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Recanatini C, van Werkhoven CH, van der Schalk TE, Paling F, Hazard D, Timbermont L, Torrens G, DiGiandomenico A, Esser MT, Wolkewitz M, Sifakis F, Goossens H, Bonten M, Oliver A, Malhotra-Kumar S, Kluytmans J. Impact of Pseudomonas aeruginosa carriage on intensive care unit-acquired pneumonia: a European multicentre prospective cohort study. Clin Microbiol Infect 2025; 31:433-440. [PMID: 39532190 DOI: 10.1016/j.cmi.2024.11.007] [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: 07/21/2024] [Revised: 10/27/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVES Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites. METHODS Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP. RESULTS A total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7-11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9-11.1) were independently associated with PAIP development. DISCUSSION PAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions.
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Affiliation(s)
- C Recanatini
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
| | - C H van Werkhoven
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - T E van der Schalk
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - F Paling
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - D Hazard
- Institute for Medical Biometry and Statistics, University Medical Centre Freiburg, Freiburg, Germany
| | - L Timbermont
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - G Torrens
- Servicio de Microbiología, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Centro de Investigación Biomédica en Red - Enfermedades Infecciosas (CIBERINFEC), Palma de Mallorca, Spain
| | - A DiGiandomenico
- Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - M T Esser
- Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA
| | - M Wolkewitz
- Institute for Medical Biometry and Statistics, University Medical Centre Freiburg, Freiburg, Germany
| | - F Sifakis
- AstraZeneca PLC, Department of US Medical Affairs, Gaithersburg, MD, USA; Department of Real-World Evidence, Gilead Sciences, Foster City, CA, USA
| | - H Goossens
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - M Bonten
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; European Clinical Research Alliance on Infectious Diseases, Utrecht, the Netherlands
| | - A Oliver
- Servicio de Microbiología, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Centro de Investigación Biomédica en Red - Enfermedades Infecciosas (CIBERINFEC), Palma de Mallorca, Spain
| | - S Malhotra-Kumar
- Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - J Kluytmans
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
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Renggli L, Burri A, Ehrhard S, Gasser M, Kronenberg A. Incidence and resistance rates of Pseudomonas aeruginosa bloodstream infections in Switzerland: a nationwide surveillance study (2010-2022). Infection 2025:10.1007/s15010-024-02452-1. [PMID: 39883261 DOI: 10.1007/s15010-024-02452-1] [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: 06/04/2024] [Accepted: 12/09/2024] [Indexed: 01/31/2025]
Abstract
PURPOSE Bloodstream infections (BSIs) cause significant morbidity and mortality worldwide. Pseudomonas aeruginosa is an important microorganism in BSIs. The aim of this study was to analyze recent trends in the incidence and resistance rates of P. aeruginosa BSIs in Switzerland and its different linguistic regions. METHODS This retrospective, nationwide observational study analyzed the incidence (using Poisson regression models) and antimicrobial resistance (using logistic regression models) of P. aeruginosa BSIs in Switzerland from 2010 to 2022. RESULTS The annual incidence of P. aeruginosa BSIs in Switzerland increased from 5.5 BSIs per 100,000 inhabitants in 2010 to 7.6 BSIs per 100,000 inhabitants in 2022 (p < 0.001). The incidence was higher in the French-speaking region than in the German-speaking region. The resistance rates increased significantly for cefepime (2.4% in 2010, 8.8% in 2022; p < 0.001), ceftazidime (5.6% in 2010, 9.4% in 2022; p = 0.014), ciprofloxacin (3.3% in 2010, 6.5% in 2022; p = 0.014), and piperacillin-tazobactam (6.4% in 2010, 11.2% in 2022; p = 0.002). No significant trends were observed for carbapenem-, aminoglycoside-, or multidrug-resistant P. aeruginosa. A high incidence was observed in patients ≥ 80 years, whereas resistance rates were high in young patients. CONCLUSION The increase in the incidence of P. aeruginosa BSIs emphasizes the importance of monitoring resistant and susceptible P. aeruginosa BSIs. Compared to the population-weighted mean resistance rates in Europe in 2022, those in Switzerland were lower, but an increase was observed for most antibiotics. The high resistance rates in young patients require further investigation.
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Affiliation(s)
- Luzia Renggli
- Swiss Centre for Antibiotic Resistance (ANRESIS), Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Andrea Burri
- Department of Internal Medicine, Solothurner Spitäler, Spital Dornach, Dornach, Switzerland.
- Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
| | - Simone Ehrhard
- Department of Emergency Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Michael Gasser
- Swiss Centre for Antibiotic Resistance (ANRESIS), Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Andreas Kronenberg
- Swiss Centre for Antibiotic Resistance (ANRESIS), Institute for Infectious Diseases, University of Bern, Bern, Switzerland
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Stimolo D, Budin M, De Mauro D, Suero E, Gehrke T, Citak M. Differences in microorganism profile in periprosthetic joint infections of the hip in patients affected by chronic kidney disease. J Orthop Traumatol 2024; 25:67. [PMID: 39702802 PMCID: PMC11659542 DOI: 10.1186/s10195-024-00806-x] [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: 07/15/2024] [Accepted: 11/07/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND Patients affected by chronic kidney disease (CKD) are at increased risk of periprosthetic joint infection (PJI) after total hip arthroplasty (THA). This patient population has a higher risk of recurrent infections and hospitalization. The aim of this study is to compare the profile of microorganisms in patients with CKD and PJI of the hip versus controls and to individuate potentially unusual and drug-resistant microorganisms among the causative bacteria. MATERIALS AND METHODS A total of 4261 patients affected by PJI of the hip were retrospectively studied. Patients affected by CKD in this population were identified and compared with a control group of patients with PJI but without CKD. Data on patient characteristics and comorbidities were collected. The microorganisms responsible for PJI were identified and compared between both groups. RESULTS The CKD group included 409 patients, 54.3% male, mean age of 73.8 ± 8.9 years, a higher body mass index (BMI) than the general population (29.88 ± 5.90 kg/m2), and higher age-adjusted CCI of 6.15 ± 2.35. Overall, 70 different isolates of microorganisms were identified, including 52 Gram-positive spp., 28 Gram-negative spp., 3 fungi, and 1 mycobacterium. Polymicrobial infections were more common in CKD group than controls (47.9% versus 30.9%; p < 0.0001). Staphylococcus spp. were the most common bacteria in both groups, followed by Gram-negative Enterobacteriaceae and Streptococcus spp. CKD group showed a higher risk of developing infections caused by Staphylococcus aureus (p = 0.003), Gram-negative bacteria, and Candida (p = 0.035). CONCLUSIONS Renal failure exposes patients who undergo THA to PJI caused by microorganisms that are potentially more drug resistant, leading to a higher risk of treatment failure. Knowing in advance the different microorganism profiles could help to plan a different surgical strategy.
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Affiliation(s)
- Davide Stimolo
- Helios ENDO-Klinik, Holstenstrasse 2, 22767, Hamburg, Germany.
- Musculoskeletal Oncology Unit, Department of Orthopedics, University of Florence, Largo Palagi 1, 50135, Florence, Italy.
| | - Maximilian Budin
- Helios ENDO-Klinik, Holstenstrasse 2, 22767, Hamburg, Germany
- Second Department, Orthopaedic Hospital Vienna-Speising, Speisinger Straße 109, 1130, Vienna, Austria
| | - Domenico De Mauro
- Helios ENDO-Klinik, Holstenstrasse 2, 22767, Hamburg, Germany
- Department of Public Health, Orthopedic Unit, "Federico II" University, Naples, Italy
- Department of Orthopedics and Geriatric Sciences, Catholic University of the Sacred Heart, Largo F. Vito 8, 00168, Rome, Italy
| | - Eduardo Suero
- Department of Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, Marchioninstrasse 15, 81377, Munich, Germany
| | - Thorsten Gehrke
- Helios ENDO-Klinik, Holstenstrasse 2, 22767, Hamburg, Germany
| | - Mustafa Citak
- Helios ENDO-Klinik, Holstenstrasse 2, 22767, Hamburg, Germany
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Valik JK, Giske CG, Hasan B, Gozalo-Margüello M, Martínez-Martínez L, Premru MM, Martinčič Ž, Beović B, Maraki S, Zacharioudaki M, Kofteridis D, McCarthy K, Paterson D, Cueto MD, Morales I, Leibovici L, Babich T, Granath F, Rodríguez-Baño J, Oliver A, Yahav D, Nauclér P. Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection. COMMUNICATIONS MEDICINE 2024; 4:264. [PMID: 39663376 PMCID: PMC11634891 DOI: 10.1038/s43856-024-00696-4] [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: 11/13/2023] [Accepted: 12/04/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited. METHODS We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia. Comprehensive clinical data and whole-genome sequencing of all bacterial strains were obtained. RESULTS Based on the virulence genotype, we identify several virulence clusters, each showing varying proportions of multidrug-resistant phenotypes. Genes tied to biofilm synthesis and epidemic clones ST175 and ST235 are associated with mortality, while the type III secretion system is associated with septic shock. Adding genomic biomarkers to machine learning models based on clinical data indicates improved prediction of severe outcomes in PA BSI patients. CONCLUSIONS These findings suggest that virulence markers provide prognostic information with potential applications in guiding adjuvant sepsis treatments.
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Affiliation(s)
- John Karlsson Valik
- Department of Medicine, Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden.
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
| | - Christian G Giske
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical microbiology, Karolinska University Hospital, Stockholm, Sweden
| | - Badrul Hasan
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Mónica Gozalo-Margüello
- Service of Microbiology. Hospital Universitario Marqués de Valdecilla. Instituto de Investigación Marqués de Valdecilla (IDIVAL), Cantabria, Spain
- CIBER de Enfermedades Infecciosas-CIBERINFEC (CB21/13/00068), Instituto de Salud Carlos III, Madrid, Spain
| | - Luis Martínez-Martínez
- Unit of Microbiology, University Hospital Reina Sofía, Córdoba, Spain
- Department of Agricultural Chemistry, Soil Science and Microbiology, University of Cordoba, Córdoba, Spain
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Žiga Martinčič
- Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Bojana Beović
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Sofia Maraki
- Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece
| | - Maria Zacharioudaki
- Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece
| | - Diamantis Kofteridis
- Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece
| | - Kate McCarthy
- Pathology Queensland, Royal Brisbane and Woman's Hospital, Brisbane, QLD, Australia
- University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia
| | - David Paterson
- University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia
| | - Marina de Cueto
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena / Departamentos de Medicina y Microbiología, Universidad de Sevilla, Sevilla, Spain
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Morales
- Servicio de Urgencias, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | - Leonard Leibovici
- Research Authority, Rabin Medical Center, Beilinson hospital, Petah-Tiqva, Israel
| | - Tanya Babich
- Research Authority, Rabin Medical Center, Beilinson hospital, Petah-Tiqva, Israel
| | - Fredrik Granath
- Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden
| | - Jesús Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena / Departamentos de Medicina y Microbiología, Universidad de Sevilla, Sevilla, Spain
- CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Antonio Oliver
- Servicio de Microbiología, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), CIBERINFEC, Palma de Mallorca, Spain
| | - Dafna Yahav
- Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel
| | - Pontus Nauclér
- Department of Medicine, Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
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Peirano G, Matsumara Y, Nobrega D, Church D, Pitout JDD. Population-based genomic surveillance of Pseudomonas aeruginosa causing bloodstream infections in a large Canadian health region. Eur J Clin Microbiol Infect Dis 2024; 43:501-510. [PMID: 38197977 DOI: 10.1007/s10096-024-04750-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/04/2024] [Indexed: 01/11/2024]
Abstract
PURPOSE Population-based surveillance was undertaken to determine clinical factors, susceptibility patterns, and incidence rates (IR) of Pseudomonas aeruginosa causing bloodstream infections (BSIs) in a Canadian region (2010-2018). METHODS We combined clinical data with genomics to characterize P. aeruginosa (BSIs) (n = 167) in a well-defined Canadian (Calgary) human population over a 9-year period (2010-2018). RESULTS The annual population IR per 100,000 patient years increased from 3.4/100,000 in 2010 to 5.9/100,000 in 2018, with the highest IRs in elderly males from the hospital setting. Over a quarter of patients presented with febrile neutropenia, followed by urinary tract infections and pneumonia. Antimicrobial resistance (AMR) rates and determinants were rare. The P. aeruginosa population was polyclonal consisting of three dominant sequence types (STs), namely ST244, ST111, and ST17. Antimicrobial-susceptible ST244 was the most common clone and belonged to three clades (A, B, C). The ST244 IR/100,000 increased over time due to the expansion of clade C. Multidrug-resistant ST111 was the second most common clone and IR/100,000 decreased over time. ST111 belonged to three clades (A, B, C) with clade C containing blaVIM-2. Different serotypes were linked to various STs. The IR/100,000 of P. aeruginosa that belonged to serotypes O6 increased significantly over time. CONCLUSION An effective multivalent vaccine consisting of five serotypes (O1, O3, O5, O6, O11) would confer protection to > 70% of Calgary residents with P. aeruginosa BSIs. This study has provided a unique perspective of the population dynamics over time of P. aeruginosa STs, clades, and serotypes responsible for BSIs.
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Affiliation(s)
- Gisele Peirano
- Cummings School of Medicine, University of Calgary, #9, 3535 Research Road NW, Calgary, Alberta, T2L 2K8, Canada
- Alberta Precision Laboratories, Calgary, Alberta, Canada
| | | | - Diego Nobrega
- Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Deirdre Church
- Cummings School of Medicine, University of Calgary, #9, 3535 Research Road NW, Calgary, Alberta, T2L 2K8, Canada
- Alberta Precision Laboratories, Calgary, Alberta, Canada
| | - Johann D D Pitout
- Cummings School of Medicine, University of Calgary, #9, 3535 Research Road NW, Calgary, Alberta, T2L 2K8, Canada.
- Alberta Precision Laboratories, Calgary, Alberta, Canada.
- University of Pretoria, Pretoria, Gauteng, South Africa.
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Nakashima H, Miyazaki M, Kuwamura T, Oda K, Haga Y, Imakyure O. Relationship between Target Time above Minimum Inhibitory Concentration Achievement Rate of Meropenem Using Monte Carlo Simulation and In-Hospital Survival in Patients with Pseudomonas aeruginosa Bacteremia. Antibiotics (Basel) 2024; 13:219. [PMID: 38534654 DOI: 10.3390/antibiotics13030219] [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: 01/24/2024] [Revised: 02/16/2024] [Accepted: 02/26/2024] [Indexed: 03/28/2024] Open
Abstract
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.
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Affiliation(s)
- Hajime Nakashima
- Department of Pharmacy, Japan Community Health Care Organization Kyushu Hospital, Fukuoka 806-0034, Japan
| | - Motoyasu Miyazaki
- Department of Pharmacy, Fukuoka University Chikushi Hospital, Fukuoka 818-8502, Japan
| | - Tsuneo Kuwamura
- Department of Pharmacy, Japan Community Health Care Organization Kurume General Hospital, Fukuoka 830-0013, Japan
| | - Kazutaka Oda
- Department of Pharmacy, Kumamoto University Hospital, Kumamoto 860-8556, Japan
| | - Yumi Haga
- Department of Clinical Laboratory, Japan Community Health Care Organization Kyushu Hospital, Fukuoka 806-0034, Japan
| | - Osamu Imakyure
- Department of Pharmacy, Fukuoka University Chikushi Hospital, Fukuoka 818-8502, Japan
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Sid Ahmed MA, Abdel Hadi H, Abu Jarir S, Ahmad Khan F, Arbab MA, Hamid JM, Alyazidi MA, Al-Maslamani MA, Skariah S, Sultan AA, Al Khal AL, Söderquist B, Ibrahim EB, Jass J, Ziglam H. Prevalence and microbiological and genetic characteristics of multidrug-resistant Pseudomonas aeruginosa over three years in Qatar. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2022; 2:e96. [PMID: 36483382 PMCID: PMC9726487 DOI: 10.1017/ash.2022.226] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/13/2022] [Accepted: 04/14/2022] [Indexed: 06/17/2023]
Abstract
OBJECTIVES Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. METHODS Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). RESULTS The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. CONCLUSIONS MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.
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Affiliation(s)
- Mazen A. Sid Ahmed
- Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
- The Life Science Centre – Biology, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Hamad Abdel Hadi
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sulieman Abu Jarir
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Faisal Ahmad Khan
- The Life Science Centre – Biology, School of Science and Technology, Örebro University, Örebro, Sweden
| | | | - Jemal M. Hamid
- Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Mohammed A. Alyazidi
- Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Muna A. Al-Maslamani
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sini Skariah
- Department of Microbiology and Immunology, Weill Cornell Medicine – Qatar, Doha, Qatar
| | - Ali A. Sultan
- Department of Microbiology and Immunology, Weill Cornell Medicine – Qatar, Doha, Qatar
| | - Abdul Latif Al Khal
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Bo Söderquist
- School of Medical Sciences, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Emad Bashir Ibrahim
- Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
- Biomedical Research Centre, Qatar University, Doha, Qatar
| | - Jana Jass
- The Life Science Centre – Biology, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Hisham Ziglam
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
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Martínez Pérez-Crespo PM, Rojas Á, Lanz-García JF, Retamar-Gentil P, Reguera-Iglesias JM, Lima-Rodríguez O, del Arco Jiménez A, Fernández Suárez J, Jover-Saenz A, Goikoetxea Aguirre J, León Jiménez E, Cantón-Bulnes ML, Ortega Lafont P, Armiñanzas Castillo C, Sevilla Blanco J, Cuquet Pedragosa J, Boix-Palop L, Becerril Carral B, Bahamonde-Carrasco A, Marrodan Ciordia T, Natera Kindelán C, Reche Molina IM, Herrero Rodríguez C, Pérez Camacho I, Vinuesa García D, Galán-Sánchez F, Smithson Amat A, Merino de Lucas E, Sánchez-Porto A, Guzmán García M, López-Hernández I, Rodríguez-Baño J, López-Cortés LE. Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort. Antibiotics (Basel) 2022; 11:antibiotics11060707. [PMID: 35740114 PMCID: PMC9220177 DOI: 10.3390/antibiotics11060707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/15/2022] [Accepted: 05/19/2022] [Indexed: 02/05/2023] Open
Abstract
Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients >14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60−79), 68.8% were male, median Charlson score was 5 (IQR 3−7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14−3.12)], haematological malignancy [2.45 (1.20−4.99)], obstructive uropathy [2.86 (1.13−3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10−10.92)] and healthcare-associated BSI [1.85 (1.13−3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ≥ 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.
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Affiliation(s)
- Pedro María Martínez Pérez-Crespo
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Nuestra Señora de Valme, 41014 Sevilla, Spain;
| | - Álvaro Rojas
- Departamento de Enfermedades Infecciosas del Adulto, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile;
| | - Joaquín Felipe Lanz-García
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
| | - Pilar Retamar-Gentil
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
| | - José María Reguera-Iglesias
- Servicio de Enfermedades Infecciosas, Hospital Regional Universitario de Málaga, IBIMA Málaga, 29010 Málaga, Spain;
| | - Olalla Lima-Rodríguez
- Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Álvaro Cunqueiro, 36312 Vigo, Spain;
| | - Alfonso del Arco Jiménez
- Grupo Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Costa del Sol, 29603 Marbella, Spain;
| | - Jonathan Fernández Suárez
- Unidad de Microbiología, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias, 33011 Oviedo, Spain;
| | - Alfredo Jover-Saenz
- Unidad Funcional de Infecciones Nosocomiales, Hospital Arnau de Vilanova, 25198 Lérida, Spain;
| | | | - Eva León Jiménez
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario Nuestra Señora de Valme, 41014 Sevilla, Spain;
| | | | - Pilar Ortega Lafont
- Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario de Burgos, 09006 Burgos, Spain;
| | - Carlos Armiñanzas Castillo
- Unidad de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, 39008 Santander, Spain;
| | - Juan Sevilla Blanco
- Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Jerez de la Frontera, 11407 Jerez de la Frontera, Spain;
| | - Jordi Cuquet Pedragosa
- Departamento de Medicina Interna, Hospital Universitario de Granollers, 08402 Granollers, Spain;
| | - Lucía Boix-Palop
- Unidad de Enfermedades Infecciosas, Hospital Universitari Mútua de Terrassa, 08221 Barcelona, Spain;
| | - Berta Becerril Carral
- Unidad Clínica de Gestión de Enfermedades Infecciosas y Microbiología, Área Sanitaria del Campo de Gibraltar, 11207 Cádiz, Spain;
| | | | - Teresa Marrodan Ciordia
- Departamento de Microbiología Clínica, Complejo Asistencial Universitario de León (CAULE), 24071 León, Spain;
| | - Clara Natera Kindelán
- Unidad Clínica de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain;
| | | | - Carmen Herrero Rodríguez
- Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología Clínica, Complejo Hospitalario de Jaén, 23007 Jaén, Spain;
| | - Inés Pérez Camacho
- Unidad de Medicina Tropical, Hospital General de Poniente, 04700 El Ejido, Spain;
| | - David Vinuesa García
- Unidad Gestión Clínica Enfermedades Infecciosas, Hospital Universitario Clínico San Cecilio, 18016 Granada, Spain;
| | - Fátima Galán-Sánchez
- Unidad de Gestión Clínica de Microbiología, Hospital Universitario Puerta del Mar, 11009 Cádiz, Spain;
| | - Alejandro Smithson Amat
- Unidad de Medicina Interna, Fundació Hospital de l’Esperit Sant, 08923 Santa Coloma de Gramenet, Spain;
| | - Esperanza Merino de Lucas
- Unidad de Enfermedades Infecciosas, Hospital Universitario General de Alicante, 03010 Alicante, Spain;
| | - Antonio Sánchez-Porto
- Unidad de Enfermedades Infecciosas y Microbiología, Hospital de la Línea de la Concepción, 11300 La Línea de la Concepción, Spain;
| | | | - Inmaculada López-Hernández
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
| | - Jesús Rodríguez-Baño
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
- Correspondence: ; Tel.: +34-660-839-073; Fax: +34-955-926-552
| | - Luis Eduardo López-Cortés
- Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen Macarena and Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla, 41009 Sevilla, Spain; (P.M.M.P.-C.); (J.F.L.-G.); (P.R.-G.); (I.L.-H.); (L.E.L.-C.)
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9
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Martak D, Gbaguidi-Haore H, Meunier A, Valot B, Conzelmann N, Eib M, Autenrieth IB, Slekovec C, Tacconelli E, Bertrand X, Peter S, Hocquet D, Guther J. High prevalence of Pseudomonas aeruginosa carriage in residents of French and German long-term care facilities. Clin Microbiol Infect 2022; 28:1353-1358. [PMID: 35597505 DOI: 10.1016/j.cmi.2022.05.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 04/22/2022] [Accepted: 05/03/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVES To determine prevalence, incidence, and factors associated with Pseudomonas aeruginosa (PA) intestinal carriage in residents of long-term care facilities (LTCFs) and to understand the population structure of this pathogen in LTCFs from two European countries. METHODS We assessed the prevalence of PA intestinal carriage and the incidence of acquisition by collecting fecal samples from 403 residents of 20 LTCFs. We collected 289 environmental samples from sinks and drinking water. Factors associated with carriage and acquisition of intestinal PA were identified. All PA isolates had their antibiotic phenotypic resistance profile determined and their genome sequenced, from which we assessed the population structure of the collection and identified resistance determinants. RESULTS We found a high proportion of residents with PA intestinal carriage (51.6%) over the entire study period. Over the follow-up period, 28.6% of the residents acquired intestinal PA. Older age (Odds ratio [OR] = 1.29, 95% confidence interval [CI]: 1.09-1.52; p = 0.002), urinary incontinence (OR = 2.56, 95% CI: 1.37-4.88; p = 0.003), and male gender (OR = 2.55), 95% CI: 1.05-6.18; p = 0.039) were associated with higher probability of carriage. Wheelchair usage (OR = 4.56, 95% CI: 1.38-15.05; p = 0.013) and a body mass index >25 (OR = 3.71, 95% CI: 1.17-11.82; p = 0.026) were associated with higher risk of PA acquisition. Population structure of our isolates was mainly non-clonal with 112 different STs among the 241 isolates. Most represented STs were high risk clones ST253 (n=26), ST17 (n=11), ST244 (n=11), ST309 (n=10), and ST395 (n=10). Most PA isolates (86.3%) were susceptible to antibiotics, with no acquired genes conferring resistance to antipseudomonal agents. CONCLUSIONS We found an unexpected high prevalence of PA intestinal carriage in LTCF residents mainly associated with individual-level factors. Our study revealed a polyclonal PA population structure suggesting that individual acquisition is more frequent than resident-to-resident transmission.
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Affiliation(s)
- Daniel Martak
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France.
| | - Houssein Gbaguidi-Haore
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France
| | - Alexandre Meunier
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France
| | - Benoit Valot
- UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France
| | - Nadine Conzelmann
- Infectious Diseases, Dept. of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany
| | - Michael Eib
- Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany
| | - Ingo B Autenrieth
- University Hospital Heidelberg, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany
| | - Céline Slekovec
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France
| | - Evelina Tacconelli
- Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy
| | - Xavier Bertrand
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France
| | - Silke Peter
- Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany
| | - Didier Hocquet
- Service d'Hygiène Hospitalière, Centre Hospitalier Universitaire, Besançon, France; UMR 6249 Chrono-environnement, CNRS, Université de Bourgogne Franche-Comté, Besançon, France; Centre de Ressources Biologiques - Filière Microbiologique de Besançon, Centre Hospitalier Universitaire, Besançon, France
| | - Julia Guther
- Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany
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10
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Esmaeilzadeh F, Mahmoodi S. A Novel Design of Multi-epitope Peptide Vaccine Against Pseudomonas
aeruginosa. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180818666211013110345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
As an opportunistic pathogen, Pseudomonas aeruginosa causes many different
hazardous infections. The high mortality rate resulting from infection with this antibiotic-resistant pathogen
has made it a major challenge in clinical treatment; it has been listed as the most harmful bacterium to
humans by the WHO. So far, no vaccine has been approved for P. aeruginosa.
Objective:
Infections performed by bacterial attachment and colonization with type IV pili (T4P), known
as the most essential adhesive vital for adhesion, while pilQ is necessary for the biogenesis of T4P, also
outer membrane proteins of a pathogen is also effective in stimulating the immune system; in this regard,
pilQ, OprF, and OprI, are excellent candidate antigens for production of an effective vaccine against P.
aeruginosa.
Methods:
In this research, various bioinformatics methods were employed in order to design a new multiepitope
peptide vaccine versus P. aeruginosa. Since T CD4+ cell immunity is important in eradicating P.
aeruginosa, OprF, OprI, and pilQ antigens were analyzed to determine Helper T cell Lymphocyte (HTL)
epitopes by many different immunoinformatics servers. One of the receptor agonists 2 (TLR2), a segment
of the Por B protein from Neisseria meningitides was used as an adjuvant in order to stimulate an effective
cellular immune response, and suitable linkers were used to connect all the above mentioned parts. In
the vaccine construct, linear B cell epitopes were also identified.
Results:
Conforming the bioinformatics forecasts, the designed vaccine possesses high antigenicity and is
not allergen.
Conclusion:
In this regard, the designed vaccine candidate is strongly believed to possess the potential of
inducing cellular and humoral immunity against P. aeruginosa.
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Affiliation(s)
| | - Shirin Mahmoodi
- Department of Medical Biotechnology,
School of Medicine, Fasa University of Medical Sciences, Fasa, Fars, Iran
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11
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Lynch JP, Zhanel GG. Pseudomonas aeruginosa Pneumonia: Evolution of Antimicrobial Resistance and Implications for Therapy. Semin Respir Crit Care Med 2022; 43:191-218. [PMID: 35062038 DOI: 10.1055/s-0041-1740109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Pseudomonas aeruginosa (PA), a non-lactose-fermenting gram-negative bacillus, is a common cause of nosocomial infections in critically ill or debilitated patients, particularly ventilator-associated pneumonia (VAP), and infections of urinary tract, intra-abdominal, wounds, skin/soft tissue, and bloodstream. PA rarely affects healthy individuals, but may cause serious infections in patients with chronic structural lung disease, comorbidities, advanced age, impaired immune defenses, or with medical devices (e.g., urinary or intravascular catheters, foreign bodies). Treatment of pseudomonal infections is difficult, as PA is intrinsically resistant to multiple antimicrobials, and may acquire new resistance determinants even while on antimicrobial therapy. Mortality associated with pseudomonal VAP or bacteremias is high (> 35%) and optimal therapy is controversial. Over the past three decades, antimicrobial resistance (AMR) among PA has escalated globally, via dissemination of several international multidrug resistant "epidemic" clones. We discuss the importance of PA as a cause of pneumonia including health care-associated pneumonia, hospital-acquired pneumonia, VAP, the emergence of AMR to this pathogen, and approaches to therapy (both empirical and definitive).
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Affiliation(s)
- Joseph P Lynch
- Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
| | - George G Zhanel
- Department of Medical Microbiology/Infectious Diseases, University of Manitoba, Max Rady College of Medicine, Winnipeg, Manitoba, Canada
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12
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Kishimoto K, Kasai M, Kawamura N, Otake S, Hasegawa D, Kosaka Y. Clinical characteristics and risk factors for mortality in children with Pseudomonas aeruginosa bacteraemia: A retrospective review at a paediatric tertiary centre. J Paediatr Child Health 2021; 57:1976-1980. [PMID: 34169605 DOI: 10.1111/jpc.15634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/08/2021] [Accepted: 06/16/2021] [Indexed: 11/29/2022]
Abstract
AIM The objective of this study was to describe clinical features and to assess the risk factors associated with mortality in Pseudomonas aeruginosa bacteraemia in a tertiary Japanese paediatric care hospital. METHODS Patients diagnosed with P. aeruginosa bacteraemia at our hospital between 2007 and 2018 were analysed in a retrospective case series. Inadequate initial therapy for P. aeruginosa bacteraemia was defined as initial treatment without antipseudomonal antibiotics or an administration of antipseudomonal agent to which the causative strain was resistant. Bacteraemia-related death was defined as all deaths occurring within 7 days after the onset of bacteraemia. RESULTS Overall, 41 patients with 42 P. aeruginosa bacteraemia episodes were identified. The most common underlying condition was malignancy (27%), followed by congenital heart disease (20%) and preterm birth (17%). Among the 42 P. aeruginosa clinical isolates, 24% were resistant to at least one of the antipseudomonal agents and 10% were resistant to more than one agent. The susceptibility levels for piperacillin, fourth-generation cephalosporins and ciprofloxacin were higher than that for carbapenems. Bacteraemia-related death was observed in 43% of episodes. The 30-day all-cause mortality was 50% (standard error 8%). Neonates, intensive care, mechanical ventilation, afebrile episodes, septic shock, hypoxia, renal injury and inadequate initial therapy were associated with bacteraemia-related death episodes. CONCLUSIONS We found that childhood P. aeruginosa bacteraemia is still a high mortality disease. Our results imply the importance of the identification of high-risk patients and the establishment of adequate empirical antibiotic therapy.
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Affiliation(s)
- Kenji Kishimoto
- Department of Hematology and Oncology, Children's Cancer Center, Kobe Children's Hospital, Kobe, Japan
| | - Masashi Kasai
- Department of Infectious Disease, Kobe Children's Hospital, Kobe, Japan
| | - Noriko Kawamura
- Department of Clinical Laboratory, Kobe Children's Hospital, Kobe, Japan
| | - Shogo Otake
- Department of Infectious Disease, Kobe Children's Hospital, Kobe, Japan
| | - Daiichiro Hasegawa
- Department of Hematology and Oncology, Children's Cancer Center, Kobe Children's Hospital, Kobe, Japan
| | - Yoshiyuki Kosaka
- Department of Hematology and Oncology, Children's Cancer Center, Kobe Children's Hospital, Kobe, Japan
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13
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Sid Ahmed MA, Hamid JM, Husain AA, Hadi HA, Skariah S, Sultan AA, Ibrahim EB, Al Khal AL, Soderquist B, Jass J, Omrani AS. Clinical outcomes, molecular epidemiology and resistance mechanisms of multidrug-resistant Pseudomonas aeruginosa isolated from bloodstream infections from Qatar. Ann Med 2021; 53:2345-2353. [PMID: 34882052 PMCID: PMC8667892 DOI: 10.1080/07853890.2021.2012588] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Bloodstream infections (BSIs) caused by multidrug-resistant (MDR)-Pseudomonas aeruginosa are associated with poor clinical outcomes, at least partly due to delayed appropriate antimicrobial therapy. The characteristics of MDR-P. aeruginosa bloodstream isolates have not been evaluated in Qatar. Our study aimed to examine in vitro susceptibility, clinical and molecular characteristics, and mechanisms of resistance of MDR-P. aeruginosa bloodstream isolates from Qatar. MATERIALS AND METHODS We included all MDR-P. aeruginosa isolated from blood cultures taken between October 2014 and September 2017. Blood cultures were processed using BD BACTEC™ FX automated system. BD Phoenix™ was used for identification, Liofilchem® MIC Test Strips for MIC determination. Whole-genome sequencing was performed using the Illumina-HiSeq-2000. RESULTS Out of 362 P. aeruginosa bloodstream isolates, 16 (4.4%) were MDR. The median patient age was 55 years (range 43-81) and all patients presented with septic shock. Most patients received meropenem (12/16) and/or colistin (10/16). Clinical response was achieved in eight patients, and five patients died within 30-days. MDR-P. aeruginosa isolates belonged to 13 different sequence types. All isolates were non-susceptible to cefepime and ciprofloxacin. The most active agents were colistin (16/16) and aztreonam (10/16). Seven isolates produced blaVIM, and four possessed genes encoding extended-spectrum β-lactamases. Aminoglycoside modifying enzymes were present in 15/16, transferable qnr-mediated quinolone resistance gene was detected in 3/16, and the novel ciprofloxacin modifying enzyme CrpP-encoding gene in one isolate. CONCLUSION MDR-P. aeruginosa BSIs are relatively uncommon in Qatar but are highly resistant, harbour multiple resistance genes, and are commonly associated with unfavourable clinical outcomes. Colistin was the only agent with consistent activity against the study isolates.Key messagesMDR-P. aeruginosa constituted <5% of P. aeruginosa blood isolates over three years.Typical risk factors for MDR infections were highly prevalent in the study population and overall clinical outcomes are consistent with those previously reported.Colistin was the only agent with consistent antibacterial activity against the study isolates.
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Affiliation(s)
- Mazen A Sid Ahmed
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar.,The Life Science Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Jemal M Hamid
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar
| | - Ahmed A Husain
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Hamad Abdel Hadi
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sini Skariah
- Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Ali A Sultan
- Department of Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Emad Bashir Ibrahim
- Department of Pathology and Laboratory Medicine, Division of Microbiology, Hamad Medical Corporation, Doha, Qatar.,Biomedical Research Centre, Qatar University, Doha, Qatar
| | - Abdul Latif Al Khal
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Bo Soderquist
- School of Medical Sciences, Faculty of Medicine and Health, Orebro University, Orebro, Sweden
| | - Jana Jass
- The Life Science Centre, School of Science and Technology, Örebro University, Örebro, Sweden
| | - Ali S Omrani
- Department of Medicine, Division of Infectious Diseases, Hamad Medical Corporation, Doha, Qatar.,Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
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14
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Kang JS, Moon C, Mun SJ, Lee JE, Lee SO, Lee S, Lee SH. Antimicrobial Susceptibility Trends and Risk Factors for Antimicrobial Resistance in Pseudomonas aeruginosa Bacteremia: 12-Year Experience in a Tertiary Hospital in Korea. J Korean Med Sci 2021; 36:e273. [PMID: 34751008 PMCID: PMC8575761 DOI: 10.3346/jkms.2021.36.e273] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 09/12/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) have been on the rise worldwide, and delayed active antimicrobial therapy is associated with high mortality. However, few studies have evaluated increases in P. aeruginosa infections with antimicrobial resistance and risk factors for such antimicrobial resistance in Korea. Here, we analyzed changes in antimicrobial susceptibility associated with P. aeruginosa bacteremia and identified risk factors of antimicrobial resistance. METHODS The medical records of patients with P. aeruginosa bacteremia who were admitted to a tertiary hospital between January 2009 and October 2020 were retrospectively reviewed. Antibiotic resistance rates were compared among the time periods of 2009-2012, 2013-2016, and 2017-2020 and between the intensive care unit (ICU) and non-ICU setting. Empirical antimicrobial therapy was considered concordant, if the organism was susceptible to antibiotics in vitro, and discordant, if resistant. RESULTS During the study period, 295 patients with P. aeruginosa bacteremia were identified. The hepatobiliary tract (26.8%) was the most common primary site of infection. The rates of carbapenem-resistant P. aeruginosa (CRPA), MDRPA, and extensively drug-resistant P. aeruginosa (XDRPA) were 24.7%, 35.9%, and 15.9%, respectively. XDRPA showed an increasing trend, and CRPA, MDRPA, and XDRPA were also gradually increasing in non-ICU setting. Previous exposure to fluoroquinolones and glycopeptides and urinary tract infection were independent risk factors associated with CRPA, MDRPA, and XDRPA. Previous exposure to carbapenems was an independent risk factor of CRPA. CRPA, MDRPA, and XDRPA were associated with discordant empirical antimicrobial therapy. CONCLUSION The identification of risk factors for antimicrobial resistance and analysis of antimicrobial susceptibility might be important for concordant empirical antimicrobial therapy in patients with P. aeruginosa bacteremia.
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Affiliation(s)
- Jin Suk Kang
- Division of Infectious Diseases, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Chisook Moon
- Division of Infectious Diseases, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
| | - Seok Jun Mun
- Division of Infectious Diseases, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Jeong Eun Lee
- Division of Infectious Diseases, Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Soon Ok Lee
- Division of Infectious Diseases, Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Shinwon Lee
- Division of Infectious Diseases, Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sun Hee Lee
- Division of Infectious Diseases, Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
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15
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Li J, Wei X, Hu Y, Gao Y, Zhang Y, Zhang X. A fluorescent nanobiocide based on ROS generation for eliminating pathogenic and multidrug-resistant bacteria. J Mater Chem B 2021; 9:3689-3695. [PMID: 33861292 DOI: 10.1039/d1tb00273b] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Exogenous reactive oxygen species (ROS) generation is a promising antibacterial strategy. The short diffusion distance coupled with the transient existence of ROS restrict their precise release at inflammation sites, so it is imperative to regulate the reactive sites of ROS donors. In this work, we developed a glycomimetic-decorated fluorescent nanobiocide to mediate the release of ROS generated from CuInS/ZnS quantum dots. The introduction of glycomimetics innovatively improved the biocompatibility of the hydrophobic quantum dots, allowing pathogenic bacteria to be targeted. The functionalized CuInS/ZnS quantum dots allowed simultaneous fluorescent reporting and sterilization under 660 nm illumination. Moreover, the nanobiocide can serve as a cell-binding glue causing bacterial aggregation, disrupting bacterial adhesion to host cells and inhibiting biofilm formation. Collectively, this work indicated the far-reaching future of ROS-generating biomimetic design for multifunctional nanobiocides to combat bacterial infections.
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Affiliation(s)
- Jie Li
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Xiaosong Wei
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Yuqing Hu
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Yingchao Gao
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Yufei Zhang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Xinge Zhang
- Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
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16
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MacKinnon MC, McEwen SA, Pearl DL, Lyytikäinen O, Jacobsson G, Collignon P, Gregson DB, Valiquette L, Laupland KB. Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study. BMC Infect Dis 2021; 21:606. [PMID: 34172003 PMCID: PMC8229717 DOI: 10.1186/s12879-021-06326-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 06/14/2021] [Indexed: 11/16/2022] Open
Abstract
Background Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. Methods During 2014–2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014–2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. Results From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. Conclusions In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06326-x.
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Affiliation(s)
- Melissa C MacKinnon
- Department of Population Medicine, University of Guelph, Guelph, Ontario, Canada.
| | - Scott A McEwen
- Department of Population Medicine, University of Guelph, Guelph, Ontario, Canada
| | - David L Pearl
- Department of Population Medicine, University of Guelph, Guelph, Ontario, Canada
| | - Outi Lyytikäinen
- Department of Health Security, National Institute for Health and Welfare, Helsinki, Finland
| | - Gunnar Jacobsson
- Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.,CARe - Center for Antibiotic Resistance Research, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - Peter Collignon
- Department of Infectious Disease and Microbiology, The Canberra Hospital, Garran, Australian Capital Territory, Australia.,Medical School, Australian National University, Acton, Australian Capital Territory, Australia
| | - Daniel B Gregson
- Departments of Medicine, and Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.,Alberta Health Services, Calgary Zone, Calgary, Alberta, Canada
| | - Louis Valiquette
- Department of Microbiology-Infectious Diseases, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Kevin B Laupland
- Department of Medicine, Royal Inland Hospital, Kamloops, British Columbia, Canada.,Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia
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17
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Antimicrobial Drug-Resistant Gram-Negative Saprophytic Bacteria Isolated from Ambient, Near-Shore Sediments of an Urbanized Estuary: Absence of β-Lactamase Drug-Resistance Genes. Antibiotics (Basel) 2020; 9:antibiotics9070400. [PMID: 32664302 PMCID: PMC7400359 DOI: 10.3390/antibiotics9070400] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/05/2020] [Accepted: 07/07/2020] [Indexed: 01/21/2023] Open
Abstract
We assessed the prevalence of antimicrobial resistance and screened for clinically relevant β-lactamase resistance determinants in Gram-negative bacteria from a large urbanized estuary. In contrast to the broad literature documenting potentially hazardous resistance determinants near wastewater treatment discharge points and other local sources of aquatic pollution, we employed a probabilistic survey design to examine ambient, near-shore sediments. We plated environmental samples from 40 intertidal and shallow subtidal areas around San Francisco Bay (California, USA) on drug-supplemented MacConkey agar, and we tested isolates for antimicrobial resistance and presence of clinically relevant β-lactamase resistance determinants. Of the 74 isolates identified, the most frequently recovered taxa were Vibrio spp. (40%), Shewanella spp. (36%), Pseudomonas spp. (11%), and Aeromonas spp. (4%). Of the 55 isolates tested for antimicrobial resistance, the Vibrio spp. showed the most notable resistance profiles. Most (96%) were resistant to ampicillin, and two isolates showed multidrug-resistant phenotypes: V. alginolyticus (cefotaxime, ampicillin, gentamicin, cefoxitin) and V. fluvialis (cefotaxime, ampicillin, cefoxitin). Targeted testing for class 1 integrons and presence of β-lactam-resistance gene variants TEM, SHV, OXA, CTX-M, and Klebsiella pneumonia carbapenemase (KPC) did not reveal any isolates harboring these resistance determinants. Thus, while drug-resistant, Gram-negative bacteria were recovered from ambient sediments, neither clinically relevant strains nor mobile β-lactam resistance determinants were found. This suggests that Gram-negative bacteria in this well-managed, urbanized estuary are unlikely to constitute a major human exposure hazard at this time.
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18
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Babich T, Naucler P, Valik JK, Giske CG, Benito N, Cardona R, Rivera A, Pulcini C, Fattah MA, Haquin J, MacGowan A, Grier S, Chazan B, Yanovskay A, Ami RB, Landes M, Nesher L, Zaidman-Shimshovitz A, McCarthy K, Paterson DL, Tacconelli E, Buhl M, Maurer S, Rodriguez-Bano J, Morales I, Oliver A, de Gopegui ER, Cano A, Machuca I, Gozalo-Marguello M, Martinez-Martinez L, Gonzalez-Barbera EM, Alfaro IG, Salavert M, Beovic B, Saje A, Mueller-Premru M, Pagani L, Vitrat V, Kofteridis D, Zacharioudaki M, Maraki S, Weissman Y, Paul M, Dickstein Y, Leibovici L, Yahav D. Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study. Int J Antimicrob Agents 2020; 55:105847. [PMID: 31770625 DOI: 10.1016/j.ijantimicag.2019.11.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 11/06/2019] [Accepted: 11/13/2019] [Indexed: 02/08/2023]
Abstract
This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving ≥48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01-1.03); female sex (1.34, 1.03-1.77); bedridden functional capacity (1.99, 1.24-3.21); recent hospitalisation (1.43, 1.07-1.92); concomitant corticosteroids (1.33, 1.02-1.73); and Charlson comorbidity index (1.05, 1.01-1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15-2.1), non-urinary source (2.44, 1.54-3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18-1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49-1.33). Among 2135 patients surviving ≥48 h, hospital-acquired infection (1.59, 1.21-2.09), baseline endotracheal tube (1.63, 1.13-2.36) and ICU admission (1.53, 1.02-2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection.
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Affiliation(s)
- Tanya Babich
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Pontus Naucler
- Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - John Karlsson Valik
- Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Christian G Giske
- Department of Laboratory Medicine, Karolinska Institutet and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
| | - Natividad Benito
- Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau-Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ruben Cardona
- Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Alba Rivera
- Department of Microbiology, Hospital de la Santa Creu i Sant Pau-Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain
| | - Celine Pulcini
- Université de Lorraine, APEMAC, F-54000 Nancy, France; Université de Lorraine, CHRU de Nancy, Infectious Diseases Department, F-54000 Nancy, France
| | - Manal Abdel Fattah
- Université de Lorraine, CHRU de Nancy, Infectious Diseases Department, F-54000 Nancy, France
| | - Justine Haquin
- Université de Lorraine, CHRU de Nancy, Infectious Diseases Department, F-54000 Nancy, France
| | - Alasdair MacGowan
- Department of Infection Sciences, Pathology Sciences Building, Southmead Hospital, Bristol, UK
| | - Sally Grier
- Department of Infection Sciences, Pathology Sciences Building, Southmead Hospital, Bristol, UK
| | - Bibiana Chazan
- Infectious Diseases Unit, Emek Medical Center, Afula, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Anna Yanovskay
- Infectious Diseases Unit, Emek Medical Center, Afula, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Ronen Ben Ami
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Infectious Diseases Unit, Sourasky Medical Center, Tel Aviv, Israel
| | - Michal Landes
- Infectious Diseases Unit, Sourasky Medical Center, Tel Aviv, Israel
| | - Lior Nesher
- Infectious Disease Institute, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheba, Israel
| | - Adi Zaidman-Shimshovitz
- Infectious Disease Institute, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheba, Israel
| | - Kate McCarthy
- UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia
| | - David L Paterson
- UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia
| | - Evelina Tacconelli
- Division of Infectious Diseases, Tübingen University Hospital, Tübingen, Germany
| | - Michael Buhl
- Division of Infectious Diseases, Tübingen University Hospital, Tübingen, Germany
| | - Susanna Maurer
- Division of Infectious Diseases, Tübingen University Hospital, Tübingen, Germany
| | - Jesus Rodriguez-Bano
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | - Isabel Morales
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | - Antonio Oliver
- Servicio de Microbiología & Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Illes Balears (IdISBa), Palma de Mallorca, Spain
| | - Enrique Ruiz de Gopegui
- Servicio de Microbiología & Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Illes Balears (IdISBa), Palma de Mallorca, Spain
| | - Angela Cano
- Infectious Diseases Unit, Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - Isabel Machuca
- Infectious Diseases Unit, Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | | | - Luis Martinez-Martinez
- Microbiology Service, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain
| | | | | | - Miguel Salavert
- Infectious Diseases Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Bojana Beovic
- Department of Infectious Diseases, University Medical Centre, Ljubljana, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Andreja Saje
- Department of Infectious Diseases, University Medical Centre, Ljubljana, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Manica Mueller-Premru
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Leonardo Pagani
- Infectious Diseases Unit, Annecy Genevois Hospital Center (CHANGE), Annecy, France
| | - Virginie Vitrat
- Infectious Diseases Unit, Annecy Genevois Hospital Center (CHANGE), Annecy, France
| | - Diamantis Kofteridis
- Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Maria Zacharioudaki
- Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Sofia Maraki
- Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Yulia Weissman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mical Paul
- Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel
| | - Yaakov Dickstein
- Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel
| | - Leonard Leibovici
- Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Dafna Yahav
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, 39 Jabotinsky Road, Petah Tikva 49100, Israel.
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19
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Zhao Y, Yu C, Yu Y, Wei X, Duan X, Dai X, Zhang X. Bioinspired Heteromultivalent Ligand-Decorated Nanotherapeutic for Enhanced Photothermal and Photodynamic Therapy of Antibiotic-Resistant Bacterial Pneumonia. ACS APPLIED MATERIALS & INTERFACES 2019; 11:39648-39661. [PMID: 31591880 DOI: 10.1021/acsami.9b15118] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Pseudomonas aeruginosa can cause a multitude of inflammations in humans. Due to its ability to form biofilm, the bacteria show durable resistance to drugs. Herein, we developed a heteromultivalent ligand-decorated nanotherapeutic inspired by living system for inhibition of antibiotic-resistant bacterial pneumonia. The nanotherapeutic with a heteromultivalent glycomimetic shell can specifically recognize P. aeruginosa to inhibit its biofilm formation and protect native cells from bacterial infection; the rate of biofilm inhibition was up to 85%. The nanotherapeutic with a bioresponsive hydrophobic core can protonate and control drug release in the microenvironment of bacterial infections. By utilizing these properties, the nanotherapeutics can effectively penetrate the internal structure of biofilms to release the drug, dispersing the biofilm by over 80% under laser irradiation. In vivo bioinspired nanotherapeutics have the potential to efficiently inhibit antibiotic-resistant P. aeruginosa-induced pneumonia. Collectively, we expect biomimicking systems to be the next generation of prevention and treatment as integrated antibacterial agents against P. aeruginosa.
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Affiliation(s)
- Yu Zhao
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Cong Yu
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Yunjian Yu
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Xiaosong Wei
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Xiaozhuang Duan
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Xijuan Dai
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
| | - Xinge Zhang
- Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry , Nankai University , Tianjin 300071 , China
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20
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Hagemann JB, Pfennigwerth N, Gatermann SG, von Baum H, Essig A. KPC-2 carbapenemase-producing Pseudomonas aeruginosa reaching Germany. J Antimicrob Chemother 2019; 73:1812-1814. [PMID: 29590370 DOI: 10.1093/jac/dky105] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 03/07/2018] [Indexed: 01/20/2023] Open
Abstract
Background Antimicrobial resistance due to carbapenemase expression poses a worldwide threat in healthcare. Inter-genus exchange of genetic information is of utmost importance in this context. Objectives Here, to the best of our knowledge, we describe the first detection and characterization of a KPC-2-producing Pseudomonas aeruginosa in Germany. Methods Characterization of the isolate was performed using MALDI-TOF MS, automated microdilution and MLST. Carbapenemase detection was performed using phenotypic and genotypic assays. The blaKPC-2-carrying plasmid was transformed into Escherichia coli NEB® 10-beta. The purified plasmid DNA was sequenced using the Illumina technique. Results The isolate expressed ST235 and was resistant to carbapenems. Antimicrobial susceptibility testing revealed colistin to be the only antimicrobial agent active in vitro. The blaKPC-2 gene was located on a replicon type lncHI1 plasmid as part of Tn4401. Conclusions The first detection (to the best of our knowledge) of plasmid-encoded KPC-2 in P. aeruginosa in Germany may point to a currently underestimated spread of carbapenemases among clinically relevant Gram-negative bacteria. Here, to the best of our knowledge, we also provide the first report of blaKPC-2 associated with the IncHI1 plasmid.
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Affiliation(s)
- Jürgen Benjamin Hagemann
- Institute of Medical Microbiology and Hygiene, University Hospital of Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
| | - Niels Pfennigwerth
- German National Reference Laboratory for Multidrug-Resistant Gram-negative Bacteria, Department of Medical Microbiology, Ruhr-University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
| | - Sören G Gatermann
- German National Reference Laboratory for Multidrug-Resistant Gram-negative Bacteria, Department of Medical Microbiology, Ruhr-University Bochum, Universitätsstraße 150, D-44801 Bochum, Germany
| | - Heike von Baum
- Institute of Medical Microbiology and Hygiene, University Hospital of Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
| | - Andreas Essig
- Institute of Medical Microbiology and Hygiene, University Hospital of Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
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21
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Pylaeva E, Bordbari S, Spyra I, Decker AS, Häussler S, Vybornov V, Lang S, Jablonska J. Detrimental Effect of Type I IFNs During Acute Lung Infection With Pseudomonas aeruginosa Is Mediated Through the Stimulation of Neutrophil NETosis. Front Immunol 2019; 10:2190. [PMID: 31572395 PMCID: PMC6749149 DOI: 10.3389/fimmu.2019.02190] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 08/30/2019] [Indexed: 12/18/2022] Open
Abstract
Pseudomonas aeruginosa is an opportunistic multidrug-resistant pathogen, able to grow in biofilms. It causes life-threatening complications in diseases characterized by the up-regulation of type I interferon (IFN) signaling, such as cancer or viral infections. Since type I IFNs regulate multiple functions of neutrophils, which constitute the first line of anti-bacterial host defense, in this work we aimed to study how interferon-activated neutrophils influence the course of P. aeruginosa infection of the lung. In lungs of infected IFN-sufficient WT mice, significantly elevated bacteria load was observed, accompanied by the prominent lung tissue damage. At the same time IFN-deficient animals seem to be partly resistant to the infection. Lung neutrophils from such IFN-deficient animals release significantly lower amounts of neutrophil extracellular traps (NETs) and reactive oxygen species (ROS), as compared to WT neutrophils. Of note, such IFN-deficient neutrophils show significantly decreased capacity to stimulate biofilm formation by P. aeruginosa. Reduced biofilm production impairs in turn the survival of bacteria in a lung tissue. In line with that, treatment of neutrophils with recombinant IFN-β enhances their NETosis and stimulates biofilm formation by Pseudomonas after co-incubation with such neutrophils. Possibly, bacteria utilizes neutrophil-derived NETs as a scaffold for released biofilms. In agreement with this, in vivo treatment with ROS-scavengers, NETs disruption or usage of the bacterial strains unable to bind DNA, suppress neutrophil-mediated biofilm formation in the lungs. Together, our findings indicate that the excessive activation of neutrophils by type I IFNs leads to their boosted NETosis that in turn triggers biofilm formation by P. aeruginosa and supports its persistence in the infected lung. Targeting these mechanisms could offer a new therapeutic approach to prevent persistent bacterial infections in patients with diseases associated with the up-regulation of type I IFNs.
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Affiliation(s)
- Ekaterina Pylaeva
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Sharareh Bordbari
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Ilona Spyra
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Anna Sophie Decker
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Susanne Häussler
- Molecular Bacteriology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
| | - Vadim Vybornov
- Institute for Astronomy and Astrophysics, Eberhard Karls University, Tübingen, Germany
| | - Stephan Lang
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
| | - Jadwiga Jablonska
- Translational Oncology, Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany
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22
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Rojas A, Palacios-Baena ZR, López-Cortés LE, Rodríguez-Baño J. Rates, predictors and mortality of community-onset bloodstream infections due to Pseudomonas aeruginosa: systematic review and meta-analysis. Clin Microbiol Infect 2019; 25:964-970. [PMID: 30995530 DOI: 10.1016/j.cmi.2019.04.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 03/25/2019] [Accepted: 04/05/2019] [Indexed: 12/01/2022]
Abstract
BACKGROUND Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional. OBJECTIVES To assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy. DATA SOURCE A systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases. Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered. INTERVENTION Empiric antimicrobial therapy for CO-BSI-PA. METHODS A systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model. RESULTS Twelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52-141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12-2.98l p 0.02). CONCLUSIONS CO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.
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Affiliation(s)
- A Rojas
- Departamento de Enfermedades Infecciosas del Adulto, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Z R Palacios-Baena
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | - L E López-Cortés
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.
| | - J Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
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López-Pintor JM, Navarro-San Francisco C, Sánchez-López J, García-Caballero A, Loza Fernández de Bobadilla E, Morosini MI, Cantón R. Direct antimicrobial susceptibility testing from the blood culture pellet obtained for MALDI-TOF identification of Enterobacterales and Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis 2019; 38:1095-1104. [DOI: 10.1007/s10096-019-03498-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 01/27/2019] [Indexed: 12/24/2022]
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Infections in Heart, Lung, and Heart-Lung Transplantation. PRINCIPLES AND PRACTICE OF TRANSPLANT INFECTIOUS DISEASES 2019. [PMCID: PMC7121494 DOI: 10.1007/978-1-4939-9034-4_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Half a century has passed since the first orthotopic heart transplant took place. Surgical innovations allowed for heart, lung, and heart-lung transplantation to save lives of patients with incurable chronic cardiopulmonary conditions. The complexity of the surgical interventions, chronic host health conditions, and antirejection immunosuppressive medications makes infectious complications common. Infections have remained one of the main barriers for successful transplantation and a source of significant morbidity and mortality. Recognition of infections and its management in this setting require outstanding clinical skills since transplant recipients may not exhibit classic signs or symptoms of disease, and laboratory work has some pitfalls. The prevention, identification, and management of infectious diseases complications in this population are a priority to undertake to improve the medical outcomes of transplantation. Herein, we reviewed the historical aspects, epidemiology, and prophylaxis of infections in heart, lung, and heart-lung transplantation. We also discuss the most prevalent organisms affecting the host and the organ systems involved.
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25
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Liu T, Zhang Y, Wan Q. Pseudomonas aeruginosa bacteremia among liver transplant recipients. Infect Drug Resist 2018; 11:2345-2356. [PMID: 30532566 PMCID: PMC6247952 DOI: 10.2147/idr.s180283] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Pseudomonas aeruginosa bacteremia remains as a life-threatening complication after liver transplantation (LT) and is intractable because of the high rate of drug resistance to commonly used antibiotics. To better understand the characteristics of this postoperative complication, PubMed and Embase searches as well as reference mining was done for relevant literature from the start of the databases through August 2018. Among LT recipients, the incidence of P. aeruginosa bacteremia ranged from 0.5% to 14.4% and mortality rates were up to 40%. Approximately 35% of all episodes of bloodstream infections (BSIs) were P. aeruginosa bacteremia, of which 47% were multidrug resistant and 63% were extensively drug resistant. Several factors are known to affect the mortality of LT recipients with P. aeruginosa bacteremia, including hypotension, mechanical ventilation, and increasing severity of illness. In LT recipients with P. aeruginosa bacteremia, alteration in DNA gyrase A genes and overexpression of proteins involved in efflux systems, namely the expression of KPC-2-type carbapenemase, NDM-1, and VIM-2-type MBL, contribute to the high resistance of P. aeruginosa to a wide variety of antibiotics. Because of complicated mechanisms of drug resistance, P. aeruginosa causes high morbidity and mortality in bacteremic LT patients. Consequently, early detection and treatment with adequate early targeted coverage for P. aeruginosa BSI are of paramount importance in the early posttransplantation period to obtain a better prognosis for LT patients.
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Affiliation(s)
- Taohua Liu
- Xiangya School of Medicine, Central South University, Changsha 410083, China
| | - Yuezhong Zhang
- Xiangya School of Medicine, Central South University, Changsha 410083, China
| | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China,
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26
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Merakou C, Schaefers MM, Priebe GP. Progress Toward the Elusive Pseudomonas aeruginosa Vaccine. Surg Infect (Larchmt) 2018; 19:757-768. [PMID: 30388058 DOI: 10.1089/sur.2018.233] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background: The gram-negative bacterial pathogen Pseudomonas aeruginosa causes a wide range of infections, mostly in hospitalized and immunocompromised patients, those with burns, surgical wounds, or combat-related wounds, and in people with cystic fibrosis. The increasing antibiotic resistance of P. aeruginosa confers a pressing need for vaccines, yet there are no P. aeruginosa vaccines approved for human use, and recent promising candidates have failed in large clinical trials. Discussion: In this review, we summarize recent clinical trials and pre-clinical studies of P. aeruginosa vaccines and provide a suggested framework for the makeup of a future successful vaccine. Murine models of infection suggest that antibodies, specifically opsonophagocytic killing antibodies (OPK), antitoxin antibodies, and anti-attachment antibodies, combined with T cell immunity, specifically TH17 responses, are needed for broad and potent protection against P. aeruginosa infection. A better understanding of the human immune response to P. aeruginosa infections, and to vaccine candidates, will eventually pave the way to a successful vaccine for this wily pathogen.
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Affiliation(s)
- Christina Merakou
- 1 Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital , Boston, Massachusetts.,2 Department of Anaesthesia, Harvard Medical School , Boston, Massachusetts
| | - Matthew M Schaefers
- 1 Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital , Boston, Massachusetts.,2 Department of Anaesthesia, Harvard Medical School , Boston, Massachusetts
| | - Gregory P Priebe
- 1 Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital , Boston, Massachusetts.,2 Department of Anaesthesia, Harvard Medical School , Boston, Massachusetts.,3 Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital , Boston, Massachusetts
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27
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Callejas-Díaz A, Fernández-Pérez C, Ramos-Martínez A, Múñez-Rubio E, Sánchez-Romero I, Vargas Núñez JA. Impact of Pseudomonas aeruginosa bacteraemia in a tertiary hospital: Mortality and prognostic factors. Med Clin (Barc) 2018; 152:83-89. [PMID: 29885868 DOI: 10.1016/j.medcli.2018.04.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 04/21/2018] [Accepted: 04/26/2018] [Indexed: 11/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Pseudomonas aeruginosa bacteraemia is associated with a very high mortality, conditioned by comorbidity, source, severity of the episode and lack of adequate treatment. The aim of the study is to know the mortality and prognostic factors of bacteraemia by P.aeruginosa in our hospital. PATIENTS AND METHODS We conducted a retrospective study of P.aeruginosa bacteraemia detected between 2009 and 2014. Epidemiological, clinical and microbiological characteristics were described. A risk factor analysis for mortality was performed. RESULTS We analysed 110 episodes of bacteraemia, which was more frequent in men of advanced age and with a history of hospitalisation, comorbidity and immunosuppression. Most of the bacteraemias were secondary (mainly of respiratory or urinary source) and led to a significant clinical deterioration. The presence of antibiotic resistance was very high, with 27.3% of multiresistant strains. Empirical treatment was adequate in 60.0% and 92.3% for definite treatment. Overall mortality was 37.3% and attributable mortality was 29.1%. The most important prognostic factors were Charlson index ≥3, history of haematologic malignancy, neutropenia and previous use of corticosteroids, source of bacteraemia, Pitt index ≥4, renal insufficiency, adequate definite treatment, empiric treatment with piperacillin/tazobactam in severe episodes and focus control. CONCLUSION P.aeruginosa bacteraemia is associated with a very high mortality, possibly more related to previous comorbidity and severity of the episode than to the treatment chosen. However, the main goal in management remains to optimise treatment, including focus control.
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Affiliation(s)
- Alejandro Callejas-Díaz
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España.
| | | | - Antonio Ramos-Martínez
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, España
| | - Elena Múñez-Rubio
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; Unidad de Enfermedades Infecciosas, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España
| | - Isabel Sánchez-Romero
- Servicio de Microbiología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España
| | - Juan Antonio Vargas Núñez
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, España; Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, España
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Wu PF, Lin YT, Wang FD, Yang TC, Fung CP. Is fluoroquinolone monotherapy a useful alternative treatment for Pseudomonas aeruginosa bacteraemia? Infection 2018; 46:365-373. [PMID: 29556979 DOI: 10.1007/s15010-018-1131-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 03/13/2018] [Indexed: 02/05/2023]
Abstract
PURPOSE Pseudomonas aeruginosa bacteraemia is associated with high mortality, and most monotherapies are beta-lactam-based. We aimed to investigate clinical outcomes of definitive fluoroquinolone monotherapy versus beta-lactam monotherapy for P. aeruginosa bacteraemia. METHODS This retrospective study enrolled adult patients receiving definitive monotherapy with beta-lactam or fluoroquinolone between November 2013 and November 2014 at Taipei Veterans General Hospital. The independent risk factors for 28-day mortality were analyzed by logistic regression and propensity score-adjusted analysis. RESULTS Among the 105 patients enrolled, 78 patients received beta-lactams and 27 received fluoroquinolones (20 with ciprofloxacin and 7 with levofloxacin). Primary bacteraemia (39.0%) and urinary tract infections (37.1%) were the most common sources of bacteraemia. The 28-day mortality rate was 11.1% for those receiving fluoroquinolones and 32.1% for those receiving beta-lactams (P = 0.062). The 28-day mortality rate between the two groups stratified by APACHE II and Pitt bacteraemia scores showed no significant differences in each category. Propensity score-adjusted multivariate analysis revealed that definitive therapy with a fluoroquinolone was not associated with 28-day mortality (OR 0.42; 95% CI 0.08-2.23; P = 0.305). CONCLUSIONS Fluoroquinolone might be an alternative to beta-lactam as a definitive monotherapy for P. aeruginosa bacteraemia provided they are active in vitro. Our results could be a basis for further studies and provide a possible target for antibiotic stewardship interventions in P. aeruginosa bacteraemia.
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Affiliation(s)
- Ping-Feng Wu
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan. .,Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Fu-Der Wang
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 112, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tsuey-Ching Yang
- Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chang-Phone Fung
- Division of Infectious Diseases, Sijhih Cathay General Hospital, New Taipei City, Taiwan
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29
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The Microbial Endocrinology of Pseudomonas aeruginosa: Inflammatory and Immune Perspectives. Arch Immunol Ther Exp (Warsz) 2018. [PMID: 29541797 DOI: 10.1007/s00005-018-0510-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Pseudomonas aeruginosa is a major pathogen responsible for both acute and chronic infection. Known as a colonising pathogen of the cystic fibrosis (CF) lung, it is implicated in other settings such as bronchiectasis. It has the ability to cause acute disseminated or localised infection particularly in the immunocompromised. Human hormones have been highlighted as potential regulators of bacterial virulence through crosstalk between analogous "quorum sensing" (QS) systems present in the bacteria that respond to mammalian hormones. Pseudomonas aeruginosa is known to utilise interconnected QS systems to coordinate its virulence and evade various aspects of the host immune system activated in response to infection. Several human hormones demonstrate an influence on P. aeruginosa growth and virulence. This inter-kingdom signalling, termed "microbial endocrinology" has important implications for host-microbe interaction during infection and, potentially opens up novel avenues for therapeutic intervention. This phenomenon, supported by the existence of sexual dichotomies in both microbial infection and chronic lung diseases such as CF is potentially explained by sex hormones and their influence on the infective process. This review summarises our current understanding of the microbial endocrinology of P. aeruginosa, including its endogenous QS systems and their intersection with human endocrinology, pathogenesis of infection and the host immune system.
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30
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Kuo G, Lu YA, Sun WC, Chen CY, Kao HK, Lin Y, Lee CH, Hung CC, Tian YC, Hsu HH. Epidemiology and outcomes of Endophthalmitis in chronic dialysis patients: a 13-year experience in a tertiary referral center in Taiwan. BMC Nephrol 2017; 18:270. [PMID: 28814278 PMCID: PMC5559798 DOI: 10.1186/s12882-017-0684-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Accepted: 08/05/2017] [Indexed: 11/10/2022] Open
Abstract
Background Endophthalmitis is a severe eye infection leading to disabling outcome. Because there were only a few case report illustrating endophthalmitis in chronic dialysis patient, we would like to investigate the epidemiology and clinical features of endophthalmitis in chronic dialysis patient in a tertiary referral center. Methods We searched the health information system in the study hospital with ICD9 encoding endophthalmitis during Jan. 2002 to Dec. 2015. A total of 32 episodes of endophthalmitis occurred in chronic dialysis patients. We performed an 1:2 case-control match on propensity score. The demographic features, clinical manifestation, infection focus and visual outcome were recorded. Results Of the total of 32 patients, 25 were classified as endogenous endophthalmitis and another seven were exogenous. Most patients presented with ophthalmalgia (n = 32, 100%) and periocular swelling (n = 31, 96.8%), whereas half of the patients suffered blurred vision (n = 16, 50%). Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent causative pathogens. Dialysis vascular infection was also a possible unique focus for bacteremia. The visual acuity of the endogenous groups were less likely to improve in the chronic dialysis patients compared with control group. Conclusion This is the first and the largest case series focusing on endophthalmitis in chronic dialysis patients. Our study showed different pathogen spectrum, an unique bacterial origin and worse visual outcome in these group of patients. Prompt referral to ophthalmologists when the patients present with suspicious symptoms (blurred vision, ophthalmalgia and periocular swelling) is crucial.
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Affiliation(s)
- George Kuo
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Yueh-An Lu
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Wei-Chiao Sun
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Chao-Yu Chen
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Huang-Kai Kao
- Department of Plastic and Reconstructive Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan
| | - YuJr Lin
- Center for Big Data Analytics and Statistics, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan
| | - Chia-Hui Lee
- Department of Pharmaceutical Materials Management, Taoyuan Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Cheng-Chieh Hung
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Ya-Chung Tian
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan
| | - Hsiang-Hao Hsu
- Department of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No.5 Fu-Shin Street, Kwei-shan, Taoyuan, 333, Taiwan.
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Piao Z, Yuan H. Osteopontin exacerbates Pseudomonas aeruginosa -induced bacteremia in mice. Cell Immunol 2017; 318:23-28. [DOI: 10.1016/j.cellimm.2017.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 04/25/2017] [Accepted: 05/24/2017] [Indexed: 11/28/2022]
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Hamaoka S, Naito Y, Katoh H, Shimizu M, Kinoshita M, Akiyama K, Kainuma A, Moriyama K, Ishii KJ, Sawa T. Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia. Microbiol Immunol 2017; 61:64-74. [PMID: 28370521 DOI: 10.1111/1348-0421.12467] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 01/16/2017] [Accepted: 01/19/2017] [Indexed: 11/27/2022]
Abstract
Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.
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Affiliation(s)
- Saeko Hamaoka
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Yoshifumi Naito
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Hideya Katoh
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Masaru Shimizu
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Mao Kinoshita
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Koichi Akiyama
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Atsushi Kainuma
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
| | - Kiyoshi Moriyama
- Department of Anesthesiology, School of Medicine, Kyorin University, Mitaka 181-8611, Japan
| | - Ken J Ishii
- Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.,Laboratory of Vaccine Science, Immunology Frontier Research Center, World Premier International Research Center, Osaka University, Suita, Osaka 565-0871, Japan
| | - Teiji Sawa
- Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of Pseudomonas aeruginosa bacteraemia: a retrospective cohort study. Eur J Clin Microbiol Infect Dis 2017; 36:1187-1196. [PMID: 28110415 PMCID: PMC5495847 DOI: 10.1007/s10096-017-2907-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Accepted: 01/09/2017] [Indexed: 10/31/2022]
Abstract
Ineffective antimicrobial therapy of Pseudomonas aeruginosa bacteraemia increases mortality. Recent studies have proposed the use of antimicrobial combination therapy composed of a beta-lactam with either ciprofloxacin or tobramycin. To determine if combination therapy correlates to lower mortality and is superior compared to monotherapy, we investigated the effect of antimicrobial treatment regimens on 30-day mortality in a cohort with Pseudomonas aeruginosa bacteraemia. All cases of P. aeruginosa bacteraemia (n = 292) in southwest Skåne County, Sweden (years 2005-2010, adult population 361,112) and the whole county (2011-2012, 966,130) were identified. Available medical and microbiological records for persons aged 18 years or more were reviewed (n = 235). Antimicrobial therapy was defined as empiric at admission or definitive after culture results and was correlated to 30-day mortality in a multivariate regression model. The incidence and mortality rates were 8.0 per 100,000 adults and 22.9% (67/292), respectively. As expected, multiple comorbidities and high age were associated with mortality. Adequate empiric or definitive antipseudomonal treatment was associated with lower mortality than other antimicrobial alternatives (empiric p = 0.02, adj. p = 0.03; definitive p < 0.001, adj. p = 0.007). No difference in mortality was seen between empiric antipseudomonal monotherapy or empiric combination therapy. However, definitive combination therapy including ciprofloxacin correlated to lower mortality than monotherapy (p = 0.006, adj. p = 0.003), whereas combinations including tobramycin did not. Our results underline the importance of adequate antipseudomonal treatment. These data also suggest that P. aeruginosa bacteraemia should be treated with an antimicrobial combination including ciprofloxacin when susceptible.
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Ishifuji T, Sando E, Kaneko N, Suzuki M, Kilgore PE, Ariyoshi K, Morimoto K, Hosokawa N, Yaegashi M, Aoshima M. Recurrent pneumonia among Japanese adults: disease burden and risk factors. BMC Pulm Med 2017; 17:12. [PMID: 28077107 PMCID: PMC5225545 DOI: 10.1186/s12890-016-0359-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 12/23/2016] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND In Japan and other societies with rapidly aging populations, recurrent pneumonia (RP) is a major clinical problem yet only limited information exists regarding the burden of this disease. METHODS A prospective study of adult pneumonia was conducted to investigate the incidence of RP and potential risk factors. From February 1, 2012 to January 31, 2013, patients aged ≥ 15 years who were diagnosed with pneumonia were prospectively enrolled in a representative community hospital located in central Japan. Patients were followed for one-year to evaluate the recurrence of pneumonia and characteristics associated with RP. Cox proportional hazards models were constructed to compute adjusted hazard ratios (aHR) and ascertain risk factors significantly associated with RP. RESULTS In total, 841 patients with a median age of 73 years (range 15-101 years) were enrolled totaling 1,048 person-years of observation with a median follow-up time of 475 days. A total of 137 patients had at least one recurrent episode with an incidence rate of 13.1 per 100 person-years (95% confidence interval: 11.1-15.5). In multivariate analysis, a past history of pneumonia (aHR 1.95, 95% CI: 1.35-2.8), chronic pulmonary disease (aHR 1.86, 1.24-2.78) and inhaled corticosteroid usage (aHR 1.78, 1.12-2.84) and hypnotic/sedative medication usage (aHR 2.06, 1.28-3.31) were identified as independent risk factors for recurrent pneumonia, whereas angiotensin converting enzyme-inhibitors usage was associated with a reduction of the risk of RP (aHR 0.22, 0.05-0.91). The detection of P. aeruginosa was significantly associated with RP even after adjusting for chronic pulmonary diseases (aHR = 2.37). CONCLUSIONS Recurrent pneumonia constitutes a considerable proportion of the pneumonia burden in Japan. A past history of pneumonia, chronic pulmonary disease, inhaled corticosteroid and hypnotic/sedative medication usage and detection of P. aeruginosa were identified as independent risk factors for recurrent pneumonia and special attention regarding the use of medications in this vulnerable population is needed to reduce the impact of this disease in aging populations.
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Affiliation(s)
- Tomoko Ishifuji
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852–8523, Japan
- Department of Clinical Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Eiichiro Sando
- Department of Clinical Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
- Department of General Internal Medicine, Kameda Medical Center, Kamogawa, Chiba Japan
| | - Norihiro Kaneko
- Department of Pulmonology, Kameda Medical Center, Kamogawa, Chiba Japan
| | - Motoi Suzuki
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852–8523, Japan
| | - Paul E. Kilgore
- Department of Family Medicine and Public Health Sciences, School of Medicine, Wayne State University, Michigan, USA
| | - Koya Ariyoshi
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852–8523, Japan
- Department of Clinical Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Konosuke Morimoto
- Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852–8523, Japan
| | - Naoto Hosokawa
- Department of Infectious Diseases, Kameda Medical Center, Kamogawa, Japan
| | - Makito Yaegashi
- Department of General Internal Medicine, Kameda Medical Center, Kamogawa, Chiba Japan
| | - Masahiro Aoshima
- Department of Pulmonology, Kameda Medical Center, Kamogawa, Chiba Japan
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McCarthy KL, Paterson DL. Community-acquired Pseudomonas aeruginosa bloodstream infection: a classification that should not falsely reassure the clinician. Eur J Clin Microbiol Infect Dis 2016; 36:703-711. [PMID: 27942878 DOI: 10.1007/s10096-016-2852-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 11/18/2016] [Indexed: 10/20/2022]
Abstract
Pseudomonas aeruginosa bloodstream infection (BSI) is predominantly acquired in the hospital setting. Community-onset infection is less common. Differences in epidemiology, clinical features, microbiological factors and BSI outcomes led to the separation of bacterial community-onset BSI into the categories of healthcare-associated infection (HCAI) and community-acquired infection (CAI). Community-acquired P. aeruginosa BSI epidemiology is not well defined in the literature. In addition, it is also not clear if the same factors separate CAI and HCAI BSI caused by P. aeruginosa alone. A retrospective multicentre cohort study was performed looking at P. aeruginosa BSI from January 2008 to January 2011. Strict definitions for HCAI and CAI were applied. Extensive epidemiological, clinical and outcome data were obtained. Thirty-four CAI episodes and 156 HCAI episodes were analysed. The CAI group could be characterised into seven distinct categories based on comorbidities and clinically suspected source of infection. A pre-morbidly healthy group could not be identified. On multivariate analysis, the presence of a rheumatological or a gastrointestinal comorbidity were significantly associated with CAI. There was no significant difference in length of stay or rates of mortality between HCAI or CAI. The clinician should not be falsely reassured regarding outcome by the diagnosis of a community-acquired P. aeruginosa BSI.
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Affiliation(s)
- K L McCarthy
- UQ Centre for Clinical Research, University of Queensland, Building 71/918, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, QLD, 4029, Australia.
| | - D L Paterson
- UQ Centre for Clinical Research, University of Queensland, Building 71/918, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, QLD, 4029, Australia
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Suzuki M, Satoh N, Nakamura M, Horita S, Seki G, Moriya K. Bacteremia in hemodialysis patients. World J Nephrol 2016; 5:489-496. [PMID: 27872830 PMCID: PMC5099594 DOI: 10.5527/wjn.v5.i6.489] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 09/05/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023] Open
Abstract
Infection is a common complication and is the second leading cause of death in hemodialysis patients. The risk of bacteremia in hemodialysis patients is 26-fold higher than in the general population, and 1/2-3/4 of the causative organisms of bacteremia in hemodialysis patients are Gram-positive bacteria. The ratio of resistant bacteria in hemodialysis patients compared to the general population is unclear. Several reports have indicated that hemodialysis patients have a higher risk of methicillin-resistant Staphylococcus aureus infection. The most common site of infection causing bacteremia is internal prostheses; the use of a hemodialysis catheter is the most important risk factor for bacteremia. Although antibiotic lock of hemodialysis catheters and topical antibiotic ointment can reduce catheter-related blood stream infection (CRBSI), their use should be limited to necessary cases because of the emergence of resistant organisms. Systemic antibiotic administration and catheter removal is recommended for treating CRBSI, although a study indicated the advantages of antibiotic lock and guidewire exchange of catheters over systemic antibiotic therapy. An infection control bundle recommended by the Center for Disease Control and Prevention succeeded in reducing bacteremia in hemodialysis patients with either a catheter or arteriovenous fistula. Appropriate infection control can reduce bacteremia in hemodialysis patients.
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Yoon YK, Kim HA, Ryu SY, Lee EJ, Lee MS, Kim J, Park SY, Yang KS, Kim SW. Tree-structured survival analysis of patients with Pseudomonas aeruginosa bacteremia: A multicenter observational cohort study. Diagn Microbiol Infect Dis 2016; 87:180-187. [PMID: 27863948 DOI: 10.1016/j.diagmicrobio.2016.10.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 09/13/2016] [Accepted: 10/03/2016] [Indexed: 11/20/2022]
Abstract
This study aimed to construct a prediction algorithm, which is readily applicable in the clinical setting, to determine the mortality rate for patients with P. aeruginosa bacteremia. A multicenter observational cohort study was performed retrospectively in seven university-affiliated hospitals in Korea from March 2012 to February 2015. In total, 264 adult patients with monomicrobial P. aeruginosa bacteremia were included in the analyses. Among the predictors independently associated with 30-day mortality in the Cox regression model, Pitt bacteremia score >2 and high-risk source of bacteremia were identified as critical nodes in the tree-structured survival analysis. Particularly, the empirical combination therapy was not associated with any survival benefit in the Cox regression model compared to the empirical monotherapy. This study suggests that determining the infection source and evaluating the clinical severity are critical to predict the clinical outcome in patients with P. aeruginosa bacteremia.
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Affiliation(s)
- Young Kyung Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University Anam Hospital
| | - Hyun Ah Kim
- Division of Infectious Diseases, Department of Internal Medicine, Keimyung University Dongsan Hospital
| | - Seong Yeol Ryu
- Division of Infectious Diseases, Department of Internal Medicine, Keimyung University Dongsan Hospital
| | - Eun Jung Lee
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital
| | - Mi Suk Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Medical Center
| | - Jieun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Hanyang University Kuri Hospital
| | - Seong Yeon Park
- Division of Infectious Diseases, Department of Internal Medicine, Dongguk University Ilsan Hospital
| | - Kyung Sook Yang
- Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital
| | - Shin Woo Kim
- Department of Biostatistics, Korea University College of Medicine, Republic of Korea.
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Hammer KL, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Differential effect of prior β-lactams and fluoroquinolones on risk of bloodstream infections secondary to Pseudomonas aeruginosa. Diagn Microbiol Infect Dis 2016; 87:87-91. [PMID: 27810318 DOI: 10.1016/j.diagmicrobio.2016.09.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 09/15/2016] [Accepted: 09/20/2016] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This retrospective case-control study examines risk factors for bloodstream infections (BSI) due to Pseudomonas aeruginosa (PSA). METHODS Hospitalized adults with Gram-negative BSI at Palmetto Health from 2010 to 2015 were identified. Multivariate logistic regression was used to examine PSA BSI risk factors. RESULTS Seventy and 910 patients with PSA and Enterobacteriaceae BSI, respectively, were included. Prior use of β-lactams (adjusted odds ratio [aOR] 3.9, 95% confidence intervals [CI]: 2.3-6.9), but not fluoroquinolones (aOR 1.0, 95% CI: 0.4-2.2), was a risk factor for PSA BSI. Immune compromised status (aOR 3.7, 95% CI: 2.0-6.7), respiratory source (aOR 4.4, 95% CI: 2.1-8.9), and prolonged hospitalization (aOR 1.9, 95% CI: 1.1-3.5), were predictors of PSA BSI. CONCLUSIONS Determination of class of previously used antibiotics among other clinical variables helps identify patients at risk of PSA BSI and offers opportunities to optimize empirical antimicrobial therapy.
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Affiliation(s)
- Katie Lynn Hammer
- Department of Clinical Pharmacy, Carolinas HealthCare System, Charlotte, NC, USA.
| | - Julie Ann Justo
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA; Department of Pharmacy, Palmetto Health Richland, Columbia, SC, USA
| | - P Brandon Bookstaver
- Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA; Department of Pharmacy, Palmetto Health Richland, Columbia, SC, USA
| | - Joseph Kohn
- Department of Pharmacy, Palmetto Health Richland, Columbia, SC, USA
| | - Helmut Albrecht
- Department of Medicine, Division of Infectious Diseases, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Majdi N Al-Hasan
- Department of Medicine, Division of Infectious Diseases, University of South Carolina School of Medicine, Columbia, SC, USA
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Furtado GH, Cardinal L, Macedo RS, Silva JO, Medeiros EA, Kuti JL, Nicolau DP. Pharmacokinetic/pharmacodynamic target attainment of intravenous β-lactam regimens against Gram-negative bacteria isolated in a Brazilian teaching hospital. Rev Soc Bras Med Trop 2015; 48:539-45. [DOI: 10.1590/0037-8682-0122-2015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 07/28/2015] [Indexed: 11/22/2022] Open
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Zhang JF, Zhu HY, Sun YW, Liu W, Huo YM, Liu DJ, Li J, Hua R. Pseudomonas aeruginosa Infection after Pancreatoduodenectomy: Risk Factors and Clinic Impacts. Surg Infect (Larchmt) 2015; 16:769-74. [PMID: 26237502 DOI: 10.1089/sur.2015.041] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of nosocomial infections, which is difficult to treat because of limited susceptibility to antimicrobial agents. In China, isolation rates of P. aeruginosa were observed to increase by year. The incidence of infectious complications after pancreatoduodenectomy (PD) were high. However, there was no data available regarding P. aeruginosa infection in patients undergoing PD. This study evaluated the risk factors and clinical impacts of P. aeruginosa infection on patient after PD. METHODS 119 patients who underwent PD with post-operative infectious complications were monitored for P. aeruginosa infection. The patients were grouped as P. aeruginosa infection and non-P. aeruginosa infection. Univariable and multivariable analyses were used to identify risk factors for P. aeruginosa infection. RESULTS 42 (35.3%) of the119 patients were P. aeruginosa positive after PD. The sites of P. aeruginosa infection included (1) abdominal drain fluid (76%); (2) sputum (7%); (3) central line catheter tip cultures (2%); and (4) combination of sites (14%). Pseudomonas aeruginosa isolates were susceptible to Polymyxin B, Amikacin and Gentamicin, resistant to Aztreonam Piperacillin-tazobactam, Imipenem and Ceftazidime. History of diabetes mellitus (OR=2.981, P=0.023), pancreatic fistula (OR=4.699, P=0.001), use of carbapenems (OR=3.236, P=0.013), and fluoroquinolones (OR=2.940, P=0.044), antibiotics, and length of ICU stay (OR=2.133, P=0.022) independently predicted post-operative P. aeruginosa infection. Pseudomonas aeruginosa infection was related to severe post-operative complications, including delayed gastric emptying and post-pancreatectomy hemorrhage, but was not related to not 30-d mortality or a longer post-operative stay. CONCLUSIONS This analytic study highlights the prevalence and high drug resistance of P. aeruginosa after PD. Pseudomonas aeruginosa infection was related to severe post-operative complications but not 30-d mortality. Measures to combat P. aeruginosa infection would likely decrease the accidence of P. aeruginosa infection and benefit patients' outcomes.
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Affiliation(s)
- Jun-Feng Zhang
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - Hong-Yan Zhu
- 2 Department of General Surgery, The First People's Hospital of Suqian, Suqian City , Jiangsu Province, China
| | - Yong-Wei Sun
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - Wei Liu
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - Yan-Miao Huo
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - De-Jun Liu
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - Jiao Li
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
| | - Rong Hua
- 1 Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, China
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Antibiotic Resistance Prevalence in Routine Bloodstream Isolates from Children's Hospitals Varies Substantially from Adult Surveillance Data in Europe. Pediatr Infect Dis J 2015; 34:734-41. [PMID: 25607829 DOI: 10.1097/inf.0000000000000652] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Surveillance of antimicrobial resistance (AMR) is central for defining appropriate strategies to deal with changing AMR levels. It is unclear whether childhood AMR patterns differ from those detected in isolates from adult patients. METHODS Resistance percentages of nonduplicate Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa bloodstream isolates from children less than 18 years of age reported to the Antibiotic Resistance and Prescribing in European Children (ARPEC) project were compared with all-age resistance percentages reported by the European Antimicrobial Resistance Surveillance Network (EARS-Net) for the same pathogen-antibiotic class combinations, period and countries. In addition, resistance percentages were compared between ARPEC isolates from children less than 1 year of age and children greater than or equal to1 year of age. RESULTS Resistance percentages for many important pathogen-antibiotic class combinations were different for ARPEC isolates compared with EARS-Net. E. coli and K. pneumoniae fluoroquinolone resistance percentages were substantially lower in ARPEC (13.4% and 17.9%) than in EARS-Net (23.0% and 30.7%), whereas the reverse was true for all pathogen-antibiotic class combinations in P. aeruginosa (for example, 27.3% aminoglycoside resistance in ARPEC, 19.3% in EARS-Net, 32.8% carbapenem resistance in ARPEC and 20.5% in EARS-Net), and for S. pneumoniae and macrolide resistance. For many Gram-negative pathogen-antibiotic class combinations, isolates from children greater than or equal to 1 year of age showed higher resistance percentages than isolates from children less than 1 year of age. CONCLUSIONS Age-stratified presentation of resistance percentage estimates by surveillance programs will allow identification of important variations in resistance patterns between different patient groups for targeted intervention.
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Migiyama Y, Yanagihara K, Kaku N, Harada Y, Yamada K, Nagaoka K, Morinaga Y, Akamatsu N, Matsuda J, Izumikawa K, Kohrogi H, Kohno S. Pseudomonas aeruginosa Bacteremia among Immunocompetent and Immunocompromised Patients: Relation to Initial Antibiotic Therapy and Survival. Jpn J Infect Dis 2015; 69:91-6. [PMID: 26073727 DOI: 10.7883/yoken.jjid.2014.573] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P < 0.01; 30-day mortality, 23% vs. 39%, P = 0.053). Multivariate analysis showed that a higher sequential organ failure assessment score (hazard ratio [HR]: 1.27, P < 0.01) and underlying malignancies (HR: 3.33, P < 0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, P < 0.01) and patients' immune status (HR: 0.29, P = 0.02) also had a significant impact on survival. However, there was a significant interaction between these 2 variables (P = 0.03 for interaction). A subgroup analysis showed that in immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).
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Affiliation(s)
- Yohei Migiyama
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences
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Population-based epidemiology and microbiology of community-onset bloodstream infections. Clin Microbiol Rev 2015; 27:647-64. [PMID: 25278570 DOI: 10.1128/cmr.00002-14] [Citation(s) in RCA: 201] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide. While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity. Community-onset BSIs are those that occur in outpatients or are first identified <48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases. The most common causes of community-onset BSI include Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrobial-resistant organisms, including methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase/metallo-β-lactamase/carbapenemase-producing Enterobacteriaceae, have emerged as important etiologies of community-onset BSI.
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Smith ZR, Tajchman SK, Dee BM, Bruno JJ, Qiao W, Tverdek FP. Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in an oncology population. J Oncol Pharm Pract 2015; 22:409-15. [DOI: 10.1177/1078155215586081] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Purpose Development of a combination antibiogram to identify combinations of antibiotics that have the highest likelihood of attaining one active agent in the empiric management of presumed Pseudomonas aeruginosa bacteremia. Methods Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31, 2012 were included in this analysis. The primary outcome was identification of effective combinations of beta-lactam and non-betalactam agents. An effective combination was defined as one which achieved in-vitro activity to greater than or equal to 85% of isolates collected. Furthermore, the addition of the non-beta-lactam agent was required to increase the in-vitro activity by at least 5% over beta-lactam monotherapy. Multiple secondary outcomes were evaluated. Results One hundred and twenty-three P. aeruginosa isolates were included from 99 patients. Single agent beta-lactam sensitivities ranged from 72.4 to 79.7%. Combination regimen sensitivities ranged from 73.5 to 96.7%. All combination regimens that included a beta-lactam plus an aminoglycoside were found to be effective per the study definition. Independent risk factors for MDR P. aeruginosa were receipt of intravenous (IV) antibiotics within 90 days and hospital length of stay (LOS) greater than or equal to five days. Increasing the number of antibiotics received was associated with a decrease in survival to hospital discharge. Conclusions Effective combination regimens included all beta-lactam aminoglycoside regimens. Receipt of IV antibiotics within 90 days and hospital LOS greater than or equal to five days were independent risk factors for MDR isolates.
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Affiliation(s)
- Zachary R Smith
- Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI, USA
| | - Sharla K Tajchman
- Division of Pharmacy, Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian M Dee
- Division of Pharmacy, Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey J Bruno
- Division of Pharmacy, Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wei Qiao
- Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Frank P Tverdek
- Division of Pharmacy, Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Werth BJ, Carreno JJ, Reveles KR. Shifting trends in the incidence of Pseudomonas aeruginosa septicemia in hospitalized adults in the United States from 1996-2010. Am J Infect Control 2015; 43:465-8. [PMID: 25783865 DOI: 10.1016/j.ajic.2015.01.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 01/22/2015] [Accepted: 01/26/2015] [Indexed: 11/24/2022]
Abstract
BACKGROUND Pseudomonas aeruginosa septicemia (PAS) is associated with high mortality rates and substantial resource utilization; however, the burden of PAS in the United States in recent years is unknown. METHODS This was a retrospective analysis of the U.S. National Hospital Discharge Surveys from 1996-2010. Adult patients with an ICD-9-CM code for PAS (038.43) were included. Incidence, in-hospital mortality, and hospital length of stay (LOS) for PAS discharges were reported. Incidence was calculated as PAS discharges per 10,000 total adult discharges. RESULTS Overall, 213,553 patients had a PAS discharge diagnosis during the study period. Patients had a median (interquartile range [IQR]) age of 69 (55-78) years and were predominately men (61%) and white (75%). PAS incidence declined from 6.5 per 10,000 in 1996 to 3.1 per 10,000 in 2001 and then increased to 6.5 per 10,000 in 2010. PAS incidence was highest in the Northeast (7.6 per 10,000) and lowest in the South (6.2 per 10,000). The overall mortality rate was 16%, but this ranged from 10%-26% over the study period. Median LOS was 10 (IQR, 6-19) days, and this varied over the study period (8-13 days). CONCLUSIONS The incidence of PAS has increased among hospitalized adults in the United States since 2001, with little evidence of improvement in mortality or LOS.
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Grimwood K, Kyd JM, Owen SJ, Massa HM, Cripps AW. Vaccination against respiratory Pseudomonas aeruginosa infection. Hum Vaccin Immunother 2014; 11:14-20. [PMID: 25483510 PMCID: PMC4514401 DOI: 10.4161/hv.34296] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Respiratory infections caused by Pseudomonas aeruginosa are a major clinical problem globally, particularly for patients with chronic pulmonary disorders, such as those with cystic fibrosis (CF), non-CF bronchiectasis (nCFB) and severe chronic obstructive pulmonary disease (COPD). In addition, critically ill and immunocompromised patients are also at significant risk of P. aeruginosa infection. For almost half a century, research efforts have focused toward development of a vaccine against infections caused by P. aeruginosa, but a licensed vaccine is not yet available. Significant advances in identifying potential vaccine antigens have been made. Immunisations via both the mucosal and systemic routes have been trialled in animal models and their effectiveness in clearing acute infections demonstrated. The challenge for translation of this research to human applications remains, since P. aeruginosa infections in the human respiratory tract can present both as an acute or chronic infection. In addition, immunisation prior to infection may not be possible for many patients with CF, nCFB or COPD. Therefore, development of a therapeutic vaccine provides an alternative approach for treatment of chronic infection. Preliminary animal and human studies suggest that mucosal immunisation may be effective as a therapeutic vaccine against P. aeruginosa respiratory infections. Nevertheless, more research is needed to improve our understanding of the basic biology of P. aeruginosa and the mechanisms needed to upregulate the induction of host immune pathways to prevent infection. Recognition of variability in the host immune responses for a range of patient health conditions at risk from P. aeruginosa infection is also required to support development of a successful vaccine delivery strategy and vaccine. Activation of mucosal immune responses may provide improved efficacy of vaccination for P. aeruginosa during both acute exacerbations and chronic infection.
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Affiliation(s)
- Keith Grimwood
- a School of Medicine; Griffith University; Gold Coast, Queensland Australia
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Characteristics, risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections. Infection 2014; 42:721-8. [DOI: 10.1007/s15010-014-0635-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 05/10/2014] [Indexed: 02/05/2023]
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Inghammar M, Engström G, Ljungberg B, Löfdahl CG, Roth A, Egesten A. Increased incidence of invasive bacterial disease in chronic obstructive pulmonary disease compared to the general population--a population based cohort study. BMC Infect Dis 2014; 14:163. [PMID: 24661335 PMCID: PMC3976148 DOI: 10.1186/1471-2334-14-163] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2013] [Accepted: 03/18/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Innate defence mechanisms of the airways are impaired in chronic obstructive pulmonary disease (COPD), predisposing patients to lower respiratory tract infections, but less is known about the association with other infections. In this population-based cohort study, we investigated the associations between COPD and invasive bacterial disease by comparing incidence rates of bacteraemia in COPD patients and randomly selected reference individuals from the general population. METHODS In this population based cohort study all patients with COPD, ≥40 years of age, who were discharged from hospitals in southern Sweden between 1990 and 2003 were identified in the Swedish Inpatient Register (n = 15,403). Age and gender matched reference individuals were randomly selected from the general population. Records were cross-referenced to the microbiological databases covering the region, 1990-2010. The hazard ratios (HR) of bloodstream infections and hospitalisations for infections were estimated by Cox proportional hazards regression. RESULTS We found that individuals with COPD had a 2.5-fold increased incidence of bacteraemia compared to the reference individuals from the general population adjusted for other co-morbidity and socio-economic status (hazard ratio: 2.5, 95% confidence interval: 2.2-2.7). The increased incidence of bacteraemia was paralleled by an increased incidence of hospitalisation for non-respiratory infections, i.e., skin infections, pyelonephritis, or septic arthritis. Despite higher absolute rates of bloodstream infections among COPD patients than among the general population, the distribution of different pathogens was similar. CONCLUSIONS In summary this population-based study shows COPD is associated with an increased incidence of invasive bacterial infections compared to the general population, indicating a general frailty of acquiring severe infections in addition to the specific susceptibility to infections of respiratory origin. The underlying contributory factors (e.g. smoking, corticosteroid use, co-morbid diseases or a frailty inherent to COPD itself) need to be disentangled in further studies.
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Affiliation(s)
- Malin Inghammar
- Infection Medicine, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
- Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
- Department of Infectious Diseases, Skåne University Hospital, SE-221 85 Lund, Sweden
| | - Gunnar Engström
- Cardiovascular Epidemiology Research Group, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Bengt Ljungberg
- Infection Medicine, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
| | - Claes-Göran Löfdahl
- Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
| | - Adam Roth
- Medical Microbiology, Department of Laboratory Sciences Malmö, Lund University, Skåne University Hospital Malmö, Malmö, Sweden
| | - Arne Egesten
- Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden
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Priebe GP, Goldberg JB. Vaccines for Pseudomonas aeruginosa: a long and winding road. Expert Rev Vaccines 2014; 13:507-19. [PMID: 24575895 DOI: 10.1586/14760584.2014.890053] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Despite the recognition of Pseudomonas aeruginosa as an opportunistic pathogen, no vaccine against this bacteria has come to market. This review describes the current state-of-the-art in vaccinology for this bacterium. This includes a discussion of those at risk for infection, the types of vaccines and the approaches for empirical and targeted antigen selection under development, as well as a perspective on where the field should go. In addition, the challenges in developing a vaccine for those individuals at risk are discussed.
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