference Centre Manchester, ECMM Centre of Excellence, and Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Anna L Goodman
- Department of Infectious Diseases, Centre for Clinical Infection and Diagnostics Research (CIDR), Guy's and St Thomas' National Health Service Foundation Trust and King's College London, and Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom
| | | | - Cornelia Lass-Flörl
- Institute of Hygiene and Medical Microbiology, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Innsbruck Medical University, Innsbruck, Austria
| | - Jean-Pierre Gangneux
- University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, Rennes, France
| | - Lucia Taramasso
- Departement of Internal Medicine Fondazione IRCCS Cà Granda Osepdale Maggiore Policlinico, Milan, Italy
| | - Maite Ruiz
- UGC Enfermedades Infecciosas, Microbiología y Parasitología, University Hospital Virgen del Rocío, Seville, Spain; Grupo Microbiología Clínica y Molecular, Instituto de Biomedicina de Sevilla, HUVR/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Madrid, Spain
| | - Yael Schick
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany
| | - Eric Van Wijngaerden
- Laboratory of Clinical Microbiology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Christopher Milacek
- Division of Clinical Microbiology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Clare Logan
- Clinical Academic Group in Infection and Immunity, St. George's University Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
| | - Emily Rooney
- Department of Infectious Diseases, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Andrea Gori
- Departement of Internal Medicine Fondazione IRCCS Cà Granda Osepdale Maggiore Policlinico, Milan, Italy
| | - Murat Akova
- Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Medical School, Ankara, Turkey
| | - Matteo Bassetti
- IRCCS Ospedale Policlinico San Martino di Genova, Genoa, Italy
| | - Martin Hoenigl
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Translational Medical Mycology Research Unit, European Confederation of Medical Mycology Excellence Center for Medical Mycology, Medical University of Graz, Graz, Austria; BioTechMed, Graz, Austria.
| | - Philipp Koehler
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
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8
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Belgacem S, Chebil W, Ben Salem S, Babba O, Mastouri M, Babba H. Identification and antifungal susceptibility profile of uncommon yeast species at Fattouma Bourguiba University Hospital in Tunisia. Med Mycol 2024; 62:myae070. [PMID: 38986508 DOI: 10.1093/mmy/myae070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 06/18/2024] [Accepted: 07/08/2024] [Indexed: 07/12/2024] Open
Abstract
Despite the severe impact of uncommon yeast fungal infections and the pressing need for more research on the topic, there are still few studies available on the identification, epidemiology, and susceptibility profile of those pathogens. The aims of the current study were to define the profile of uncommon yeast species at Fattouma Bourguiba University Hospital using phenotypic, molecular, and proteomic methods and to study their antifungal susceptibility profile. Pre-identified uncommon yeast species were collected from 2018 to 2021. These isolates were further identified using phenotypic methods (ID32C® system and Vitek2® YST), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and sequencing. The antifungal susceptibility profile was studied using the reference CLSI broth microdilution method. In total, 30 strains were collected during the study period. Referring to the sequencing, the most isolated uncommon species were Saprochaete capitata, Candida lusitaniae, Candida kefyr, Candida inconspicua, and Candida guilliermondii. A total of 90% of isolates were correctly identified by MALDI-TOF MS compared to 76.7% and 63.3% by ID32® C and VITEK® 2 YST, respectively. The isolated species showed variable responses to antifungals. Candida guilliermondii showed increased azole minimum inhibitory concentrations. Misidentification of uncommon yeast species was common using commercial phenotypic methods. The high percentage of concordance of MALDI-TOF results with sequencing highlights its high performance and usefulness as a routine diagnosis tool.
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Affiliation(s)
- Sameh Belgacem
- Unit of Parasitology-Mycology, Laboratory of Microbiology, Fattouma Bourguiba University Hospital, Monastir, Tunisia
- Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), Department of Clinical Biology B, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
| | - Wissal Chebil
- Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), Department of Clinical Biology B, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
| | - Safa Ben Salem
- Unit of Parasitology-Mycology, Laboratory of Microbiology, Fattouma Bourguiba University Hospital, Monastir, Tunisia
| | - Oussama Babba
- Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), Department of Clinical Biology B, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
| | - Maha Mastouri
- Unit of Parasitology-Mycology, Laboratory of Microbiology, Fattouma Bourguiba University Hospital, Monastir, Tunisia
| | - Hamouda Babba
- Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), Department of Clinical Biology B, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia
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9
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Theodore DA, Henneman AD, Loo A, Shields RK, Eschenauer G, Sobieszczyk ME, Kubin CJ. Initial micafungin treatment does not improve outcomes compared to fluconazole treatment in immunocompromised and critically ill patients with candidaemia. J Antimicrob Chemother 2024; 79:1877-1884. [PMID: 38831614 PMCID: PMC11290885 DOI: 10.1093/jac/dkae175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 05/13/2024] [Indexed: 06/05/2024] Open
Abstract
BACKGROUND Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES To understand optimal initial treatment of candidaemia. METHODS We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.
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Affiliation(s)
- Deborah A Theodore
- Department of Medicine, Division of Infectious Diseases, New York-Presbyterian Hospital, Columbia University Medical Center, 622 West 168th Street, PH 8W-876, New York, NY 10032, USA
| | - Amrita D Henneman
- Hofstra Northwell School of Nursing and Physician Assistant Studies, 160 Hofstra University, Hempstead, New York, 11549, USA
| | - Angela Loo
- Department of Pharmacy, New York-Presbyterian Hospital, 630 W 168th Street, 3rd Floor, New York, NY 10032, USA
| | - Ryan K Shields
- Department of Medicine, University of Pittsburgh, Falk Medical Building, Suite 3A, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA
| | - Gregory Eschenauer
- Department of Pharmacy, Michigan Medicine, College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109-1065, USA
| | - Magdalena E Sobieszczyk
- Department of Medicine, Division of Infectious Diseases, New York-Presbyterian Hospital, Columbia University Medical Center, 622 West 168th Street, PH 8W-876, New York, NY 10032, USA
| | - Christine J Kubin
- Department of Medicine, Division of Infectious Diseases, New York-Presbyterian Hospital, Columbia University Medical Center, 622 West 168th Street, PH 8W-876, New York, NY 10032, USA
- Department of Pharmacy, New York-Presbyterian Hospital, 630 W 168th Street, 3rd Floor, New York, NY 10032, USA
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10
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Huang L, Li S, Jiang R, Lei S, Wu J, Huang L, Zhu M. Glucocorticoid use and parenteral nutrition are risk factors for catheter-related Candida bloodstream infection: a retrospective study. ASIAN BIOMED 2024; 18:109-115. [PMID: 39175949 PMCID: PMC11337845 DOI: 10.2478/abm-2024-0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/24/2024]
Abstract
Background Catheter-related candidemia (CRC) is a serious catheter-related bloodstream infection (CRBSI) caused by Candida spp., with higher mortality than CRBSIs caused by other organisms. Objective To identify the risk factors for Candida CRBSI. The clinical characteristics of 297 patients with CRBSI in a local hospital from January 2007 to June 2015 were collected, including 33 Candida CRBSI and 264 non-Candida CRBSI. Method The associations of Candida CRBSI with the clinical variables were examined using univariate and multivariate analyses. Results Multivariate analysis showed that glucocorticoid use (odds ratio [OR] = 10.313, 95% confidence interval [CI] = 2.032-52.330, P = 0.005) and parenteral nutrition (OR = 5.400, 95% CI = 0.472-61.752, P = 0.0175) were independent risk factors for Candida CRBSI. The most prevalent species were Candida tropicalis (42.4%) and Candida albicans (36.36%). Of the 33 Candida CRBSI cases, 31 (93.93%) had indwelling central venous catheters (CVC) for ≥14 d. The mortality of Candida CRBSI was remarkably higher than that of bacteria CRBSI. Patients with timely catheter removal and appropriate antifungal treatment had dramatically increased 28-d survival compared with those with untimely catheter removal + inappropriate antifungal treatment (88.89% vs. 0, P = 0.006). Conclusion The study identified glucocorticoid use and parenteral nutrition as independent risk factors for Candida CRBSI. The outcome of candidemia was associated with the duration of CVC indwelling and antifungal treatment.
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Affiliation(s)
- Lipeng Huang
- The Intensive Care Unit, Taizhou Cancer Hospital of Zhejiang Province, Taizhou, Zhejiang317500, China
| | - Shanshan Li
- Xiaoying District Community Health Service Center, Hangzhou, Zhejiang310006, China
| | - Ronglin Jiang
- The Intensive Care Unit, The First Affiliated Hospital of Zhejiang University of the Traditional Chinese Medicine, Hangzhou, Zhejiang310006, China
| | - Shu Lei
- The Intensive Care Unit, The First Affiliated Hospital of Zhejiang University of the Traditional Chinese Medicine, Hangzhou, Zhejiang310006, China
| | - Jiannong Wu
- The Intensive Care Unit, The First Affiliated Hospital of Zhejiang University of the Traditional Chinese Medicine, Hangzhou, Zhejiang310006, China
| | - Liquan Huang
- The Intensive Care Unit, The First Affiliated Hospital of Zhejiang University of the Traditional Chinese Medicine, Hangzhou, Zhejiang310006, China
| | - Meifei Zhu
- Xiaoying District Community Health Service Center, Hangzhou, Zhejiang310006, China
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11
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Bassetti M, Giacobbe DR, Agvald-Ohman C, Akova M, Alastruey-Izquierdo A, Arikan-Akdagli S, Azoulay E, Blot S, Cornely OA, Cuenca-Estrella M, de Lange DW, De Rosa FG, De Waele JJ, Dimopoulos G, Garnacho-Montero J, Hoenigl M, Kanj SS, Koehler P, Kullberg BJ, Lamoth F, Lass-Flörl C, Maertens J, Martin-Loeches I, Muñoz P, Poulakou G, Rello J, Sanguinetti M, Taccone FS, Timsit JF, Torres A, Vazquez JA, Wauters J, Asperges E, Cortegiani A, Grecchi C, Karaiskos I, Le Bihan C, Mercier T, Mortensen KL, Peghin M, Rebuffi C, Tejada S, Vena A, Zuccaro V, Scudeller L, Calandra T. Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM. Intensive Care Med 2024; 50:502-515. [PMID: 38512399 PMCID: PMC11018656 DOI: 10.1007/s00134-024-07341-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/31/2024] [Indexed: 03/23/2024]
Abstract
PURPOSE The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.
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Affiliation(s)
- Matteo Bassetti
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
- Infectious Diseases Unit, IRCCS Ospedale Policlinico San Martino, L.go R. Benzi 10, 16132, Genoa, Italy.
| | - Daniele R Giacobbe
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
- Infectious Diseases Unit, IRCCS Ospedale Policlinico San Martino, L.go R. Benzi 10, 16132, Genoa, Italy
| | - Christina Agvald-Ohman
- Anaesthesiology and Intensive Care, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Murat Akova
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ana Alastruey-Izquierdo
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas-CIBERINFEC, Madrid, Spain
| | - Sevtap Arikan-Akdagli
- Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Elie Azoulay
- Université de Paris, Paris, France
- Service de Médecine Intensive Et Réanimation, Hôpital Saint-Louis, AP-HP, Paris, France
| | - Stijn Blot
- Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | - Oliver A Cornely
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Faculty of Medicine and University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster On Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
- Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Manuel Cuenca-Estrella
- Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Dylan W de Lange
- Department of Intensive Care Medicine, University Medical Center, University Utrecht, Utrecht, The Netherlands
| | - Francesco G De Rosa
- Department of Medical Sciences, Infectious Diseases, University of Turin, Turin, Italy
| | - Jan J De Waele
- Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium
| | - George Dimopoulos
- Department of Critical Care, University Hospital Attikon, Attikon Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Martin Hoenigl
- Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria
- BioTechMed, Graz, Austria
- Translational Mycology Working Group, ECMM Excellence Center for Clinical Mycology, Medical University of Graz, Graz, Austria
| | - Souha S Kanj
- Division of Infectious Diseases, and Center for Infectious Diseases Research, American University of Beirut Medical Center, Beirut, Lebanon
| | - Philipp Koehler
- Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Medical Faculty and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
| | - Bart J Kullberg
- Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Frédéric Lamoth
- Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Service of Immunology and Allergy and Center of Human Immunology Lausanne, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Cornelia Lass-Flörl
- Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James' Hospital, Dublin, Ireland
| | - Patricia Muñoz
- Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
- Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
- Medicine Department, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Garyphallia Poulakou
- Third Department of Internal Medicine, School of Medicine, Sotiria General Hospital, National and Kapodistrian University, Athens, Greece
| | - Jordi Rello
- Clinical Research/Epidemiology in Pneumonia and Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
- Clinical Research in the ICU, CHU Nimes, Universite de Nimes-Montpellier, Nimes, France
- Medicine Department, Universitat Internacional de Catalunya (UIC), Sant Cugat, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
| | - Maurizio Sanguinetti
- Dipartimento di Scienze di Laboratorio E Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Fabio S Taccone
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Jean-François Timsit
- Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat Claude Bernard University Hospital, Paris, France
- IAME UMR 1137, Université Paris-Cité, Paris, France
| | - Antoni Torres
- Department of Pneumology, Hospital Clinic of Barcelona, Barcelona, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain
- Biomedical Research Networking Centres in Respiratory Diseases (CIBERES), Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
| | - Jose A Vazquez
- Department of Medicine/Division of Infectious Disease, Medical College of Georgia/Augusta University, Augusta, GA, USA
| | - Joost Wauters
- Medical Intensive Care Unit, University Hospitals Leuven, Louvain, Belgium
| | - Erika Asperges
- Infectious Diseases Unit, IRCCS San Matteo, Pavia, Italy
| | - Andrea Cortegiani
- Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), University of Palermo, Palermo, Italy
- Department of Anesthesia Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, Palermo, Italy
| | - Cecilia Grecchi
- Malattie Infettive, Azienda Socio Sanitaria Territoriale (ASST) di Lodi, Lodi, Italy
| | - Ilias Karaiskos
- 1st Department of Internal Medicine-Infectious Diseases, Hygeia General Hospital, Athens, Greece
| | - Clément Le Bihan
- Saint Eloi Department of Anesthesiology and Critical Care Medicine, Montpellier University Health Care Center, Montpellier, France
| | - Toine Mercier
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Louvain, Belgium
- Department of Hematology, University Hospitals Leuven, Louvain, Belgium
| | - Klaus L Mortensen
- Department of Medicine, Regional Hospital West Jutland, Herning, Denmark
| | - Maddalena Peghin
- Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria-ASST-Sette Laghi, Varese, Italy
| | - Chiara Rebuffi
- Scientific Direction, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Sofia Tejada
- Clinical Research/Epidemiology in Pneumonia and Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
| | - Antonio Vena
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
- Infectious Diseases Unit, IRCCS Ospedale Policlinico San Martino, L.go R. Benzi 10, 16132, Genoa, Italy
| | | | - Luigia Scudeller
- Research and Innovation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Thierry Calandra
- Service of Immunology and Allergy and Center of Human Immunology Lausanne, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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12
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Ijiri A, Terayama T, Sugiura H, Kaneko M, Seno S, Kiriu N, Kato H, Sekine Y, Shinmoto H, Kiyozumi T. Invasive candidiasis presenting bronchiectatic cavity as chest radiological findings: A case report. Radiol Case Rep 2023; 18:3467-3470. [PMID: 37539445 PMCID: PMC10393609 DOI: 10.1016/j.radcr.2023.07.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/07/2023] [Accepted: 07/08/2023] [Indexed: 08/05/2023] Open
Abstract
Invasive candidiasis is rare but is associated with high mortality in immunocompromised or critically ill patients. Here, we present a case of a 55-year-old man with untreated diabetes who was diagnosed with coronavirus disease 2019 and subsequently developed invasive candidiasis. The patient presented with fever, tachycardia, and tachypnea. Chest computed tomography revealed multiple consolidations mainly distributed around the bronchovascular bundles with bronchiectatic cavity formation, which initially raised suspicion for invasive pulmonary aspergillosis. However, subsequent testing confirmed Candida albicans infection; hence, we changed the antifungal agents effective for invasive candidiasis. This improved the patient's respiratory status, and he was then successfully weaned from mechanical ventilation. This case report highlights the importance of considering invasive candidiasis in the differential diagnosis of patients with bronchiectatic cavities on chest computed tomography, particularly in immunocompromised or critically ill patients with risk factors for invasive candidiasis.
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Affiliation(s)
- Atsuhiro Ijiri
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Takero Terayama
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
- Department of Emergency, Self-Defense Forces Central Hospital, Ikeziri 1-2-24, Setagaya, Tokyo, 154-0001, Japan
| | - Hiroaki Sugiura
- Department of Radiology, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Mayuko Kaneko
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Soichiro Seno
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Nobuaki Kiriu
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Hiroshi Kato
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Yasumasa Sekine
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Hiroshi Shinmoto
- Department of Radiology, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
| | - Tetsuro Kiyozumi
- Department of Traumatology and Critical Care Medicine, National Defense Medical College, 3-2 Namiki, Saitama, 359-8513, Japan
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Baker J, Denning DW. The SSS revolution in fungal diagnostics: speed, simplicity and sensitivity. Br Med Bull 2023; 147:62-78. [PMID: 37328942 PMCID: PMC10502448 DOI: 10.1093/bmb/ldad011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 04/24/2023] [Accepted: 05/29/2023] [Indexed: 06/18/2023]
Abstract
INTRODUCTION Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive and time-intensive fungal culture. SOURCES OF DATA We present the recent developments in fungal diagnostics in the fields of serological and molecular diagnosis for the most clinically relevant pathogens; developments that have the potential to revolutionize fungal diagnosis through improvements in speed, simplicity and sensitivity. We have drawn on a body of evidence including recent studies and reviews demonstrating the effectiveness of antigen and antibody detection and polymerase chain reaction (PCR) in patients with and without concurrent human immunodeficiency virus infection. AREAS OF AGREEMENT This includes recently developed fungal lateral flow assays, which have a low cost and operator skill requirement that give them great applicability to low-resource settings. Antigen detection for Cryptococcus, Histoplasma and Aspergillus spp. are much more sensitive than culture. PCR for Candida spp., Aspergillus spp., Mucorales and Pneumocystis jirovecii is more sensitive than culture and usually faster. AREAS OF CONTROVERSY Effort must be made to utilize recent developments in fungal diagnostics in clinical settings outside of specialist centres and integrate their use into standard medical practice. Given the clinical similarities of the conditions and frequent co-infection, further study is required into the use of serological and molecular fungal tests, particularly in patients being treated for tuberculosis. GROWING POINTS Further study is needed to clarify the utility of these tests in low-resource settings confounded by a high prevalence of tuberculosis. AREAS TIMELY FOR DEVELOPING RESEARCH The diagnostic utility of these tests may require revision of laboratory work flows, care pathways and clinical and lab coordination, especially for any facility caring for the immunosuppressed, critically ill or those with chronic chest conditions, in whom fungal disease is common and underappreciated.
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Affiliation(s)
- Jacob Baker
- Department of Medicine, Shrewsbury and Telford Hospitals Trust, Mytton Oak Rd, Shrewsbury SY3 8XQ, UK
| | - David W Denning
- Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
- Global Action For Fungal Infections (GAFFI), Rue Le Corbusier 1208 Geneva, Switzerland
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14
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Asadzadeh M, Ahmad S, Al-Sweih N, Khan Z. Molecular fingerprinting by multi-locus sequence typing identifies microevolution and nosocomial transmission of Candida glabrata in Kuwait. Front Public Health 2023; 11:1242622. [PMID: 37744513 PMCID: PMC10515652 DOI: 10.3389/fpubh.2023.1242622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 08/22/2023] [Indexed: 09/26/2023] Open
Abstract
Backgrounds Candida glabrata is a frequently isolated non-albicans Candida species and invasive C. glabrata infections in older patients are associated with high mortality rates. Opportunistic Candida infections in critically ill patients may be either endogenous or nosocomial in origin and this distinction is critical for effective intervention strategies. This study performed multi-locus sequence typing (MLST) to study genotypic relatedness among clinical C. glabrata isolates in Kuwait. Methods Candida glabrata isolates (n = 91) cultured from 91 patients were analyzed by MLST. Repeat isolates (n = 16) from 9 patients were also used. Antifungal susceptibility testing for fluconazole, voriconazole, caspofungin and amphotericin B (AMB) was determined by Etest. Genetic relatedness was determined by constructing phylogenetic tree and minimum spanning tree by using BioNumerics software. Results Resistance to fluconazole, voriconazole and AMB was detected in 7, 2 and 10 C. glabrata isolates, respectively. MLST identified 28 sequence types (STs), including 12 new STs. ST46 (n = 33), ST3 (n = 8), ST7 (n = 6) and ST55 (n = 6) were prevalent in ≥4 hospitals. Repeat isolates obtained from same or different site yielded identical ST. No association of ST46 with source of isolation or resistance to antifungals was apparent. Microevolution and cross-transmission of infection was indicated in two hospitals that yielded majority (57 of 91, 67%) of C. glabrata. Conclusion Our data suggest that C. glabrata undergoes microevolution in hospital environment and can be nosocomially transmitted to other susceptible patients. Thus, proper infection control practices during routine procedures on C. glabrata-infected patients may prevent transmission of this pathogen to other hospitalized patients.
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Affiliation(s)
| | - Suhail Ahmad
- Department of Microbiology, College of Medicine, Kuwait University, Jabriya, Kuwait
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15
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Ayres AM, Wozniak J, O’Neil J, Stewart K, Leger JS, Pasculle AW, Lewis C, McGrath K, Slivka A, Snyder GM. Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscope reprocessing: Variables impacting contamination risk. Infect Control Hosp Epidemiol 2023; 44:1485-1489. [PMID: 36645014 PMCID: PMC10507511 DOI: 10.1017/ice.2022.319] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/13/2022] [Accepted: 12/15/2022] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To evaluate variables that affect risk of contamination for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound endoscopes. DESIGN Observational, quality improvement study. SETTING University medical center with a gastrointestinal endoscopy service performing ∼1,000 endoscopic retrograde cholangiopancreatography and ∼1,000 endoscopic ultrasound endoscope procedures annually. METHODS Duodenoscope and linear echoendoscope sampling (from the elevator mechanism and instrument channel) was performed from June 2020 through September 2021. Operational changes during this period included standard reprocessing with high-level disinfection with ethylene oxide gas sterilization (HLD-ETO) was switched to double high-level disinfection (dHLD) (June 16, 2020-July 15, 2020), and duodenoscopes changed to disposable tip model (March 2021). The frequency of contamination for the co-primary outcomes were characterized by calculated risk ratios. RESULTS The overall pathogenic contamination rate was 4.72% (6 of 127). Compared to duodenoscopes, linear echoendoscopes had a contamination risk ratio of 3.64 (95% confidence interval [CI], 0.69-19.1). Reprocessing using HLD-ETO was associated with a contamination risk ratio of 0.29 (95% CI, 0.06-1.54). Linear echoendoscopes undergoing dHLD had the highest risk of contamination (2 of 18, 11.1%), and duodenoscopes undergoing HLD-ETO and the lowest risk of contamination (0 of 53, 0%). Duodenoscopes with a disposable tip had a 0% contamination rate (0 of 27). CONCLUSIONS We did not detect a significant reduction in endoscope contamination using HLD-ETO versus dHLD reprocessing. Linear echoendoscopes have a risk of contamination similar to that of duodenoscopes. Disposable tips may reduce the risk of duodenoscope contamination.
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Affiliation(s)
- Ashley M. Ayres
- Department of Infection Prevention and Control, UPMC Presbyterian–Shadyside, Pittsburgh, Pennsylvania
| | - Julia Wozniak
- Department of Infection Prevention and Control, UPMC Presbyterian–Shadyside, Pittsburgh, Pennsylvania
| | - Jose O’Neil
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Kimberly Stewart
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - John St. Leger
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - A. William Pasculle
- Division of Microbiology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Casey Lewis
- Department of Infection Prevention and Control, UPMC Presbyterian–Shadyside, Pittsburgh, Pennsylvania
| | - Kevin McGrath
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Adam Slivka
- Department of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Graham M Snyder
- Department of Infection Prevention and Control, UPMC Presbyterian–Shadyside, Pittsburgh, Pennsylvania
- Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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Asadzadeh M, Alobaid K, Ahmad S, Mazloum S. First Report of Azole-Resistant Aspergillus fumigatus with TR 46/Y121F/T289A Mutations in Kuwait and an Update on Their Occurrence in the Middle East. J Fungi (Basel) 2023; 9:784. [PMID: 37623555 PMCID: PMC10455753 DOI: 10.3390/jof9080784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 07/17/2023] [Accepted: 07/18/2023] [Indexed: 08/26/2023] Open
Abstract
Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary aspergillosis (IPA) is a leading cause of death in immunocompromised patients, particularly those receiving chemotherapy and among bone marrow transplant recipients. Aspergillus fumigatus is the most prevalent causative agent and voriconazole is the first-line therapy for IPA. In this study, we report the first isolation of voriconazole-resistant A. fumigatus carrying TR46/Y121F/T289A mutations from an immunocompromised pregnant lady in Kuwait. The patient was successfully treated for a probable respiratory infection with caspofungin and voriconazole. The literature review from PubMed has identified itraconazole-resistant clinical and environmental A. fumigatus isolates with TR34/L98H mutations in the cyp51A from several Middle Eastern countries including Kuwait. However, clinical A. fumigatus isolates with cyp51A TR46/Y121F/T289A mutations have not been reported previously from any country in the region while environmental isolates have been reported only from Iran. The source of voriconazole-resistant A. fumigatus CYP51A TR46/Y121F/T289A mutant in our patient remained unknown. Surveillance for azole resistance among clinical and environmental isolates of A. fumigatus is warranted in Kuwait.
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Affiliation(s)
- Mohammad Asadzadeh
- Department of Microbiology, College of Medicine, Kuwait University, Safat 13110, Kuwait;
| | - Khaled Alobaid
- Mycology Reference Laboratory, Mubarak Al-Kabeer Hospital, Ministry of Health, Jabriya 46300, Kuwait;
| | - Suhail Ahmad
- Department of Microbiology, College of Medicine, Kuwait University, Safat 13110, Kuwait;
| | - Sara Mazloum
- Microbiology Laboratory, Jaber Al-Ahmad Hospital, Ministry of Health, South Surra 91711, Kuwait;
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Colaneri M, Giusti EM, Genovese C, Galli L, Lombardi A, Gori A. Mortality of Patients With Candidemia and COVID-19: A Systematic Review With Meta-analysis. Open Forum Infect Dis 2023; 10:ofad358. [PMID: 37520417 PMCID: PMC10375424 DOI: 10.1093/ofid/ofad358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Indexed: 08/01/2023] Open
Abstract
Mortality of candidemia in coronavirus disease 2019 (COVID-19) patients has not been deeply studied despite evidence suggesting an increased occurrence. We performed a systematic review and meta-analysis to summarize the available evidence about these patients' mortality and length of stay. Data about the in-hospital, all-cause and 30-day mortality, and length of stay were pooled. Subgroup analyses were performed to assess sources of heterogeneity. Twenty-six articles out of the 1915 records retrieved during the search were included in this review. The pooled in-hospital mortality was 62.62% (95% CI, 54.77% to 69.86%), while the mortality in intensive care unit (ICU) was 66.77% (95% CI, 57.70% to 74.75%). The pooled median in-hospital length of stay was 30.41 (95% CI, 12.28 to 48.55) days, while the pooled median length of stay in the ICU was 28.28 (95% CI, 20.84 to 35.73) days. The subgroup analyses did not identify the sources of heterogeneity in any of the analyses. Our results showed high mortality in patients with candidemia and COVID-19, suggesting the need to consider screening measures to prevent this life-threatening condition.
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Affiliation(s)
| | - Emanuele Maria Giusti
- EPIMED Research Center, Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Camilla Genovese
- Department of Clinical Sciences, Infectious Diseases and Immunopathology, Università di Milano, L. Sacco Hospital, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy
| | - Lucia Galli
- Department of Clinical Sciences, Infectious Diseases and Immunopathology, Università di Milano, L. Sacco Hospital, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy
| | - Andrea Lombardi
- Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy
- Infectious Diseases Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
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18
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Hariri G, Genoud M, Bruckert V, Chosidow S, Guérot E, Kimmoun A, Nesseler N, Besnier E, Daviaud F, Lagier D, Imbault J, Grimaldi D, Bouglé A, Mongardon N. Post-cardiac surgery fungal mediastinitis: clinical features, pathogens and outcome. Crit Care 2023; 27:6. [PMID: 36609390 PMCID: PMC9817255 DOI: 10.1186/s13054-022-04277-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 12/10/2022] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVES The occurrence of mediastinitis after cardiac surgery remains a rare and severe complication associated with poor outcomes. Whereas bacterial mediastinitis have been largely described, little is known about their fungal etiologies. We report incidence, characteristics and outcome of post-cardiac surgery fungal mediastinitis. METHODS Multicenter retrospective study among 10 intensive care units (ICU) in France and Belgium of proven cases of fungal mediastinitis after cardiac surgery (2009-2019). RESULTS Among 73,688 cardiac surgery procedures, 40 patients developed fungal mediastinitis. Five were supported with left ventricular assist device and five with veno-arterial extracorporeal membrane oxygenation before initial surgery. Twelve patients received prior heart transplantation. Interval between initial surgery and mediastinitis was 38 [17-61] days. Only half of the patients showed local signs of infection. Septic shock was uncommon at diagnosis (12.5%). Forty-three fungal strains were identified: Candida spp. (34 patients), Trichosporon spp. (5 patients) and Aspergillus spp. (4 patients). Hospital mortality was 58%. Survivors were younger (59 [43-65] vs. 65 [61-73] yo; p = 0.013), had lower body mass index (24 [20-26] vs. 30 [24-32] kg/m2; p = 0.028) and lower Simplified Acute Physiology Score II score at ICU admission (37 [28-40] vs. 54 [34-61]; p = 0.012). CONCLUSION Fungal mediastinitis is a very rare complication after cardiac surgery, associated with a high mortality rate. This entity should be suspected in patients with a smoldering infectious postoperative course, especially those supported with short- or long-term invasive cardiac support devices, or following heart transplantation.
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Affiliation(s)
- Geoffroy Hariri
- grid.462844.80000 0001 2308 1657Département d’anesthésie et réanimation, Institut de Cardiologie, GRC 29, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU DREAM, Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France ,grid.462844.80000 0001 2308 1657Institut Pierre Louis d’épidémiologie et de santé publique, Inserm U1136, Sorbonne Université, 75013 Paris, France
| | - Mathieu Genoud
- grid.150338.c0000 0001 0721 9812Service des urgences, Département de médecine aiguë, Hôpitaux Universitaires de Genève, 1205 Geneva, Switzerland
| | - Vincent Bruckert
- grid.462844.80000 0001 2308 1657Département d’anesthésie et réanimation, Institut de Cardiologie, GRC 29, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU DREAM, Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France ,grid.410528.a0000 0001 2322 4179Service d’anesthésie-réanimation, CHU de Nice, 06000 Nice, France
| | - Samuel Chosidow
- grid.412116.10000 0004 1799 3934Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94000 Créteil, France
| | - Emmanuel Guérot
- grid.414093.b0000 0001 2183 5849Médecine intensive-réanimation, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
| | - Antoine Kimmoun
- grid.29172.3f0000 0001 2194 6418CHRU de Nancy, Médecine intensive-réanimation Brabois, Inserm U1116, Université de Lorraine, 54000 Nancy, France
| | - Nicolas Nesseler
- grid.411154.40000 0001 2175 0984Service d’anesthésie-réanimation, CHU de Rennes, 35000 Rennes, France ,grid.410368.80000 0001 2191 9284CHU de Rennes, Inra, Inserm, Institut NUMECAN – UMR_A 1341, UMR_S 1241, CIC 1414 (Centre d’Investigation Clinique de Rennes), Univ Rennes, 35000 Rennes, France
| | - Emmanuel Besnier
- grid.41724.340000 0001 2296 5231Département d’anesthésie-réanimation, CHU de Rouen, 76000 Rouen, France ,grid.412043.00000 0001 2186 4076UNIROUEN, Inserm U1096, Normandie Univ, 76000 Rouen, France
| | - Fabrice Daviaud
- grid.417818.30000 0001 2204 4950Service de réanimation, Centre Cardiologique du Nord, 93200 Saint-Denis, France
| | - David Lagier
- grid.411266.60000 0001 0404 1115Service d’anesthésie réanimation 1, CHU la Timone, Assistance Publique-Hôpitaux de Marseille (AP-HM), 13000 Marseille, France
| | - Julien Imbault
- grid.42399.350000 0004 0593 7118Service d’anesthésie réanimation sud, centre médico-chirurgical Magellan, CHU de Bordeaux, 33600 Pessac, France ,grid.412041.20000 0001 2106 639XInserm, UMR 1034, Biology of Cardiovascular Diseases, Univ. Bordeaux, 33000 Bordeaux, France
| | - David Grimaldi
- Service de réanimation polyvalente, Hôpital Erasme, cliniques universitaires de Bruxelles, 1070 Brussels, Belgium
| | - Adrien Bouglé
- grid.462844.80000 0001 2308 1657Département d’anesthésie et réanimation, Institut de Cardiologie, GRC 29, Assistance Publique-Hôpitaux de Paris (AP-HP), DMU DREAM, Hôpital La Pitié-Salpêtrière, Sorbonne Université, 75013 Paris, France
| | - Nicolas Mongardon
- grid.412116.10000 0004 1799 3934Service d’anesthésie-réanimation chirurgicale, DMU CARE, DHU A-TVB, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94000 Créteil, France ,grid.428547.80000 0001 2169 3027U955-IMRB, Equipe 03 “Pharmacologie et Technologies pour les Maladies Cardiovasculaires (PROTECT)”, Inserm, Univ Paris Est Créteil (UPEC), Ecole Nationale Vétérinaire d’Alfort (EnVA), 94700 Maisons-Alfort, France ,grid.410511.00000 0001 2149 7878Faculté de Santé, Univ Paris Est Créteil, 94010 Créteil, France
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Xie M, Shao J, Wan Z, Yan T, Zhu S, Li S, Yu J. Detection of Candida DNA in peritoneal fluids by PCR assay optimizing the diagnosis and treatment for intra-abdominal candidiasis in high-risk ICU patients: A prospective cohort study. Front Microbiol 2023; 13:1070688. [PMID: 36687581 PMCID: PMC9849671 DOI: 10.3389/fmicb.2022.1070688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 12/12/2022] [Indexed: 01/06/2023] Open
Abstract
Background Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU). Methods A prospective single-center cohort study of surgical patients at high risk for IAC was conducted in the ICU. PF was collected from the abdominal drainage tubes (within 24 h) or by percutaneous puncture. Direct PF smear microscopy, PF culture, blood culture, and serum (1-3)-β-D-glucan were performed in all patients. For Candida PCR assay, the ITS1/ITS4 primers that targeted the ITS1-5.8 s-ITS2 regions were used for PCR, and sequencing analysis was used to identify the pathogen at the species level. IAC was defined according to the 2013 European consensus criteria. Results Among 83 patients at high risk for IAC, the IAC criteria were present in 17 (20.5%). The sensitivity and specificity of the Candida PCR assay were 64.7 and 89.4%, respectively, and the area under the receiver operating characteristic curve was 0.77 (95% CI: 0.63-0.91). In this cohort, the positive predictive value and negative predictive value were 90.8% (95% CI: 80.3-96.2%) and 61.1% (95% CI: 36.1-81.7%), respectively. Diagnostic consistency was moderate (kappa 0.529, p < 0.001) according to the 2013 European consensus criteria. Conclusion Detection of Candida DNA in PF using PCR can be considered an adjunct to existing routine diagnostic tools which may optimize the diagnosis and antifungal treatment of IAC in high-risk patients in the ICU.
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Affiliation(s)
- Min Xie
- Department of Critical Care Medicine, Peking University First Hospital, Peking University, Beijing, China
| | - Jin Shao
- Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China,Research Center for Medical Mycology, Peking University, Beijing, China,Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Peking University First Hospital, Beijing, China,National Clinical Research Center for Skin and Immune Diseases, Beijing, China,Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China
| | - Zhe Wan
- Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China,Research Center for Medical Mycology, Peking University, Beijing, China,Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Peking University First Hospital, Beijing, China,National Clinical Research Center for Skin and Immune Diseases, Beijing, China
| | - Ting Yan
- Department of Critical Care Medicine, Peking University First Hospital, Peking University, Beijing, China
| | - Sainan Zhu
- Department of Biostatistics, Peking University First Hospital, Peking University, Beijing, China
| | - Shuangling Li
- Department of Critical Care Medicine, Peking University First Hospital, Peking University, Beijing, China,*Correspondence: Shuangling Li, ✉
| | - Jin Yu
- Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China,Research Center for Medical Mycology, Peking University, Beijing, China,Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Peking University First Hospital, Beijing, China,National Clinical Research Center for Skin and Immune Diseases, Beijing, China,Jin Yu, ✉
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20
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Pokhrel S, Boonmee N, Tulyaprawat O, Pharkjaksu S, Thaipisutikul I, Chairatana P, Ngamskulrungroj P, Mitrpant C. Assessment of Biofilm Formation by Candida albicans Strains Isolated from Hemocultures and Their Role in Pathogenesis in the Zebrafish Model. J Fungi (Basel) 2022; 8:jof8101014. [PMID: 36294579 PMCID: PMC9605499 DOI: 10.3390/jof8101014] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 12/04/2022] Open
Abstract
Candida albicans, an opportunistic pathogen, has the ability to form biofilms in the host or within medical devices in the body. Biofilms have been associated with disseminated/invasive disease with increased severity of infection by disrupting the host immune response and prolonging antifungal treatment. In this study, the in vivo virulence of three strains with different biofilm formation strengths, that is, non-, weak-, and strong biofilm formers, was evaluated using the zebrafish model. The survival assay and fungal tissue burden were measured. Biofilm-related gene expressions were also investigated. The survival of zebrafish, inoculated with strong biofilms forming C. albicans,, was significantly shorter than strains without biofilms forming C. albicans. However, there were no statistical differences in the burden of viable colonogenic cell number between the groups of the three strains tested. We observed that the stronger the biofilm formation, the higher up-regulation of biofilm-associated genes. The biofilm-forming strain (140 and 57), injected into zebrafish larvae, possessed a higher level of expression of genes associated with adhesion, attachment, filamentation, and cell proliferation, including eap1, als3, hwp1, bcr1, and mkc1 at 8 h. The results suggested that, despite the difference in genetic background, biofilm formation is an important virulence factor for the pathogenesis of C. albicans. However, the association between biofilm formation strength and in vivo virulence is controversial and needs to be further studied.
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Affiliation(s)
- Sabi Pokhrel
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Nawarat Boonmee
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Orawan Tulyaprawat
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Sujiraphong Pharkjaksu
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Iyarit Thaipisutikul
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Phoom Chairatana
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Popchai Ngamskulrungroj
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Chalermchai Mitrpant
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Correspondence:
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21
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Giacobbe DR, Asperges E, Cortegiani A, Grecchi C, Rebuffi C, Zuccaro V, Scudeller L, Bassetti M. Performance of existing clinical scores and laboratory tests for the diagnosis of invasive candidiasis in critically ill, nonneutropenic, adult patients: a systematic review with qualitative evidence synthesis. Mycoses 2022; 65:1073-1111. [PMID: 35938455 DOI: 10.1111/myc.13515] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 08/03/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases in critically ill, adult patients. OBJECTIVES To summarize the available evidence on the diagnostic performance of clinical scores and laboratory tests for invasive candidiasis (IC) in nonneutropenic, adult critically ill patients. METHODS A systematic review was performed to evaluate studies assessing the diagnostic performance for IC of clinical scores and/or laboratory tests vs. a reference standard or a reference definition in critically ill, nonneutropenic, adult patients in ICU. RESULTS Clinical scores, despite the heterogeneity of study populations and IC prevalences, constantly showed a high negative predictive value (NPV) and a low positive predictive value (PPV) for the diagnosis of IC in the target population. Fungal antigen-based biomarkers (with most studies assessing serum beta-D-glucan) retained a high NPV similar to that of clinical scores, with a higher PPV, although the latter showed important heterogeneity across studies, possibly reflecting the targeted or untargeted use of these tests in patients with a consistent clinical picture and risk factors for IC. CONCLUSIONS Both clinical scores and laboratory tests showed high NPV for the diagnosis of IC in nonneutropenic critically ill patients. The PPV of laboratory tests varies significantly according to the baseline patients' risk of IC. This qualitative synthesis will provide the FUNDICU panel with baseline evidence to be considered during the development of definitions of IC in critically ill, nonneutropenic adult patients in ICU.
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Affiliation(s)
- Daniele Roberto Giacobbe
- Department of Health Sciences, University of Genoa, Genoa, Italy.,Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | - Erika Asperges
- Infectious Diseases Unit, IRCCS San Matteo, Pavia, Italy
| | - Andrea Cortegiani
- Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy.,Department of Anesthesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy
| | | | - Chiara Rebuffi
- Scientific Direction, IRCCS Istituto Giannina Gaslini, Scientific Direction, Italy
| | | | - Luigia Scudeller
- Research and Innovation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Bassetti
- Department of Health Sciences, University of Genoa, Genoa, Italy.,Clinica Malattie Infettive, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
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Early Empirical Anidulafungin Reduces the Prevalence of Invasive Candidiasis in Critically Ill Patients: A Case-control Study. J Crit Care Med (Targu Mures) 2022; 8:89-99. [PMID: 35950155 PMCID: PMC9097641 DOI: 10.2478/jccm-2022-0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 04/06/2022] [Indexed: 11/21/2022] Open
Abstract
Introduction Invasive candidiasis (IC) in critically ill patients is a serious infection with high rate of mortality. As an empirical therapy, like antibiotics, the use of antifungals is not common in intensive care units (ICUs) worldwide. The empirical use of echinocandins including anidulafungin is a recent trend. Aim of the study The objective of this study was to assess the impact of empirical anidulafungin in the development of invasive candidiasis in critically ill patients in ICU. Methods This retrospective case-control study was conducted on 149 patients with sepsis with/without septic shock and bacterial pneumonia. All the patients were divided into two groups. The ‘control group’ termed as ‘NEAT group’ received no empirical anidulafungin therapy and the ‘treated group’ termed as ‘EAT group’ received empirical anidulafungin therapy in early hospitalization hours. Results Seventy-two and 77 patients were divided into the control and the treated group, respectively. Patients in EAT group showed less incidences of IC (5.19%) than that of the NEAT group (29.17%) (p = 0.001). Here, the relative risk (RR) was 0.175 (95% CI, 0.064-0.493) and the risk difference (RD) rate was 24% (95% CI, 12.36%-35.58%). The 30-day all-cause mortality rate in NEAT group was higher (19.44%) than that of in EAT group (10.39%) (p = 0.04). Within the first 10-ICU-day, patients in the EAT group left ICU in higher rate (62.34%) than that in the NEAT group (54.17%). Conclusion Early empirical anidulafungin within 6 h of ICU admission reduced the risk of invasive candidiasis, 30-day all-cause mortality rate and increased ICU leaving rate within 10-day of ICU admission in critically ill patients.
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Abstract
Healthcare facilities require flexible layouts that can adapt quickly in the face of various disruptions. COVID-19 confirmed this need for both healthcare and manufacturing systems. Starting with the transfer of decision support systems from manufacturing, this paper generalizes layout re-design activities for complex systems by presenting a simulation framework. Through a real case study concerning the proliferation of nosocomial cross-infection in an intensive care unit (ICU), the model developed in systems dynamics, based on a zero order immediate logic, allows reproducing the evolution of the different agencies (e.g., physicians, nurses, ancillary workers, patients), as well as of the cyber-technical side of the ICU, in its general but also local aspects. The entire global workflow is theoretically founded on lean principles, with the goal of balancing the need for minimal patient throughput time and maximum efficiency by optimizing the resources used during the process. The proposed framework might be transferred to other wards with minimal adjustments; hence, it has the potential to represent the initial step for a modular depiction of an entire healthcare facility.
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Zakhem AE, Istambouli R, Jabbour JF, Hindy JR, Gharamti A, Kanj SS. Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients. Semin Respir Crit Care Med 2022; 43:46-59. [PMID: 35172358 DOI: 10.1055/s-0041-1741009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21-71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-β-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.
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Affiliation(s)
- Aline El Zakhem
- Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rachid Istambouli
- Leeds and York Partnership NHS Foundation Trust, Leeds, United Kingdom
| | - Jean-Francois Jabbour
- Department of Internal Medicine, Saint George Hospital University Medical Center, University of Balamand, Beirut, Lebanon
| | - Joya-Rita Hindy
- Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Amal Gharamti
- Department of Internal Medicine, Yale School of Medicine, Waterbury Hospital, Waterbury, Connecticut
| | - Souha S Kanj
- Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon
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Li Y, Liu Y, Sun Y, Ma S, Ma C, Zhou H, Chen G, Liu L, Cai D. Study on the mechanism of Yupingfeng powder in the treatment of immunosuppression based on UPLC⁃QTOF⁃MS, network pharmacology and molecular biology verification. Life Sci 2022; 289:120211. [PMID: 34875251 DOI: 10.1016/j.lfs.2021.120211] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 11/26/2021] [Accepted: 12/01/2021] [Indexed: 12/20/2022]
Abstract
AIMS The current study aims to investigate the effect of Yupingfeng (YPF) powder on immunosuppression, and explore the possible mechanisms. MAIN METHODS Firstly, the monomer components of YPF powder were analyzed by UPLC-QTOF-MS combined with UNIFI automatic analysis platform, then the mechanism of YPF on immunosuppressive treatment was investigated using network pharmacological method, and finally the prediction was verified in a Candida albicans (Can)-induced immunosuppressive BALB/c mouse model. KEY FINDINGS 98 monomer compounds in YPF were obtained. Through virtual analysis and screening on the oral utilization and drug likeness properties of the components, 47 effective components were got. 9 core targets obtained were enriched in IL-17 signaling pathway. In the mouse model, YPF could reduce the number of Can and alleviate Can-induced inflammation in the kidney effectively, upregulate Can-induced low proportion of CD4+/CD8+ of splenic lymphocytes, and increase Can-induced low activity of IL-17 pathway. SIGNIFICANCE These results demonstrate that YPF could improve the immunity of Can-induced immunosuppression in BALB/c mice through upregulating the activity of IL-17 pathway.
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Affiliation(s)
- Yuhua Li
- Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, PR China; Department of Pharmacy, the First Naval Force Hospital of Southern Theatre Command, Zhanjiang 524005, Guangdong, PR China
| | - Yongsheng Liu
- Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China
| | - Yang Sun
- Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China
| | - Shumei Ma
- State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 200437, PR China; Shanghai Professional and Technical Service Center for Biological Material Drug-ability Evaluation, Shanghai 200437, PR China
| | - Chunmei Ma
- State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 200437, PR China; Shanghai Professional and Technical Service Center for Biological Material Drug-ability Evaluation, Shanghai 200437, PR China
| | - Huiping Zhou
- Department of Pharmacy, the First Naval Force Hospital of Southern Theatre Command, Zhanjiang 524005, Guangdong, PR China
| | - Gui'e Chen
- Department of Pharmacy, the First Naval Force Hospital of Southern Theatre Command, Zhanjiang 524005, Guangdong, PR China
| | - Li Liu
- State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 200437, PR China; Shanghai Professional and Technical Service Center for Biological Material Drug-ability Evaluation, Shanghai 200437, PR China.
| | - De Cai
- Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, PR China.
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High risk and low prevalence diseases: Esophageal perforation. Am J Emerg Med 2021; 53:29-36. [PMID: 34971919 DOI: 10.1016/j.ajem.2021.12.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/23/2021] [Accepted: 12/07/2021] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Esophageal perforation is a rare but serious condition associated with a high rate of morbidity and mortality. OBJECTIVE This article highlights the pearls and pitfalls of esophageal perforation, including diagnosis, initial resuscitation, and management in the emergency department based on current evidence. DISCUSSION Esophageal perforation occurs with injury to the layers of the esophagus, resulting in mediastinal contamination and sepsis. While aspects of the history and physical examination may prompt consideration of the diagnosis, the lack of classic signs and symptoms cannot be used to rule out esophageal perforation. Chest radiograph often exhibits indirect findings suggestive of esophageal perforation, but these are rarely diagnostic. Advanced imaging is necessary to make the diagnosis, evaluate the severity of the injury, and guide appropriate management. Management focuses on hemodynamic stabilization with intravenous fluids and vasopressors if needed, gastric decompression, broad-spectrum antibiotics, and a thoughtful approach to airway management. Proton pump inhibitors and antifungals may be used as adjunctive therapies. Current available evidence for various treatment options (conservative, endoscopic, and surgical interventions) for esophageal perforation and resulting patient outcomes are limited. A multidisciplinary team approach with input from thoracic surgery, interventional radiology, gastroenterology, and critical care is recommended, with admission to the intensive care setting. CONCLUSIONS An understanding of esophageal perforation can assist emergency physicians in diagnosing and managing this deadly disease.
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Fisher J, Linder A, Calevo MG, Bentzer P. Non-corticosteroid adjuvant therapies for acute bacterial meningitis. Cochrane Database Syst Rev 2021; 11:CD013437. [PMID: 34813078 PMCID: PMC8610076 DOI: 10.1002/14651858.cd013437.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis. OBJECTIVES To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis. MAIN RESULTS We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events). AUTHORS' CONCLUSIONS Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
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Affiliation(s)
- Jane Fisher
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
| | - Adam Linder
- Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden
| | - Maria Grazia Calevo
- Epidemiology, Biostatistics Unit, IRCCS, Istituto Giannina Gaslini, Genoa, Italy
| | - Peter Bentzer
- Department of Anesthesiology and Intensive Care, Lund University, Lund, Sweden
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Candida Spp. in Lower Respiratory Tract Secretions - A Ten Years Retrospective Study. J Crit Care Med (Targu Mures) 2021; 7:217-226. [PMID: 34722925 PMCID: PMC8519383 DOI: 10.2478/jccm-2021-0016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/24/2021] [Indexed: 12/27/2022] Open
Abstract
Introduction Lower respiratory tract secretions (LRTS) like sputum and tracheal aspirates are frequently sent to the microbiology laboratory from patients with various respiratory pathologies. Improper collection techniques can lead to false-positive results, resulting in improper therapy. Aim of the study To determine the percentage of contaminated samples sent to the microbiology laboratory, to establish the prevalence of Candida spp. in non-contaminated samples and therefore, the presence of Candida spp. originating in lower respiratory tract infections. Material and Methods A 10-year data survey was conducted to assess the differences in Candida prevalence from contaminated versus non-contaminated samples, assessed and categorised by Bartlett grading system, and to emphasise the importance of quality control for potentially contaminated samples. The data were analysed according to gender, age, referring departments, and the species of Candida. For the statistical analysis, Kruskal-Wallis and Fisher tests were used, and the alpha value was set for 0.5. Results The prevalence of Candida spp. in all analysed samples was 31.60%. After excluding the contaminated samples, the actual prevalence was 27.66%. Of all sputum samples, 31.6% were contaminated. Patients aged more than 40 years old were more prone to provide contaminated sputum samples. C. albicans is more prevalent in non-contaminated sputum samples. In both sputum and tracheal aspirates, the chances of identifying a single species are higher than the chances of identifying multiple species. Conclusions The study emphasises the importance of assessing the quality of sputum samples because of the high number of improperly collected samples sent to the microbiology laboratory.
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Vannini M, Emery S, Lieutier-Colas F, Legueult K, Mondain V, Retur N, Gastaud L, Pomares C, Hasseine L. Epidemiology of candidemia in NICE area, France: A five-year study of antifungal susceptibility and mortality. J Mycol Med 2021; 32:101210. [PMID: 34768155 DOI: 10.1016/j.mycmed.2021.101210] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 09/27/2021] [Accepted: 10/06/2021] [Indexed: 01/27/2023]
Abstract
OBJECTIVES The aim of this study was to investigate the epidemiology of candidemia, the fungal susceptibility, the first-line therapy and the morality rate over 5 years. Knowing the differences of the yeasts in the candidemia local epidemiology, is essential to obtain information on fungal epidemiology to adapt antifungal strategies. MATERIALS/METHODS This retrospective study was conducted from January 2014 to December 2018. The susceptibility of the Candida strains were tested for amphotericin B, caspofungin, voriconazole and fluconazole. RESULTS The 304 strains were isolated from 290 patients (40 patients in 2014, 65 in 2015, 72 in 2016, 62 in 2017 and 51 in 2018). The three most common Candida spp isolated from blood cultures were Candida albicans (44%), Candida glabrata (22%) and Candida parapsilosis (13%). The proportion of non-albicans Candida decreased from 68% in 2014 to 45% in 2018. C. albicans and C. parapsilosis were to the four antifungals tested. As first-line therapy, 60% of patients received caspofungin and 26% fluconazole. There was no significant difference in the mortality between the two arms of patients (, 27% and 21%, p = 0.47 at 30 days respectively). Thirty day all-cause mortality was 31% and it decreased from 2014 (46%) to 2018 (18%). CONCLUSIONS We report that the absence of antifungal resistance of our C. albicans and C. parapsilosis candidemia suggests possible treatment after MALDI-TOF identification with fluconazole as first-line therapy in our hospital, as soon as possible and while continuing to perform the antifungal test.
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Affiliation(s)
- M Vannini
- Service de Parasitologie Mycologie, Centre Hospitalier Universitaire de NICE 06200, France
| | - S Emery
- Service de la Pharmacie Centre Hospitalier Universitaire de NICE 06200, France
| | - F Lieutier-Colas
- Service de la Pharmacie Centre Hospitalier Universitaire de NICE 06200, France
| | - K Legueult
- Service de Parasitologie Mycologie, Centre Hospitalier Universitaire de NICE 06200, France
| | - V Mondain
- Service d'Infectiologie, Centre Hospitalier Universitaire de NICE 06200, France
| | - N Retur
- Service de la Pharmacie Centre Hospitalier Universitaire de NICE 06200, France
| | - L Gastaud
- Unité de soins continus en hématologie, Centre Antoine Lacassagne, NICE 06000, France
| | - C Pomares
- Service de Parasitologie Mycologie, Centre Hospitalier Universitaire de NICE 06200, France; INSERM 1065 Equipe 6 C3M, Université Côte d'Azur, France
| | - L Hasseine
- Service de Parasitologie Mycologie, Centre Hospitalier Universitaire de NICE 06200, France.
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Tong Y, Zhang J, Wang L, Wang Q, Huang H, Chen X, Zhang Q, Li H, Sun N, Liu G, Zhang B, Song F, Alterovitz G, Dai H, Zhang L. Hyper-Synergistic Antifungal Activity of Rapamycin and Peptide-Like Compounds against Candida albicans Orthogonally via Tor1 Kinase. ACS Infect Dis 2021; 7:2826-2835. [PMID: 34514778 DOI: 10.1021/acsinfecdis.1c00448] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Candida albicans is a life-threatening, opportunistic fungal pathogen with a high mortality rate, especially within the immunocompromised populations. Multidrug resistance combined with limited antifungal drugs even worsens the situation. Given the facts that the current drug discovery strategies fail to deliver sufficient antifungals for the emerging multidrug resistance, we urgently need to develop novel approaches. By systematically investigating what caused the different antifungal activity of rapamycin in RPMI 1640 and YPD, we discovered that peptide-like compounds can generate a hyper-synergistic antifungal effect with rapamycin on both azole-resistant and sensitive clinical C. albicans isolates. The minimum inhibitory concentration (MIC) of rapamycin reaches as low as 2.14 nM (2-9 μg/mL), distinguishing this drug combination as a hyper-synergism by having a fractional inhibitory concentration (FIC) index ≤ 0.05 from the traditional defined synergism with an FIC index < 0.5. Further studies reveal that this hyper-synergism orthogonally targets the protein Tor1 and affects the TOR signaling pathway in C. albicans, very likely without crosstalk to the stress response, Ras/cAMP/PKA, or calcineurin signaling pathways. These results lead to a novel strategy of controlling drug resistant C. albicans infection in the immunocompromised populations. Instead of prophylactically administering other antifungals with undesirable side-effects for extended durations, we now only need to coadminister some nontoxic peptide additives. The novel antifungal strategy approached in this study not only provides a new therapeutic method to control fungal infections in rapamycin-taking immunocompromised patients but also mitigates the immunosuppressive side-effects of rapamycin, repurposing rapamycin as an antifungal agent with wide applications.
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Affiliation(s)
- Yaojun Tong
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Shanghai 200240, China
| | - Jingyu Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Luoqiang Wang
- Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing 100101, China
- Anhui University, Hefei 230601, China
| | - Qinqin Wang
- Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing 100101, China
| | - Huang Huang
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
| | - Xiangyin Chen
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Qing Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Hantian Li
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
| | - Nuo Sun
- Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC 20057, United States
| | - Guang Liu
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
| | | | - Fuhang Song
- Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing 100101, China
| | - Gil Alterovitz
- National Artificial Intelligence Institute, U.S. Department of Veterans Affairs, Washington, DC 20420, United States
| | - Huanqin Dai
- State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
| | - Lixin Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
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Ylipalosaari P, Ala‐Kokko TI, Koskenkari J, Laurila JJ, Ämmälä S, Syrjälä H. Use and outcome of empiric echinocandins in critically ill patients. Acta Anaesthesiol Scand 2021; 65:944-951. [PMID: 33481252 DOI: 10.1111/aas.13783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 12/16/2020] [Accepted: 12/28/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Echinocandins are recommended as a first-line empiric treatment for fungal infections of patients in an intensive care unit (ICU) with critical illness. The primary aim of the study was to compare outcomes among ICU patients treated with empiric anidulafungin (ANI), caspofungin (CASPO), or micafungin (MICA). METHODS A retrospective cohort study in a mixed adult ICU. Patient demographics, reason for ICU admission, ICU risk scores and organ support therapies were analyzed. Outcome parameters included ICU and hospital stay, 30-day mortality and 1-year mortality. RESULTS Empiric echinocandin therapy was given to 367 patients (ANI; 73 patients, CASPO; 84 patients, and MICA; 210 patients) with a median duration of 3 days in an ICU. Patient median age was 60.7 years. As a first-line therapy, 52% of patients received fluconazole. Positive Candida cultures were found in the following samples: blood, 16 (4.4%); central line, 27 (7.4%); deep site, 92 (25.1%). Median ICU stay (ANI 6.4 days, CASPO 5.3 days, MICA 8.1 days), hospital stay (ANI 33 days, CASPO 30 days, MICA 30 days), 30-day mortality (ANI 27%, CASPO 32%, MICA 32%), and 1-year mortality (ANI 33%, CASPO 44%, MICA 45%) did not differ between the groups . The cost of antifungal therapy during the ICU period was similar in the three echinocandin groups (ANI; €1 872, CASPO; €1 799, and MICA; €1783). CONCLUSION Our results show that ICU, hospital stay, and mortality (hospital, 30-day and 1-year) did not differ among patients with empiric anidulafungin, caspofungin, or micafungin treatment in a mixed adult ICU.
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Affiliation(s)
- Pekka Ylipalosaari
- Department of Infection Control Oulu University Hospital Medical Research Center Oulu University of Oulu Oulu Finland
| | - Tero I. Ala‐Kokko
- Division of Intensive Care Medicine Research Group of Surgery, Anesthesiology and Intensive Care Medicine Oulu University Hospital Medical Research Center Oulu University of Oulu Oulu Finland
| | - Juha Koskenkari
- Division of Intensive Care Medicine Research Group of Surgery, Anesthesiology and Intensive Care Medicine Oulu University Hospital Medical Research Center Oulu University of Oulu Oulu Finland
| | - Jouko J. Laurila
- Division of Intensive Care Medicine Research Group of Surgery, Anesthesiology and Intensive Care Medicine Oulu University Hospital Medical Research Center Oulu University of Oulu Oulu Finland
| | - Sirpa Ämmälä
- Hospital Pharmacy Oulu University Hospital Oulu Finland
| | - Hannu Syrjälä
- Department of Infection Control Oulu University Hospital Medical Research Center Oulu University of Oulu Oulu Finland
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Jamiu AT, Albertyn J, Sebolai OM, Pohl CH. Update on Candida krusei, a potential multidrug-resistant pathogen. Med Mycol 2021; 59:14-30. [PMID: 32400853 DOI: 10.1093/mmy/myaa031] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 04/09/2020] [Accepted: 04/14/2020] [Indexed: 12/19/2022] Open
Abstract
Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.
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Affiliation(s)
- A T Jamiu
- Pathogenic Yeast Research Group, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa, 9301
| | - J Albertyn
- Pathogenic Yeast Research Group, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa, 9301
| | - O M Sebolai
- Pathogenic Yeast Research Group, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa, 9301
| | - C H Pohl
- Pathogenic Yeast Research Group, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein, South Africa, 9301
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Boonsilp S, Homkaew A, Phumisantiphong U, Nutalai D, Wongsuk T. Species Distribution, Antifungal Susceptibility, and Molecular Epidemiology of Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand. J Fungi (Basel) 2021; 7:jof7070577. [PMID: 34356956 PMCID: PMC8303137 DOI: 10.3390/jof7070577] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/15/2021] [Accepted: 07/15/2021] [Indexed: 12/29/2022] Open
Abstract
Candida species represent a common cause of bloodstream infection (BSI). Given the emergence of non-albicans Candida (NAC) associated with treatment failure, investigations into the species distribution, fungal susceptibility profile, and molecular epidemiology of pathogens are necessary to optimize the treatment of candidemia and explore the transmission of drug resistance for control management. This study evaluated the prevalence, antifungal susceptibility, and molecular characteristics of Candida species causing BSI in a tertiary-level hospital in Bangkok, Thailand. In total, 54 Candida isolates were recovered from 49 patients with candidemia. C. tropicalis was the most prevalent species (33.3%), followed by C. albicans (29.6%). Most Candida species were susceptible to various antifungal agents, excluding C. glabrata and C. tropicalis, which had increased rates of non-susceptibility to azoles. Most C. glabrata isolates were non-susceptible to echinocandins, especially caspofungin. The population structure of C. albicans was highly diverse, with clade 17 predominance. GoeBURST analysis of C. tropicalis revealed associations between genotype and fluconazole resistance in a particular clonal complex. The population structure of C. glabrata appeared to have a low level of genetic diversity in MLST loci. Collectively, these data might provide a fundamental database contributing to the development of novel antifungal agents and diagnostic tests.
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Affiliation(s)
- Siriphan Boonsilp
- Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand;
- Correspondence: (S.B.); (T.W.)
| | - Anchalee Homkaew
- Division of Central Laboratory and Blood Bank, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand; (A.H.); (D.N.)
| | - Uraporn Phumisantiphong
- Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand;
- Division of Central Laboratory and Blood Bank, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand; (A.H.); (D.N.)
| | - Daranee Nutalai
- Division of Central Laboratory and Blood Bank, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand; (A.H.); (D.N.)
| | - Thanwa Wongsuk
- Department of Clinical Pathology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300, Thailand;
- Correspondence: (S.B.); (T.W.)
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Chen T, Malhotra P, Khameraj A, Ong-Bello N, Vyas PP, Rasul R, Schwartz RM, Farber BF. Cooling Blankets in Hospitalized Patients: Time to Reevaluate. Am J Med Sci 2021; 362:601-605. [PMID: 34161829 DOI: 10.1016/j.amjms.2021.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 05/07/2021] [Accepted: 06/18/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND The therapeutic benefits and rationale for treating fevers with external cooling methods remain unclear. We aimed to describe the clinical settings in which cooling blankets (CBs) are used. DESIGN We conducted a retrospective chart review of CB use in adult patients admitted to our tertiary care center over a one-year period. We measured how they are used and correlations between clinical variables and their duration of use. RESULTS 561 patients were included in our study. The mean highest temperature during hospitalization was 39.35°C (SD, 0.67). Shivering occurred in 176 patients (31.4%) while on a CB although 303 patients (54%) had no data regarding shivering. Discontinuation of CBs was recorded in only 177 (30.5%) cases. Among these, the median duration of use was 33.37 hours (IQR: 18.13-80.38) while the median duration of fever was 22.13 hours (IQR 6.67-51.98). Duration of CB use was highly correlated with fever duration (Spearman's rho, 0.771, p<.001), moderately with length of stay (LOS) (rho, 0.425, p<.001), LOS after CB initiation (rho, 0.475, p<.001) and antipyretic use (rho, 0.506, p<.001). No other statistically significant correlations were observed. CONCLUSION Documentation of CB use including temperature set points, time of discontinuation and duration in EMRs was poor. We could not establish benefits of CB use in this study but observed that almost a third of patients developed adverse effects in the form of shivering. Thus, adverse effects of CB use may outweigh potential benefits. Their use should be reevaluated and institutional protocols developed for their use.
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Affiliation(s)
- Thomas Chen
- Jane and Dayton Brown Division of Infectious Diseases at the Barbara and Donald Zucker School of Medicine at Northwell/Hofstra University, 400 Community Drive, Manhasset, NY 11030, United States.
| | - Prashant Malhotra
- Jane and Dayton Brown Division of Infectious Diseases at the Barbara and Donald Zucker School of Medicine at Northwell/Hofstra University, 400 Community Drive, Manhasset, NY 11030, United States.
| | - Aradhana Khameraj
- Department of Infection Prevention Northshore University Hospital, 300 Community Drive, Manhasset, NY 11030, United States.
| | - Nelda Ong-Bello
- Department of Infection Prevention Northshore University Hospital, 300 Community Drive, Manhasset, NY 11030, United States; Present affiliation and address: Department of Infection Prevention Glen Cove Hospital Northwell Health, 101 St Andrews Lane, Glen Cove, NY, United States
| | - Pooja P Vyas
- Hospitalist Division, Department of Internal Medicine Northwell Health Physician Partners, 300 Community Drive Manhasset, NY 11030; Present affiliation and address: Department of Internal Medicine Missouri Baptist Medical Center, 3032 N Ballas Road, St. Louis, MO 63131, United States.
| | - Rehana Rasul
- Biostatistics Unit, Feinstein Institute of Medical Research at Northwell Health, 175 Community Drive, Great Neck, NY 11021, United States.
| | - Rebecca M Schwartz
- Occupational Medicine, Epidemiology and Prevention, Zucker School of Medicine at Hofstra/Northwell Health, 175 Community Drive, Great Neck, NY 11021, United States.
| | - Bruce F Farber
- Jane and Dayton Brown Division of Infectious Diseases at the Barbara and Donald Zucker School of Medicine at Northwell/Hofstra University, 400 Community Drive, Manhasset, NY 11030, United States.
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Soulountsi V, Schizodimos T, Kotoulas SC. Deciphering the epidemiology of invasive candidiasis in the intensive care unit: is it possible? Infection 2021; 49:1107-1131. [PMID: 34132989 DOI: 10.1007/s15010-021-01640-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 06/08/2021] [Indexed: 12/12/2022]
Abstract
Invasive candidiasis (IC) has emerged in the last decades as an important cause of morbidity, mortality, and economic load in the intensive care unit (ICU). The epidemiology of IC is still a difficult and unsolved enigma for the literature. Accurate estimation of the true burden of IC is difficult due to variation in definitions and limitations inherent to available case-finding methodologies. Candidemia and intra-abdominal candidiasis (IAC) are the two predominant types of IC in ICU. During the last two decades, an increase in the incidence of candidemia has been constantly reported particularly in the expanding populations of elderly or immunosuppressed patents, with a parallel change in Candida species (spp.) distribution worldwide. Epidemiological shift in non-albicans spp. has reached worrisome trends. Recently, a novel, multidrug-resistant Candida spp., Candida auris, has globally emerged as a nosocomial pathogen causing a broad range of healthcare-associated invasive infections. Epidemiological profile of IAC remains imprecise. Though antifungal drugs are available for Candida infections, mortality rates continue to be high, estimated to be up to 50%. Increased use of fluconazole and echinocandins has been associated with the emergence of resistance to these drugs, which affects particularly C. albicans and C. glabrata. Crucial priorities for clinicians are to recognize the epidemiological trends of IC as well as the emergence of resistance to antifungal agents to improve diagnostic techniques and strategies, develop international surveillance networks and antifungal stewardship programmes for a better epidemiological control of IC.
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Affiliation(s)
- Vasiliki Soulountsi
- Department of Intensive Care Medicine, George Papanikolaou General Hospital, Thessaloniki, Greece.
| | - Theodoros Schizodimos
- Department of Intensive Care Medicine, George Papanikolaou General Hospital, Thessaloniki, Greece
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Saade A, Moratelli G, Dumas G, Mabrouki A, Tudesq JJ, Zafrani L, Azoulay E, Darmon M. Infectious events in patients with severe COVID-19: results of a cohort of patients with high prevalence of underlying immune defect. Ann Intensive Care 2021; 11:83. [PMID: 34036411 PMCID: PMC8148396 DOI: 10.1186/s13613-021-00873-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 05/10/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Empirical antibiotic has been considered in severe COVID-19 although little data are available regarding concomitant infections. This study aims to assess the frequency of infections, community and hospital-acquired infections, and risk factors for infections and mortality during severe COVID-19. METHODS Retrospective single-center study including consecutive patients admitted to the intensive care unit (ICU) for severe COVID-19. Competing-risk analyses were used to assess cumulative risk of infections. Time-dependent Cox and fine and gray models were used to assess risk factors for infections and mortality. Propensity score matching was performed to estimate the effect of dexamethasone. RESULTS We included 100 patients including 34 patients with underlying malignancies or organ transplantation. First infectious event was bacterial for 35 patients, and fungal for one. Cumulative incidence of infectious events was 27% [18-35] at 10 ICU-days. Prevalence of community-acquired infections was 7% [2.8-13.9]. Incidence density of hospital-acquired infections was 125 [91-200] events per 1000 ICU-days. Risk factors independently associated with hospital-acquired infections included MV. Patient's severity and underlying malignancy were associated with mortality. Dexamethasone was associated with increased infections (36% [20-53] vs. 12% [4-20] cumulative incidence at day-10; p = 0.01). After matching, dexamethasone was associated with hospital-acquired infections (35% [18-52] vs. 13% [1-25] at 10 days, respectively, p = 0.03), except in the subset of patients requiring MV, and had no influence on mortality. CONCLUSIONS In this population of COVID-19 patients with high prevalence of underlying immune defect, a high risk of infections was noted. MV and use of steroids were independently associated with infection rate.
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Affiliation(s)
- Anastasia Saade
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
- Université de Paris, ECSTRA Team, UMR 1153, Center of Epidemiology and Biostatistics, INSERM, Paris, France
| | - Giulia Moratelli
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
| | - Guillaume Dumas
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
- Université de Paris, ECSTRA Team, UMR 1153, Center of Epidemiology and Biostatistics, INSERM, Paris, France
| | - Asma Mabrouki
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
| | - Jean-Jacques Tudesq
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
| | - Lara Zafrani
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
- Université de Paris, ECSTRA Team, UMR 1153, Center of Epidemiology and Biostatistics, INSERM, Paris, France
| | - Elie Azoulay
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France
- Université de Paris, ECSTRA Team, UMR 1153, Center of Epidemiology and Biostatistics, INSERM, Paris, France
| | - Michael Darmon
- Service de médecine Intensive et de réanimation, hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France.
- Université de Paris, ECSTRA Team, UMR 1153, Center of Epidemiology and Biostatistics, INSERM, Paris, France.
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Gene expression profile and long noncoding RNA analysis in Candida albicans insoluble β-glucan-stimulated CD14 + monocytes and THP-1 cells. Microb Pathog 2021; 157:104963. [PMID: 34022361 DOI: 10.1016/j.micpath.2021.104963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 12/13/2022]
Abstract
Emerging evidence suggests that long noncoding RNAs (lncRNAs) play important roles in disease development. However, the roles of lncRNAs in the pathogenesis of Candida albicans (C. albicans) remain unclear. Our study aimed to investigate and characterize the mRNA and lncRNA transcriptomes of CD14+ monocytes and THP-1 cells stimulated with insoluble β-glucan by RNA-seq. We identified a total of 10788 differentially expressed (DE) mRNAs and 2021 DE lncRNAs in CD14+ monocytes, while 3349 DE mRNAs and 291 DE lncRNAs were observed in THP-1 cells. A total of 808 DE mRNAs and 51 DE lncRNAs overlapped between the two groups. We examined five collectively DE mRNAs and lncRNAs in both cells using quantitative real-time PCR, validating the reliability of the RNA-seq results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the 808 DE mRNAs were mostly enriched in the inflammatory response and NF-kappa B signaling pathway, respectively. Next, lncRNA-mRNA coexpression analysis was performed for the 51 DE lncRNAs and the 808 DE mRNAs in the two groups. We chose the common network pairs of the two groups to construct the coexpression network and revealed 97 network pairs comprising 8 dysregulated lncRNAs and 60 dysregulated mRNAs. We found that lncRNA lnc-CCL3L3-1:1 might be involved in the NF-kappa B signaling pathway in C. albicans infection. In conclusion, the aberrantly expressed lncRNAs might play a role in the pathogenesis of C. albicans infection and could be used as therapeutic targets in the future.
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Lotfali E, Fattahi A, Sayyahfar S, Ghasemi R, Rabiei MM, Fathi M, Vakili K, Deravi N, Soheili A, Toreyhi H, Shirvani F. A Review on Molecular Mechanisms of Antifungal Resistance in Candida glabrata: Update and Recent Advances. Microb Drug Resist 2021; 27:1371-1388. [PMID: 33956513 DOI: 10.1089/mdr.2020.0235] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Candida glabrata is the second frequent etiologic agent of mucosal and invasive candidiasis. Based on the recent developments in molecular methods, C. glabrata has been introduced as a complex composed of C. glabrata, Candida nivariensis, and Candida bracarensis. The four main classes of antifungal drugs effective against C. glabrata are pyrimidine analogs (flucytosine), azoles, echinocandins, and polyenes. Although the use of antifungal drugs is related to the predictable development of drug resistance, it is not clear why C. glabrata is able to rapidly resist against multiple antifungals in clinics. The enhanced incidence and antifungal resistance of C. glabrata and the high mortality and morbidity need more investigation regarding the resistance mechanisms and virulence associated with C. glabrata; additional progress concerning the drug resistance of C. glabrata has to be further prevented. The present review highlights the mechanism of resistance to antifungal drugs in C. glabrata.
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Affiliation(s)
- Ensieh Lotfali
- Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Fattahi
- Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shirin Sayyahfar
- Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Ghasemi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahdi Rabiei
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kimia Vakili
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Niloofar Deravi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirali Soheili
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Toreyhi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariba Shirvani
- Pediatric Infections Research Center, Research Institute for Children Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Bassetti M, Azoulay E, Kullberg BJ, Ruhnke M, Shoham S, Vazquez J, Giacobbe DR, Calandra T. EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group. Clin Infect Dis 2021; 72:S121-S127. [PMID: 33709127 DOI: 10.1093/cid/ciaa1751] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.
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Affiliation(s)
- Matteo Bassetti
- Infectious Diseases Unit, Ospedale Policlinico San Martino-IRCCS, Genoa, Italy.,Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Elie Azoulay
- Medical ICU, APHP, Saint-Louis Hospital, Paris, France.,Université de Paris, Paris, France
| | - Bart-Jan Kullberg
- Department of Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Markus Ruhnke
- Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine, Helios Klinikum Aue, Aue, Germany
| | - Shmuel Shoham
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jose Vazquez
- Department of Medicine, Division of Infectious Diseases, Medical College of Georgia/Augusta University, Augusta, Georgia, USA
| | | | - Thierry Calandra
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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Matos T, Lejko Zupanc T, Skofljanec A, Jazbec A, Matos E, Maver Vodičar P, Germ J, Ciglar T, Tomazin R, Kofol R, Mueller Premru M, Pirs M. Candidaemia in Central Slovenia: A 12-year retrospective survey. Mycoses 2021; 64:753-762. [PMID: 33786895 DOI: 10.1111/myc.13278] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Candida bloodstream infections (BSI) became an important invasive disease in the late 20th century, in particular among immunocompromised patients. Although considerable progress has been made in the management of patients with invasive mycoses, Candida BSI are still widespread among hospitalised patients and are associated with relatively high mortality. OBJECTIVES We conducted a retrospective study to evaluate patient characteristics, incidence, species distribution and antifungal susceptibility of BSI isolates of Candida spp. as well as outcomes of Candida BSI from 2001 to 2012, before the widespread use of echinocandins. This is the first epidemiological study of Candida BSI in Slovenia so far. METHODS All documented candidaemia cases from 2001 to 2012 in two major hospitals-University Medical Centre and Institute of Oncology in Ljubljana, Slovenia-were taken into consideration. Candida BSI were identified in 422 patients (250 male, 172 female). Laboratory and clinical data of these patients were retrospectively analysed. Mann-Whitney U test was used to compare continuous variables and Fisher's exact test or chi-squared test for categorical variables. RESULTS AND CONCLUSIONS The average incidence of Candida BSI was 0.524/10.000 patient-days (0,317/1000 admissions); 16/422 were younger than 1 year and 251/422 patients were over 60 years old. The most commonly isolated species were Candida albicans and Candida glabrata, followed by Candida parapsilosis. Majority of the patients had a single episode of Candida BSI, multiple episodes of Candida BSI occurred in 18/434 patients (4.1%); in 25/434 patients (5.8%) mixed Candida BSI were observed. Crude 30-day case-fatality rate was 55.4%.
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Affiliation(s)
- Tadeja Matos
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Tatjana Lejko Zupanc
- Department for Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
| | | | - Anja Jazbec
- University Medical Centre Ljubljana Division of Internal Medicine, Ljubljana, Slovenia
| | - Erika Matos
- Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Polona Maver Vodičar
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Julija Germ
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Tadeja Ciglar
- Department for Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Rok Tomazin
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Romina Kofol
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Manica Mueller Premru
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Mateja Pirs
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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41
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Amorim-Vaz S, Coste AT, Tran VDT, Pagni M, Sanglard D. Function Analysis of MBF1, a Factor Involved in the Response to Amino Acid Starvation and Virulence in Candida albicans. FRONTIERS IN FUNGAL BIOLOGY 2021; 2:658899. [PMID: 37744106 PMCID: PMC10512259 DOI: 10.3389/ffunb.2021.658899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 02/15/2021] [Indexed: 09/26/2023]
Abstract
Candida albicans is a commensal of human mucosae, but also one of the most common fungal pathogens of humans. Systemic infections caused by this fungus, mostly affecting immunocompromised patients, are associated to fatality rates as high as 50% despite the available treatments. In order to improve this situation, it is necessary to fully understand how C. albicans is able to cause disease and how it copes with the host defenses. Our previous studies have revealed the importance of the C. albicans gene MBF1 in virulence and ability to colonize internal organs of mammalian and insect hosts. MBF1 encodes a putative transcriptional regulator, and as such it likely has an impact in the regulation of C. albicans gene expression during host infection. Here, recent advances in RNA-seq technologies were used to obtain a detailed analysis of the impact of MBF1 on C. albicans gene expression both in vitro and during infection. MBF1 was involved in the regulation of several genes with a role in glycolysis and response to stress, particularly to nutritional stress. We also investigated whether an interaction existed between MBF1 and GCN4, a master regulator of response to starvation, and found that both genes were needed for resistance to amino acid starvation, suggesting some level of interaction between the two. Reinforcing this idea, we showed that the proteins encoded by both genes could interact. Consistent with the role of MBF1 in virulence, we also established that GCN4 was necessary for virulence in the mouse model of systemic infection as well as in the Galleria mellonella infection model.
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Affiliation(s)
- Sara Amorim-Vaz
- Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Alix T. Coste
- Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Van Du T. Tran
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Marco Pagni
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
| | - Dominique Sanglard
- Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
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Macauley P, Epelbaum O. Epidemiology and Mycology of Candidaemia in non-oncological medical intensive care unit patients in a tertiary center in the United States: Overall analysis and comparison between non-COVID-19 and COVID-19 cases. Mycoses 2021; 64:634-640. [PMID: 33608923 PMCID: PMC8013328 DOI: 10.1111/myc.13258] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/14/2021] [Accepted: 02/17/2021] [Indexed: 01/07/2023]
Abstract
The epidemiology and mycology of invasive candidiasis in the ICU is well‐described in certain types of critically ill patients but not in others. One population that has been scarcely studied is non‐neutropenic patients admitted specifically to medical ICUs. Even less is known about the broader category of medical ICU patients without active oncological disease. This group constitutes a very large share of the patients requiring critical care across the globe, especially in the era of the SARS‐CoV‐2 pandemic. We analysed medical ICU candidaemia episodes that occurred in non‐oncological patients in our tertiary academic centre in the United States from May 2014 to October 2020 to determine the incidence and species distribution of the associated isolates. We then separately considered non‐COVID‐19 and COVID‐19 cases and compared their characteristics. In the non‐COVID‐19 group, there were 38 cases for an incidence of 1.1% and rate of 11/1000 admissions. In the COVID‐19 group, there were 12 cases for an incidence of 5.1% and rate of 51/1000 admissions. In the entire sample, as well as separately in the non‐COVID‐19 and COVID‐19 groups,Candida albicans accounted for a minority of isolates. Compared to non‐COVID‐19 patients with candidaemia, COVID‐19 patients had lower ICU admission SOFA score but longer ICU length of stay and central venous catheter dwell time at candidaemia detection. This study provides valuable insight into the incidence and species distribution of candidaemia cases occurring in non‐oncological critically ill patients and identifies informative differences between non‐COVID‐19 and COVID‐19 patients.
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Affiliation(s)
- Precious Macauley
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, Valhalla, NY, USA
| | - Oleg Epelbaum
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, Valhalla, NY, USA
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43
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Belon L, Skidmore P, Mehra R, Walter E. Effect of a fever in viral infections — the ‘Goldilocks’ phenomenon? World J Clin Cases 2021; 9:296-307. [PMID: 33521098 PMCID: PMC7812885 DOI: 10.12998/wjcc.v9.i2.296] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 11/23/2020] [Accepted: 12/10/2020] [Indexed: 02/06/2023] Open
Abstract
Acute infections, including those due to Coronaviridae and other viruses, often stimulate a febrile response. A mild fever appears to improve outcome; it appears to diminish viral replication by several mechanisms, including virion entry into host cells and genome transcription, and improving host defence mechanisms against the pathogen. However, a fever may also damage host cellular and tissue function and increase metabolic demands. At temperatures at the lower end of the febrile range, the benefit of the fever appears to outweigh the detrimental effects. However, at higher temperatures, the outcome worsens, suggesting that the disadvantages of fever on the host predominate. A non-infective fever is associated with a worse outcome at lower temperatures, suggesting that hyperthermia carries less benefit in the absence of infection. This review discusses the risks and benefits of a fever on the host response, focusing on the effects of a fever on viral replication and host response, and the detrimental effect on the host.
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Affiliation(s)
- Lucas Belon
- Department of Intensive Care Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, Surrey, United Kingdom
| | - Peter Skidmore
- Department of General Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, Surrey, United Kingdom
| | - Rohan Mehra
- Department of General Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, Surrey, United Kingdom
| | - Edward Walter
- Department of Intensive Care Medicine, Royal Surrey County Hospital, Guildford GU2 7XX, Surrey, United Kingdom
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44
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Yan T, Li SL, Ou HL, Zhu SN, Huang L, Wang DX. Appropriate Source Control and Antifungal Therapy are Associated with Improved Survival in Critically Ill Surgical Patients with Intra-abdominal Candidiasis. World J Surg 2021; 44:1459-1469. [PMID: 31965275 DOI: 10.1007/s00268-020-05380-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in surgical intensive care patients. The purpose of this study was to investigate the impact of appropriate source control and antifungal therapy on the outcomes of critically ill surgical patients with IAC. METHODS This was a retrospective single-center cohort study. Adult surgical patients who were admitted to the intensive care unit and diagnosed with IAC from January 1, 2003, to December 31, 2016, were enrolled. The patients' data including risk factors of IAC, infection-related information, antifungal treatment and 30-day outcomes were collected. The primary endpoint was 30-day mortality. A COX proportional hazards model was used to analyze the association between appropriate treatment and 30-day survival. RESULTS A total of 82 patients were included in the analysis. Of these, 45 (54.9%) were complicated with septic shock at IAC diagnosis. Types of IAC included peritonitis (61.0%), intra-abdominal abscesses (23.2%) and biliary tract infections (15.9%). Of the included patients, 53 (64.6%) received appropriate source control and 44 (53.7%) appropriate antifungal therapy. Compared with patients with neither of these treatments, appropriate source control (HR 0.08, 95% CI 0.02-0.30; P < 0.001), appropriate antifungal therapy (HR 0.14, 95% CI 0.04-0.55; P = 0.005), and a combination of these treatments (HR 0.02, 95% CI 0.00-0.08; P < 0.001) were associated with reduced risk of death within 30 days after IAC diagnosis. CONCLUSION For critically ill surgical patients with IAC, both appropriate source control and appropriate antifungal therapy were associated with reduced risk of 30-day mortality, and the protective effects of the two appropriate treatments were additive.
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Affiliation(s)
- Ting Yan
- Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, No.8 Xishiku Street, Beijing, 100034, China
| | - Shuang-Ling Li
- Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, No.8 Xishiku Street, Beijing, 100034, China
| | - Hai-Li Ou
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Sai-Nan Zhu
- Department of Biostatistics, Peking University First Hospital, Beijing, China
| | - Lei Huang
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
| | - Dong-Xin Wang
- Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, No.8 Xishiku Street, Beijing, 100034, China.
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Ho J, Camilli G, Griffiths JS, Richardson JP, Kichik N, Naglik JR. Candida albicans and candidalysin in inflammatory disorders and cancer. Immunology 2021; 162:11-16. [PMID: 32880925 PMCID: PMC7730014 DOI: 10.1111/imm.13255] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/05/2020] [Accepted: 08/14/2020] [Indexed: 12/30/2022] Open
Abstract
As our understanding of mycology progresses, the impact of fungal microbes on human health has become increasingly evident. Candida albicans is a common commensal fungus that gives rise to local and systemic infections, particularly in immunocompromised patients where it can result in mortality. However, C. albicans has also been quietly linked with a variety of inflammatory disorders, to which it has traditionally been considered incidental; recent studies may now provide new aspects of these relationships for further consideration. This review provides a novel perspective on the impact of C. albicans and its peptide toxin, candidalysin, on human health, exploring their contributions to pathology within a variety of diseases.
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Affiliation(s)
- Jemima Ho
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
| | - Giorgio Camilli
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
| | - James S. Griffiths
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
| | - Jonathan P. Richardson
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
| | - Nessim Kichik
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
| | - Julian R. Naglik
- Centre for Host‐Microbiome InteractionsFaculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonLondonUK
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46
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Nguyen NZN, Tran VG, Lee S, Kim M, Kang SW, Kim J, Kim HJ, Lee JS, Cho HR, Kwon B. CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection. Immune Netw 2020; 20:e49. [PMID: 33425434 PMCID: PMC7779867 DOI: 10.4110/in.2020.20.e49] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/20/2020] [Accepted: 11/12/2020] [Indexed: 12/11/2022] Open
Abstract
C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5−/− mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5−/− mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.
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Affiliation(s)
- Nu Z N Nguyen
- BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea
| | - Vuvi G Tran
- BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea
| | - Saerom Lee
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Minji Kim
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Sang W Kang
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Juyang Kim
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Hye J Kim
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Jong S Lee
- Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Hong R Cho
- Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea.,Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
| | - Byungsuk Kwon
- BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea.,Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea
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47
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Wankap R, Mogo C, Niang M, Diallo A, Balloy L, Baes L, Collet L, Benoit-Cattin T, Permal S, Guegan H, Gangneux JP. Fungemia in the French department of Mayotte, Indian Ocean: A 10 years survey. J Mycol Med 2020; 31:101081. [PMID: 33360730 DOI: 10.1016/j.mycmed.2020.101081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/09/2020] [Accepted: 11/03/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE This study aimed at providing original data on fungemia in the Centre Hospitalier de Mayotte in terms of prevalence, epidemiological characteristics of infected patients, yeast species distribution and profile of in vitro antifungals susceptibility. METHODS A total of 223 positive blood cultures for yeasts were retrospectively reported during the period April 2010-April 2020. RESULTS Ninety-five episodes were identified corresponding to an incidence rate of 3.7 cases/100,000 inhabitants. The average age of patients was 33.5 years, and 63.3% patients were hospitalized in intensive care unit. The main co-morbidities were surgery in the 30 days prior to fungemia (27.8%), neoplasia (22.8%), parenteral nutrition (17.7%), diabetes (16.5%) and immunosuppressive medications (31.6%). Candida spp accounted for the majority of isolates (92.4%) with a predominance of non-albicans species (55.8% vs 33.7%), including C. albicans (33.7%), C. tropicalis (30.5%) and C. parapsilosis (20%). The antifungal susceptibility profiles did not differ from expected results for each species and did not change significantly over time. DISCUSSION Fungemia remain frequent hospital infections associated with high mortality in Mayotte. The vast majority of fungemia was due to Candida spp. Non-albicansCandida species reach half of the Candida isolates with a high percentage of C. tropicalis. Surprisingly, no case of candidemia due to C. glabrata were identified. The management of candidemia remains satisfactory and the treatment was adapted according to the international recommendations. However, the high susceptibility of Candida spp. isolates to fluconazole may invite to reconsider the use of this molecule as empirical and first-line treatment of candidemia in Mayotte.
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Affiliation(s)
- R Wankap
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte.
| | - C Mogo
- Suburban Hospital part of Johns Hopkins, Bethesda, MD, USA
| | - M Niang
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - A Diallo
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - L Balloy
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - L Baes
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - L Collet
- Centre Hospitalier de Mayotte, Laboratoire de Biologie Médicale, rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - T Benoit-Cattin
- Centre Hospitalier de Mayotte, Laboratoire de Biologie Médicale, rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - S Permal
- Centre Hospitalier de Mayotte, Service de Maladies infectieuses et de Médecine Interne, Université Rennes 1, Rue de l'hôpital, 97600 Mamoudzou, Mayotte
| | - H Guegan
- Centre Hospitalier Universitaire de Rennes, Service de Parasitologie-Mycologie, Rennes, France
| | - J P Gangneux
- Centre Hospitalier Universitaire de Rennes, Service de Parasitologie-Mycologie, Rennes, France
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48
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Evaluation of the prognostic factors for candidemia in a medical intensive care unit. JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.804426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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49
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Li D, Zhang J, Han W, Bai G, Cheng W, Cui N. Evaluation of the updated " Candida score" with Sepsis 3.0 criteria in critically ill patients. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:917. [PMID: 32953717 PMCID: PMC7475415 DOI: 10.21037/atm-20-995] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Background The Candida score proposed in 2009 was calculated on the definition of “severe sepsis”, which was removed in the Sepsis 3.0 definition. This study investigated the clinical relevance of Candida score with the updated Sepsis 3.0 definition (CS-3.0) instead of severe sepsis (CS-2009) in the new admitted critically ill patients. Methods We performed a retrospective analysis on a single center public database. All patients with ICU stay ≥72 hours were included in this study. The Candida score was calculated based on the data collected on ICU admission. The incidence of invasive candidiasis was determined and its relationship with the CS-2009 and CS-3.0 was studied. Results A total of 17,666 patients were identified after screening 58,976 hospital admissions, and 436 cases (2.5%) were diagnosed with invasive candidiasis. In the infection group, the number of patients who met the Sepsis 3.0 criteria was greater than the number of patients with severe sepsis (81.2% vs. 78.4%, P<0.005). The area under curve of the CS-2009 was 0.789 (95% CI: 0.765–0.813) and the CS-3.0 was 0.804 (95% CI: 0.782–0.827). Conclusions Our study confirmed the clinical relevance and comparative superiority of the updated Candida score model, using the Sepsis 3.0 definition, compared with the classic sepsis/severe sepsis model, in assessment of critically ill patients. Considering the clinical importance of organ dysfunction in ICI, the Sepsis 3.0 should be used as the basis for prediction of invasive candidiasis.
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Affiliation(s)
- Dongkai Li
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Jiahui Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Wen Han
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Guangxu Bai
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Wei Cheng
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Na Cui
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China
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50
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Choy A, Freedberg DE. Impact of microbiome-based interventions on gastrointestinal pathogen colonization in the intensive care unit. Therap Adv Gastroenterol 2020; 13:1756284820939447. [PMID: 32733601 PMCID: PMC7370550 DOI: 10.1177/1756284820939447] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 06/15/2020] [Indexed: 02/04/2023] Open
Abstract
In the intensive care unit (ICU), colonization of the gastrointestinal tract by potentially pathogenic bacteria is common and often precedes clinical infection. Though effective in the short term, traditional antibiotic-based decolonization methods may contribute to rising resistance in the long term. Novel therapies instead focus on restoring gut microbiome equilibrium to achieve pathogen colonization resistance. This review summarizes the existing data regarding microbiome-based approaches to gastrointestinal pathogen colonization in ICU patients with a focus on prebiotics, probiotics, and synbiotics.
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Affiliation(s)
| | - Daniel E. Freedberg
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA
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