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Khoury DM, Ghaoui N, El Tayar E, Dagher R, El Hawa M, Rubeiz N, Abbas O, Kurban M. Topical statins as antifungals: a review. Int J Dermatol 2024; 63:747-753. [PMID: 38344878 DOI: 10.1111/ijd.17068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 12/29/2023] [Accepted: 01/18/2024] [Indexed: 05/25/2024]
Abstract
Cutaneous fungal infections affect millions around the world. However, severe, multi-resistant fungal infections are increasingly being reported over the past years. As a result of the high rate of resistance which urged for drug repurposing, statins were studied and found to have multiple pleiotropic effects, especially when combined with other already-existing drugs. An example of this is the synergism found between several typical antifungals and statins, such as antifungals Imidazole and Triazole with a wide range of statins shown in this review. The main mechanisms in which they exert an antifungal effect are ergosterol inhibition, protein prenylation, mitochondrial disruption, and morphogenesis/mating inhibition. This article discusses multiple in vitro studies that have proven the antifungal effect of systemic statins against many fungal species, whether used alone or in combination with other typical antifungals. However, as a result of the high rate of drug-drug interactions and the well-known side effects of systemic statins, topical statins have become of increasing interest. Furthermore, patients with dyslipidemia treated with systemic statins who have a new topical fungal infection could benefit from the antifungal effect of their statin. However, it is still not indicated to initiate systemic statins in patients with topical mycotic infections if they do not have another indication for statin use, which raises the interest in using topical statins for fungal infections. This article also tackles the different formulations that have been studied to enhance topical statins' efficacy, as well as the effect of different topical statins on distinct dermatologic fungal diseases.
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Affiliation(s)
- Dana M Khoury
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Nohra Ghaoui
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
| | | | - Ruby Dagher
- American University of Beirut, Beirut, Lebanon
| | - Mariana El Hawa
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Nelly Rubeiz
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ossama Abbas
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mazen Kurban
- Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
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Fernández-Ruiz M, Sánchez Moreno B, Santiago Almeda J, Rodríguez-Goncer I, Ruiz-Merlo T, Redondo N, López-Medrano F, San Juan R, Andrés A, Aguado JM. Previous use of statins does not improve the outcome of bloodstream infection after kidney transplantation. Transpl Infect Dis 2023; 25:e14132. [PMID: 37605530 DOI: 10.1111/tid.14132] [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: 06/23/2023] [Revised: 08/02/2023] [Accepted: 08/10/2023] [Indexed: 08/23/2023]
Abstract
Previous studies have suggested that exposure to statins confers a protective effect in bloodstream infection (BSI) due to the anti-inflammatory and immunomodulatory properties attributed to these lipid-lowering drugs. Scarce evidence is available for the solid organ transplant population. Therefore, we compared the time to clinical cure (primary outcome) and the time to fever resolution, new requirement of intensive care unit admission or renal replacement therapy, and 30-day all-cause mortality (secondary outcomes) between kidney transplant (KT) recipients with post-transplant BSI that were receiving or not statin therapy for at least the previous 30 days. We included 80 KT recipients that developed 109 BSI episodes (43 [39.4%] and 66 [60.6%] episodes within the statin and non-statin groups, respectively). The median interval since the initial prescription to BSI was 512 days (interquartile range [IQR]: 172-1388). Most episodes were of urinary source and due to Enterobacterales. There were no differences in the median time to clinical cure in the statin and non-statin groups (3.4 [IQR: 3-6.8] versus 4 [IQR: 2-6] days; p-value = .112). The lack of effect was confirmed by multiple linear regression analysis adjusted for confounding factors (standardized β coefficient = 0.040; p-value = .709). No significant differences were observed for any of the secondary outcomes either. Vital signs and laboratory values at BSI onset and after 72-96 h were similar in both groups. In conclusion, previous statin therapy had no apparent protective effect on the outcome of post-transplant BSI among KT recipients.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Beatriz Sánchez Moreno
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Javier Santiago Almeda
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Isabel Rodríguez-Goncer
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Natalia Redondo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Amado Andrés
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
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Villalobos APC, Foroutan F, Davoudi S, Kothari S, Martinu T, Singer LG, Keshavjee S, Husain S. Statin Use May Be Associated With a Lower Risk of Invasive Aspergillosis in Lung Transplant Recipients. Clin Infect Dis 2023; 76:e1379-e1384. [PMID: 35900334 DOI: 10.1093/cid/ciac551] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 06/23/2022] [Accepted: 06/30/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Statins are competitive inhibitors of 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase) that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented. METHODS This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of 2 weeks duration prior to IA), adjusting for other known IA risk factors. RESULTS We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). In total, 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (interquartile range [IQR]: 305 to 346). And 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (P = .002, SHR 0.30, 95% confidence interval [CI] 95% .14-.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs 123 (27%) in the statin group (P = .038). CONCLUSIONS The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.
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Affiliation(s)
- Armelle Pérez-Cortés Villalobos
- Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.,Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Farid Foroutan
- Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Setareh Davoudi
- Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Sagar Kothari
- Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Tereza Martinu
- Lung Transplant Program, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Lianne G Singer
- Lung Transplant Program, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Shaf Keshavjee
- Lung Transplant Program, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Shahid Husain
- Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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Xu Q, Zheng B, Shen P, Xiao Y. Protective efficacy of statins in patients with Klebsiella pneumoniae bloodstream infection. Front Cell Infect Microbiol 2023; 12:1087701. [PMID: 36683706 PMCID: PMC9849249 DOI: 10.3389/fcimb.2022.1087701] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Patients with bloodstream infection of Klebsiella pneumoniae (BSI-KP) have a high risk of death and septic shock. This study aims to identify the risk factors for mortality and severity in patients of BSI-KP. METHODS Data of BSI-KP patients were extracted from the MIMIC IV (Medical Information Mart for Intensive Care IV) database, and patients infected with only K. pneumoniae in blood were included in this study. The risk factors of 28-day mortality and septic shock in BSI-KP patients were analyzed, respectively. RESULTS A total of 279 patients enrolled and the all-cause 28-day mortality rate was 11.8%. The use of statins (OR 0.220, 95% CI 0.060-0.801, p = 0.022) and quinolones (OR 0.356, 95% CI 0.143-0.887, p = 0.027) were both independent protective factors for death within 28 days, while the use of vasoactive drugs (OR 7.377, 95% CI 1.775-30.651, p = 0.006) was a risk factor. Besides, pulmonary disease (OR 2.348, 95% CI 1.126-4.897, p = 0.023), bleeding and coagulation disorders (OR 3.626, 95% CI 1.783-7.372, p < 0.001), respiratory failure (OR 2.823, 95% CI 0.178-6.767, p = 0.020) and kidney dysfunction (OR 2.450, 95% CI 1.189-5.047, p = 0.015) were independent risk factors for patients suffered from septic shock while hypertension was a protective one. The receiver operating characteristic (ROC) curves could well predict the risk of death within 28-day (area under ROC = 0.855, 95% CI = 0.796-0.914, p < 0.001) and septic shock (AUROC = 0.815, 95% CI = 0.755-0.874, p < 0.001) in patients with BSI-KP. CONCLUSION The use of statins could decrease the risk of 28-day mortality in patients of BSI-KP. The risk factor-based prediction model provided evidence for drug treatment in BSI-KP patients. Paying more attention to the strategy of drug treatment will be an optimal way to improve patient's outcome in clinical practice.
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Affiliation(s)
- Qian Xu
- Laboratory Medicine Center, Department of Transfusion Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, China
| | - Beiwen Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, China
| | - Ping Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong Province, China
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, China
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Gelosa P, Castiglioni L, Camera M, Sironi L. Repurposing of drugs approved for cardiovascular diseases: Opportunity or mirage? Biochem Pharmacol 2020; 177:113895. [PMID: 32145263 DOI: 10.1016/j.bcp.2020.113895] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Accepted: 02/27/2020] [Indexed: 02/08/2023]
Abstract
Drug repurposing is a promising way in drug discovery to identify new therapeutic uses -different from the original medical indication- for existing drugs. It has many advantages over traditional approaches to de novo drug discovery, since it can significantly reduce healthcare costs and development timeline. In this review, we discuss the possible repurposing of drugs approved for cardiovascular diseases, such as β-blockers, angiotensin converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs), statins, aspirin, cardiac glycosides and low-molecular-weight heparins (LMWHs). Indeed, numerous experimental and epidemiological studies have reported promising anti-cancer activities for these drugs. It is worth mentioning, however, that the results of these studies are often controversial and very few data were obtained by controlled prospective clinical trials. Therefore, no final conclusion has yet been reached in this area and no final recommendations can be made. Moreover, β-blockers, ARBs and statins showed promising results in randomised controlled trials (RCTs) where pathological conditions other than cancer were considered. The results obtained have led or may lead to new indications for these drugs. For each drug or class of drugs, the potential molecular mechanisms of action justifying repurposing, results obtained in vitro and in animal models and data from epidemiological and randomized studies are described.
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Affiliation(s)
- Paolo Gelosa
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Laura Castiglioni
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy
| | - Marina Camera
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy.
| | - Luigi Sironi
- Department of Pharmaceutical Sciences, University of Milan, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy
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Abstract
Fungal infections are estimated to be responsible for 1.5 million deaths annually. Global anti-microbial resistance is also observed for fungal pathogens, and scientists are looking for new antifungal agents to address this challenge. One potential strategy is to evaluate currently available drugs for their possible antifungal activity. One of the suggested drug classes are statins, which are commonly used to decrease plasma cholesterol and reduce cardiovascular risk associated with low density lipoprotein cholesterol (LDL-c). Statins are postulated to possess pleiotropic effects beyond cholesterol lowering; improving endothelial function, modulating inflammation, and potentially exerting anti-microbial effects. In this study, we reviewed in-vitro and in-vivo studies, as well as clinical reports pertaining to the antifungal efficacy of statins. In addition, we have addressed various modulators of statin anti-fungal activity and the potential mechanisms responsible for their anti-fungal effects. In general, statins do possess anti-fungal activity, targeting a broad spectrum of fungal organisms including human opportunistic pathogens such as Candida spp. and Zygomycetes, Dermatophytes, alimentary toxigenic species such as Aspergillus spp., and fungi found in device implants such as Saccharomyces cerevisiae. Statins have been shown to augment a number of antifungal drug classes, for example, the azoles and polyenes. Synthetic statins are generally considered more potent than the first generation of fungal metabolites. Fluvastatin is considered the most effective statin with the broadest and most potent fungal inhibitory activity, including fungicidal and/or fungistatic properties. This has been demonstrated with plasma concentrations that can easily be achieved in a clinical setting. Additionally, statins can potentiate the efficacy of available antifungal drugs in a synergistic fashion. Although only a limited number of animal and human studies have been reported to date, observational cohort studies have confirmed that patients using statins have a reduced risk of candidemia-related complications. Further studies are warranted to confirm our findings and expand current knowledge of the anti-fungal effects of statins.
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Affiliation(s)
- Alexis Guenette
- Division of Infectious Disease, University Health Network, University of Toronto, 585 University Avenue, 11 PMB 138, Toronto, Ontario M5G 2N2, Canada
| | - Shahid Husain
- Division of Infectious Disease, Multi-Organ Transplant Program, University Health Network, University of Toronto, 585 University Avenue, 11 PMB 138, Toronto, Ontario M5G 2N2, Canada.
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He Q, Liu P, Li X, Su K, Peng D, Zhang Z, Xu W, Qin Z, Chen S, Li Y, Qiu J. Risk factors of bloodstream infections in recipients after liver transplantation: a meta-analysis. Infection 2018; 47:77-85. [PMID: 30370489 DOI: 10.1007/s15010-018-1230-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 09/28/2018] [Indexed: 12/13/2022]
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Pawar AM, LaPlante KL, Timbrook TT, Caffrey AR. Improved survival with continuation of statins in bacteremic patients. SAGE Open Med 2018; 6:2050312118801707. [PMID: 30364748 PMCID: PMC6198392 DOI: 10.1177/2050312118801707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 08/27/2018] [Indexed: 01/26/2023] Open
Abstract
Objectives: Varying statin exposures in bacteremic patients have different impacts on mortality. Among patients with adherent statin use, we sought to evaluate the impact of statin continuation on inpatient mortality in bacteremic patients. Methods: A retrospective cohort study was conducted using Optum ClinformaticsTM with matched Premier Hospital data (October 2009–March 2013). Patients with a primary diagnosis of bacteremia and 6 months of continuous enrollment prior to the admission, receiving antibiotics at least 2 days of antibiotics during the first 3 days of admission, were selected for inclusion. Furthermore, patients demonstrating adherent statin use based on 90 days of continuous therapy prior to admission were included. We then compared those continuing statin therapy for at least the first 5 days after admission and those not continuing during the admission. Results: Simvastatin (53.2%) and atorvastatin (33.8%) were the most commonly used statins among the 633 patients who met our inclusion and exclusion criteria. Propensity score adjusted Cox proportional hazards regression models demonstrated significantly lower inpatient mortality among those continuing statin therapy compared with those not continuing (n = 232 vs 401, adjusted hazard ratio 0.25, 95% confidence interval 0.08–0.79). Conclusion: Among patients adherent to their statin therapy prior to a bacteremia hospitalization, continued statin use after admission increased survival by 75% compared with those not continuing.
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Affiliation(s)
- Ajinkya M Pawar
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA
| | - Kerry L LaPlante
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA.,Infectious Diseases Research Program, Veterans Affairs Medical Center, Providence, RI, USA
| | - Tristan T Timbrook
- Infectious Diseases Research Program, Veterans Affairs Medical Center, Providence, RI, USA
| | - Aisling R Caffrey
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA.,Infectious Diseases Research Program, Veterans Affairs Medical Center, Providence, RI, USA.,School of Public Health, Brown University, Providence, RI, USA
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Lorente L. New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma. World J Gastroenterol 2018; 24:4230-4242. [PMID: 30310256 PMCID: PMC6175764 DOI: 10.3748/wjg.v24.i37.4230] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 08/18/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
The outcome prediction of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) was classically established using various macromorphological factors and serum alpha-fetoprotein levels prior to LT. However, other biomarkers have recently been reported to be associated with the prognosis of HCC patients undergoing to LT. This review summarizes clinical data on these new biomarkers. High blood levels of malondialdehyde, total antioxidant capacity, caspase-cleaved cytokeratin-18, soluble CD40 ligand, substance P, C-reactive protein, and vascular endothelial growth factor, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood, high peripheral blood expression of human telomerase reverse transcriptase messenger ribonucleic acid, and high HCC expression of dickkopf-1 have recently been associated with decreased survival rates. In addition, high blood levels of des-gamma-carboxy prothrombin, and high HCC expression of glypican-3, E-cadherin and beta-catenin have been associated with increased HCC recurrence. Additional research is necessary to establish the prognostic role of these biomarkers in HCC prior to LT. Furthermore, some of these biomarkers are also interesting because their potential modulation could help to create new research lines for improving the outcomes of those patients.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, Santa Cruz de Tenerife 38320, Spain
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11
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Pawar AM, LaPlante KL, Timbrook TT, Caffrey AR. Optimal duration for continuation of statin therapy in bacteremic patients. Ther Adv Infect Dis 2018; 5:83-90. [PMID: 30224951 DOI: 10.1177/2049936118775926] [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: 01/29/2018] [Accepted: 04/19/2018] [Indexed: 11/15/2022] Open
Abstract
Background Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure. Objectives To quantify statin therapy duration associated with decreased mortality in bacteremic statin users. Methods We conducted a case-control study using OptumClinformatics™ with matched Premier hospital data (1 October 2009-31 March 2013). Cases who died during the hospitalization were matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin therapy duration was evaluated in patients with at least 90 days of pre-admission continuous statin use. Classification and regression tree (CART) analysis was conducted to identify the optimal duration of statin continuation which provided the lowest inpatient mortality. Logistic regression was used to calculate the odds of mortality. Results We included 58 DRS matched pairs of cases and controls: 47 patients (41%) continued statin therapy during the hospital admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned the continuation of statin therapy at ⩾2 days, representing lower mortality for patients who continued statins for 2 days or more and higher mortality for patients who did not continue or remained on statins for only 1 day. Inpatient mortality was 76% lower among those with at least 2 days of continued statin use (odds ratio 0.24, 95% confidence interval 0.11-0.55). Conclusion Among matched cases and controls with at least 90 days of baseline statin use prior to the admission, the continuation of statins for at least 2 days after admission demonstrated a survival benefit among bacteremic patients.
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Affiliation(s)
- Ajinkya M Pawar
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA
| | - Kerry L LaPlante
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA Veterans Affairs Medical Center, Providence, RI, USA
| | - Tristan T Timbrook
- Department of Pharmacy, University of Utah Health, Salt Lake City, Utah, USA
| | - Aisling R Caffrey
- Department of Pharmacy Practice, College of Pharmacy, The University of Rhode Island, Kingston, RI, USA Veterans Affairs Medical Center, Providence, RI, USA Brown University School of Public Health, Providence, RI, USA
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12
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High serum soluble CD40L levels previously to liver transplantation in patients with hepatocellular carcinoma are associated with mortality at one year. J Crit Care 2017; 43:316-320. [PMID: 29020665 DOI: 10.1016/j.jcrc.2017.09.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 08/29/2017] [Accepted: 09/15/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE CD40L and its soluble form (sCD40L) are proteins of the tumor necrosis factor superfamily (TNFSF) that exhibit prothrombotic and proinflammatory properties when binding to CD40, which is a cell surface receptor of the tumor necrosis factor receptor superfamily (TNFRSF). High circulating levels of sCD40L have been associated with poor prognosis in patients with hepatocellular carcinoma (HCC). However, it is unknown whether there is an association between circulating sCD40L levels and survival in patients with HCC underwent to liver transplantation (LT), and this was the objective of that study. METHODS Serum sCD40L levels were measured in a total of 139 patients before LT (124 survivors at 1year of LT and 15 non-survivors). The end-point study was 1year survival after liver LT. RESULTS We found that 1-year non-surviving patients showed higher serum sCD40L levels than survivor patients (p=0.02). We found in logistic regression analysis that serum sCD40L levels higher than 321pg/mL (Odds Ratio=6.86; 95% confidence interval=2.06-22.76; p=0.002) and age of LT deceased donor were associated with death at 1year. CONCLUSIONS The new finding of our study was that high serum sCD40L levels previously to LT in patients with HCC are associated with higher mortality at one year.
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Lorente L, Martín MM, Pérez-Cejas A, Ferreres J, Solé-Violán J, Labarta L, Díaz C, Jiménez A. Non-survivor septic patients have persistently higher serum sCD40L levels than survivors. J Crit Care 2017; 41:177-182. [PMID: 28570959 DOI: 10.1016/j.jcrc.2017.05.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 04/17/2017] [Accepted: 05/20/2017] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non-survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker?. This study was developed to answer these asks. METHODS Study from 6 Spanish Intensive Care Units with 291 severe septic patients. There were determined serum levels of sCD40L and tumor necrosis factor (TNF)-alpha during the first week. The end-point study was 30-day mortality. RESULTS We found that serum sCD40L at days 1, 4, and 8 could predict mortality at 30days, and are associated with mortality. CONCLUSIONS The novel findings of our study were that there were higher serum sCD40L levels persistently during the first week in non-survivor than in survivor patients, that there is an association between serum sCD40L levels during the first week and sepsis mortality, and that serum sCD40L levels during the first week could be used as sepsis mortality biomarker.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna 38320, Tenerife, Spain.
| | - María M Martín
- Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Crta Rosario s/n, Santa Cruz Tenerife 38010, Spain.
| | - Antonia Pérez-Cejas
- Laboratory Deparment, Hospital Universitario de Canarias, Ofra, s/n, La Laguna 38320, Tenerife, Spain.
| | - José Ferreres
- Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avda. Blasco Ibáñez no17-19, Valencia 46004, Spain.
| | - Jordi Solé-Violán
- Intensive Care Unit. Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, Las Palmas de Gran Canaria 35010, Spain.
| | - Lorenzo Labarta
- Intensive Care Unit, Hospital San Jorge de Huesca, Avenida Martínez de Velasco no36, Huesca 22004, Spain.
| | - César Díaz
- Intensive Care Unit, Hospital Insular, Plaza Dr. Pasteur s/n, Las Palmas de Gran Canaria 35016, Spain.
| | - Alejandro Jiménez
- Research Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna 38320, Tenerife, Spain.
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Qiao B, Wu J, Wan Q, Zhang S, Ye Q. Factors influencing mortality in abdominal solid organ transplant recipients with multidrug-resistant gram-negative bacteremia. BMC Infect Dis 2017; 17:171. [PMID: 28241746 PMCID: PMC5327527 DOI: 10.1186/s12879-017-2276-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 02/21/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although multidrug-resistant (MDR) gram-negative bacteremia (GNB) has been recognized as an important cause of morbidity and mortality among abdominal solid organ transplant (ASOT) recipients, there are no data on its prognostic factors after an interim standard definition of MDR was proposed in 2012. The objective of this study was to describe the epidemiology, microbiology, and predictors of infection-related 30-day mortality in ASOT recipients with MDR GNB. METHODS We performed a retrospective, double-center analysis of ASOT patients with MDR GNB over a 13-year study period. Univariate and multivariate analyses were performed to identify the risk factors for mortality. RESULTS During the observational period, 2169 subjects underwent ASOT. Ninety-nine episodes of MDR GNB were diagnosed in 91 (4.6%) ASOT recipients, with a predominance of E.coli (29 isolates, 29.3%) and A.baumanii (24 isolates, 24.2%). The median age of these 91 recipients was 45 years (interquartile range 35-54). Mortality after the first episode of MDR GNB was 39.6% (36 deaths). The univariate analysis identified the following variables as predictors of MDR GNB-related mortality: lung focus (P = 0.001),nosocomial origin (P = 0.002), graft from donation after cardiac death or deceased donors (P = 0.023), presence of other concomitant bloodstream infection (P < 0.001), temperature of 40 °C or greater at the onset of MDR GNB (P = 0.039), creatinine > 1.5 mg/dl (P = 0.006), albumin < 30 g/L (P = 0.009), platelet count < 50,000/mm3 (P < 0.001), and septic shock (P < 0.001). In the multivariate logistic regression analysis, septic shock (odds ratio (OR) = 160.463, 95% confidence interval (CI) = 19.377-1328.832, P < .001), as well as creatinine > 1.5 mg/dl (OR = 24.498, 95% CI = 3.449-173.998, P = 0.001), nosocomial origin (OR = 23.963, 95% CI = 1.285-46.991, P = 0.033), and presence of other concomitant bloodstream infections (OR = 27.074, 95% CI = 3.937-186.210, P = 0.001) were the variables associated with MDR GNB-related 30-day mortality. CONCLUSIONS MDR GNB was associated with high morbidity and mortality in ASOT recipients, with a predominant causative organisms being E.coli and A.baumanii. Nosocomial origin, as well as presence of other concomitant bloodstream infections, increased creatinine level and septic shock were the main predictors of MDR GNB-related 30-day mortality.
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Affiliation(s)
- Bingbing Qiao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People's Republic of China
| | - Jianzhen Wu
- Department of Cadre Care, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, People's Republic of China
| | - Qiquan Wan
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, People's Republic of China.
| | - Sheng Zhang
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, People's Republic of China
| | - Qifa Ye
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, People's Republic of China
- Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, People's Republic of China
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Evidence To Support Continuation of Statin Therapy in Patients with Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother 2017; 61:AAC.02228-16. [PMID: 28069650 DOI: 10.1128/aac.02228-16] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 12/22/2016] [Indexed: 12/21/2022] Open
Abstract
In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in Staphylococcus aureus bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive S. aureus blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii) de novo users initiating at culture. Nonusers included patients without statins in the year prior to culture through discharge. Propensity score-matched Cox proportional hazards regression models were developed. We were able to balance significantly different baseline characteristics using propensity score matching for pretreated without continuation (n = 331), pretreated with continuation (n = 141), and de novo (n = 177) statin users compared to nonusers. We observed a significantly lower 30-day mortality rate (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.25 to 0.84; number needed to treat [NNT], 10) among pretreated and continued statin users, while protective effects were not observed in de novo (HR, 1.04; 95% CI, 0.60 to 1.82; NNT, undefined) or pretreated but not continued (HR, 0.92; 95% CI, 0.64 to 1.32; NNT, 47) users. In our national cohort study among patients with S. aureus bacteremia, continuation of statin therapy among incident statin users was associated with significant beneficial effects on mortality, including a 54% lower 30-day mortality rate.
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Luo A, Zhong Z, Wan Q, Ye Q. The Distribution and Resistance of Pathogens Among Solid Organ Transplant Recipients with Pseudomonas aeruginosa Infections. Med Sci Monit 2016; 22:1124-1130. [PMID: 27045418 PMCID: PMC4824462 DOI: 10.12659/msm.896026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Accepted: 10/30/2015] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Pseudomonas aeruginosa infection remains a life-threatening complication after solid organ transplantation (SOT). We aimed to investigate the distribution and drug susceptibility of pathogens, and clinical characteristics of SOT recipients with Pseudomonas aeruginosa infections. MATERIAL/METHODS A total of 55 SOT recipients who developed 61 episodes of Pseudomonas aeruginosa infections between January 1, 2003 and July 31, 2015 were retrospectively analyzed. The distribution and the drug susceptibility of Pseudomonas aeruginosa were reviewed. RESULTS The most common site from which 61 Pseudomonas aeruginosa rods were isolated were the lungs (57.4%, n=37), followed by the blood (27.9%, n=17). There were 35, 18, and 9 recipients accompanied with a serum creatinine level of >1.5 mg/dL, lymphocyte count of <300/mm(3), and a serum albumin level of <30 g/L, respectively. Seven patients each presented with white blood cell count of >15,000/mm(3) and platelet count of <50,000/mm(3). There were 6 (10.9%) cases of septic shocks and 18 (32.7%) deaths. Antibiotic resistance rate of all Pseudomonas aeruginosa to 4 of 10 antibiotics investigated was more than 50%. Of these 61 Pseudomonas aeruginosa isolates, 47.5% were carbapenem-resistant. The rods were relatively sensitive to piperacillin-tazobactam, levofloxacin, amikacin, and cefoperazone-sulbactam (resistance rate <40%). CONCLUSIONS The clinical presentation of Pseudomonas aeruginosa infections included high body temperature, decreased platelet count, elevated white blood cell count, a high nosocomial origin and mortality, and onset in the late period after transplantation. According to our findings, piperacillin-tazobactam, levofloxacin, amikacin, and cefoperazone-sulbactam, alone or combination, are recommended to treat SOT recipients with Pseudomonas aeruginosa infections.
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Affiliation(s)
- Aijing Luo
- Key Laboratory of Medical Information Research (Central South University), College of Hunan Province, Changsha, Hunan, P.R. China
| | - Zhuqing Zhong
- Nursing Department, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - Qifa Ye
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
- Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, P.R. China
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Berenger BM, Doucette K, Smith SW. Epidemiology and risk factors for nosocomial bloodstream infections in solid organ transplants over a 10-year period. Transpl Infect Dis 2016; 18:183-90. [PMID: 26818427 DOI: 10.1111/tid.12505] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 10/09/2015] [Accepted: 12/03/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND Bloodstream infections (BSIs) are a leading cause of morbidity and mortality in solid organ transplantation (SOT). We sought to determine the types of nosocomial BSIs and risk factors for them in SOT. METHODS Prospectively collected databases of all SOT and nosocomial BSIs occurring at our institution for a 10-year period were reviewed. RESULTS From 2003-2012, we observed 157 nosocomial BSI episodes in 2257 SOTs, the majority of which were caused by staphylococci and enterococci (67.5%). The most common sources of BSI were central line, organ space, respiratory, and gastrointestinal. Kidney transplant patients had the lowest risk of acquiring a BSI compared with other SOT types. Lung transplant patients were at increased risk of methicillin-resistant Staphylococcus aureus BSI and heart transplant patients were at increased risk of a Candida albicans BSI, when compared to other organ transplant types. When coagulase-negative Staphylococcus (CoNS) or C. albicans was isolated, the central line was most often the source. The implementation of central-line bundles during the study period correlated temporally with a decreased rate of CoNS BSI. Over the 10-year period, vancomycin-resistant enterococci became the most common enterococcal BSI. Donor-positive cytomegalovirus status was associated with an increased risk of BSI, when compared to donor-negative patients. CONCLUSIONS This study demonstrates the common sources, risk factors, and causative organisms of BSI, which can guide empiric antibiotic choices, and highlights areas where preventative interventions could be targeted to prevent nosocomial BSI in SOT.
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Affiliation(s)
- B M Berenger
- Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.,Alberta Provincial Laboratory for Public Health, Edmonton, Alberta, Canada
| | - K Doucette
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - S W Smith
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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Abstract
Solid-organ transplantation (SOT) has become the preferred strategy to treat a number of end-stage organ disease, because a continuous improvement in survival and quality of life. While preventive strategies has decreased the risk for classical opportunistic infections (such as viral, fungal and parasite infections), bacterial infections, and particularly bloodstream infections (BSIs) remain the most common and life-threatening complications in SOT recipients. The source of BSI after transplant depends on the type of transplantation, being urinary tract infection, pneumonia, and intraabdominal infections the most common infections occurring after kidney, lung and liver transplantation, respectively. The risk for candidemia is higher in abdominal-organ than in thoracic-organ transplantation. Currently, the increasing prevalence of multi-drug resistant (MDR) Gram-negative pathogens, such as extended-spectrum betalactamase-producing Enterobacteriaciae and carbapenem-resistant Klebsiella pneumoniae, is causing particular concerns in SOT recipients, a population which presents several risk factors for developing infections due to MDR organisms. The application of strict preventive policies to reduce the incidence of post transplant BSIs and to control the spread of MDR organisms, including the implementation of specific stewardship programs to avoid the overuse of antibiotics and antifungal drugs, are essential steps to reduce the impact of post transplant infections on allograft and patient outcomes.
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Affiliation(s)
- Antonios Kritikos
- a Infectious Diseases Service, University Hospital and University of Lausanne , Lausanne , Switzerland
| | - Oriol Manuel
- a Infectious Diseases Service, University Hospital and University of Lausanne , Lausanne , Switzerland.,b Transplantation Center, University Hospital and University of Lausanne , Lausanne , Switzerland
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19
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Wan Q, Ye Q, Huang F. The Bacteremia Caused by Non-Lactose Fermenting Gram-Negative Bacilli in Solid Organ Transplant Recipients. Surg Infect (Larchmt) 2015; 16:479-489. [PMID: 26181230 DOI: 10.1089/sur.2015.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Blood stream infections (BSIs) remain as a serious life-threatening condition after solid organ transplant (SOT). In recent years, a progressive growth in the incidence of bacteremia caused by non-lactose fermenting gram-negative bacilli (NLF GNB) has been observed. NLF GNB led to high mortality among SOT recipients with bacteremia and were difficult to treat because of their high drug resistance to commonly used antibiotics. METHODS Two electronic databases, PUBMED and EMBASE, were searched for relevant literature published up to January 2015, to better understand the characteristics of bacteremia because of NLF GNB. RESULTS The morbidity and mortality rates of bacteremia because of NLF GNB depend on the types of organisms and transplantation. Multi-drug resistant NLF GNB ranged from 9.8% to 12.5% of all NLF GNB causing BSIs among SOT recipients. Certain factors can predispose SOT recipients to NLF GNB bacteremia, which included previous transplantation, hospital-acquired BSIs, and prior intensive care unit admission. Combination therapy may be beneficial in the treatment of NLF GNB bacteremia to enhance antimicrobial activity, provide synergistic interactions, relieve side effects, and minimize superinfections. CONCLUSIONS Prevention is pivotal in minimizing the morbidity and mortality associated with NLF GNB bacteremia after SOT. To improve the outcomes of SOT recipients with NLF GNB bacteremia, prevention is pivotal, and combination therapy of antibiotics may be beneficial.
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Affiliation(s)
- Qiquan Wan
- 1 Department of Transplant Surgery, The Third Xiangya Hospital, Central South University , Changsha, Hunan, China
| | - Qifa Ye
- 1 Department of Transplant Surgery, The Third Xiangya Hospital, Central South University , Changsha, Hunan, China
- 2 Department of Transplant Surgery, Zhongnan Hospital, Wuhan University , Wuhan, China
| | - Feizhou Huang
- 3 Department of General Surgery, The Third Xiangya Hospital, Central South University , Changsha, China
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20
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Wan Q, Luo A, Ye Q, Liu S, Zhou J. Predictors of shock and mortality in solid organ transplant recipients with bacteremia caused by non-lactose-fermenting gram-negative bacilli. Infect Dis (Lond) 2015; 48:32-39. [PMID: 26329287 DOI: 10.3109/23744235.2015.1051106] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND More data on bacteremia due to non-lactose fermenting gram-negative bacilli (NLF GNB) in solid organ transplant (SOT) recipients are needed. We aimed to investigate the epidemiology, microbiology, and risk factors for mortality and septic shock due to NLF GNB bacteremia in SOT recipients. METHODS We performed a retrospective, double-center study over a 12-year study period. The risk factors for mortality and septic shock in SOT recipients with NLF GNB bacteremia were assessed with multivariate logistic regression analysis. RESULTS A total of 230 episodes of bloodstream infections (BSIs) occurred in 159 SOT recipients. Fifty episodes of NLF GNB bacteremia were detected in 47 SOT recipients, with a predominance of Acinetobacter baumanii (27 isolates, 54.0%). The antibiotic resistance rate of all NLF GNB to 10 of 12 antibiotics investigated was more than 50%. The independent risk factors associated with septic shock were platelet count < 50 000/mm(3) (odds ratio (OR) = 14.41, 95% confidence interval (CI) = 2.64-78.71, p = 0.002) and late-onset bacteremia (time of onset more than 2 months post-transplant) (OR = 10.87, 95% CI = 1.79-65.89, p = 0.009). Lung focus (OR = 32.91, 95% CI = 2.56-423.18, p = 0.007) and septic shock (OR = 70.38, 95% CI = 4.21-1176.21, p = 0.003) were risk factors for bacteremia-related mortality. CONCLUSIONS The drug resistance of the pathogens and the morbidity and mortality rates of NLF GNB bacteremia were high in SOT recipients. For septic shock, associated risk factors were thrombocytopenia and late-onset bacteremia. The risk factors significantly associated with mortality were lung focus and septic shock.
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Affiliation(s)
- Qiquan Wan
- a From the Department of Transplant Surgery , Third Xiangya Hospital, Central South University , Changsha, Hunan , China
| | - Aijing Luo
- b Key Laboratory of Medical Information Research (Central South University), College of Hunan Province , Changsha, Hunan , China
| | - Qifa Ye
- a From the Department of Transplant Surgery , Third Xiangya Hospital, Central South University , Changsha, Hunan , China
- c Department of Transplant Surgery , Zhongnan Hospital, Wuhan University , Wuhan, Hubei , China
| | - Shan Liu
- d Adelphi University College of Nursing and Public Health , Garden City , NY , USA
| | - Jiandang Zhou
- e Department of Clinical Laboratory of Microbiology , Third Xiangya Hospital, Central South University , Changsha, Hunan , China
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Wan QQ, Ye QF, Yuan H. Multidrug-resistant Gram-negative bacteria in solid organ transplant recipients with bacteremias. Eur J Clin Microbiol Infect Dis 2015; 34:431-437. [PMID: 25388855 DOI: 10.1007/s10096-014-2271-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 10/28/2014] [Indexed: 12/11/2022]
Abstract
Bloodstream infections (BSIs) remain as life-threatening complications and are associated with significant morbidity and mortality among solid organ transplant (SOT) recipients. Multidrug-resistant (MDR) Gram-negative bacteria can cause serious bacteremias in these recipients. Reviews have aimed to investigate MDR Gram-negative bacteremias; however, they were lacking in SOT recipients in the past. To better understand the characteristics of bacteremias due to MDR Gram-negative bacteria, optimize preventive and therapeutic strategies, and improve the outcomes of SOT recipients, this review summarize the epidemiology, clinical and laboratory characteristics, and explores the mechanisms, prevention, and treatment of MDR Gram-negative bacteria.
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Affiliation(s)
- Q Q Wan
- Department of Transplant Surgery, the Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China
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22
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Tralhão AF, Cés de Souza-Dantas V, Salluh JI, Póvoa PM. Impact of statins in outcomes of septic patients: a systematic review. Postgrad Med 2015; 126:45-58. [PMID: 25387213 DOI: 10.3810/pgm.2014.11.2832] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND The pleiotropic effects of statins have prompted considerable research in fields other than cardiovascular disease. We reviewed the literature aiming to summarize and critically evaluate the current evidence about the potential use of statins in sepsis. MATERIALS AND METHODS We searched the Pubmed, SciELO, and Cochrane electronic databases from inception through November 1, 2013, for randomized controlled trials (RCTs) and cohort studies that examined the association between statin use (upon hospital admission or previous users) and the risk or outcome of sepsis. Data on study characteristics, measurement of statin use, and outcomes (adjusted for potential confounders) were extracted. We structured our review according to the Principles of Reporting in Systematic Reviews and Meta-Analysis criteria. Quality assessment of cohort studies was performed using the Ottawa-Newcastle Scale. RESULTS Twenty-three cohort studies and 5 RCTs were eligible, comprising 42 549 statin users and 54 201 non-statin users, from 1995 to 2013. The populations included varied from patients admitted to general wards or intensive care units with bacterial infections, community-acquired pneumonia, ventilator-associated pneumonia, bacteremia, or sepsis, to outpatients with chronic kidney disease or established cardiovascular disease. Overall, 16 studies reported a benefit from statin use in morbidity or mortality outcomes (range of adjusted odds ratio, 0.06-0.62; α = 0.05). The remaining 12 studies found no protective effect associated with statin use upon hospital admission or previous users. Among the 5 RCTs, none demonstrated a reduction in mortality. CONCLUSION There is insufficient evidence to support the use of statins in patients with sepsis, as the existing studies failed to prove a consistent mortality benefit. More clinical trials are warranted to provide more conclusive knowledge and ultimately change clinical practice.
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Affiliation(s)
- António Filipe Tralhão
- Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Cardiology, Lisbon, Portugal.
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23
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Mehl A, Harthug S, Lydersen S, Paulsen J, Åsvold BO, Solligård E, Damås JK, Edna TH. Prior statin use and 90-day mortality in Gram-negative and Gram-positive bloodstream infection: a prospective observational study. Eur J Clin Microbiol Infect Dis 2014; 34:609-17. [PMID: 25373530 PMCID: PMC4356896 DOI: 10.1007/s10096-014-2269-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 10/20/2014] [Indexed: 01/31/2023]
Abstract
In several studies on patients with bloodstream infection (BSI), prior use of statins has been associated with improved survival. Gram-positive and Gram-negative bacteria alert the innate immune system in different ways. We, therefore, studied whether the relation between prior statin use and 90-day total mortality differed between Gram-positive and Gram-negative BSI. We conducted a prospective observational cohort study of 1,408 adults with BSI admitted to Levanger Hospital between January 1, 2002, and December 31, 2011. Data on the use of statins and other medications at admission, comorbidities, functional status, treatment, and outcome were obtained from the patients’ hospital records. The relation of statin use with 90-day mortality differed between Gram-negative and Gram-positive BSI (p-value for interaction 0.01). Among patients with Gram-negative BSI, statin users had significantly lower 90-day total mortality [odds ratio (OR) 0.42, 95 % confidence interval (CI) 0.23–0.75, p = 0.003]. The association remained essentially unchanged after adjusting for the effect of sex, age, functional status before the infection, and underlying diseases that were considered confounders (adjusted OR 0.38, 95 % CI 0.20–0.72, p = 0.003). A similar analysis of patients with Gram-positive BSI showed no association of statin use with mortality (adjusted OR 1.22, 95 % CI 0.69–2.17, p = 0.49). The present study suggests that prior statin use is associated with a lower 90-day total mortality in Gram-negative BSI, but not in Gram-positive BSI.
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Affiliation(s)
- A Mehl
- Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Post Box 333, 7601, Levanger, Norway,
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Ye QF, Zhao J, Wan QQ, Qiao BB, Zhou JD. Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality. Transpl Infect Dis 2014; 16:767-774. [PMID: 25124187 DOI: 10.1111/tid.12278] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 04/10/2014] [Accepted: 05/22/2014] [Indexed: 11/27/2022]
Abstract
BACKGROUND Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. RESULTS Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age ≥40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock.
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Affiliation(s)
- Q F Ye
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
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Shao M, Wan Q, Xie W, Ye Q. Bloodstream infections among solid organ transplant recipients: epidemiology, microbiology, associated risk factors for morbility and mortality. Transplant Rev (Orlando) 2014; 28:176-181. [PMID: 24630890 DOI: 10.1016/j.trre.2014.02.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 09/26/2013] [Accepted: 02/09/2014] [Indexed: 12/15/2022]
Abstract
Bloodstream infections (BSIs) remain important causes of morbidity and mortality among solid organ transplant (SOT) recipients and still threaten the success of SOT. In general, among SOT recipients, risk factors for BSIs are associated with prior ICU admission, catheterization, older recipient or donor age…etc. Pulmonary focus, nosocomial source of BSIs, lack of appropriate antibiotic therapy and other variables have significant impacts on BSIs-related mortality in SOT. Most of BSIs in SOT are caused by gram-negative bacteria. However, all aspects including microbiological spectrum, morbidity and mortality rates, risk factors of BSIs and BSIs-related death depend on the type of transplantation. The purpose of this review is to summarize the epidemiology, microbiologic features including antimicrobial resistance of organisms, and associated risk factors for morbidity and mortality of BSIs according to different type of transplantation to better understand the characteristics of BSIs and improve the outcomes after SOT.
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Affiliation(s)
- Mingjie Shao
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China
| | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
| | - Wenzhao Xie
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China
| | - Qifa Ye
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China
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Wan YD, Sun TW, Kan QC, Guan FX, Zhang SG. Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies. Crit Care 2014; 18:R71. [PMID: 24725598 PMCID: PMC4056771 DOI: 10.1186/cc13828] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Accepted: 03/25/2014] [Indexed: 02/01/2023] Open
Abstract
INTRODUCTION Observational data have suggested that statin therapy may reduce mortality in patients with infection and sepsis; however, results from randomized studies are contradictory and do not support the use of statins in this context. Here, we performed a meta-analysis to investigate the effects of statin therapy on mortality from infection and sepsis. METHODS We searched electronic databases (PubMed and Embase) for articles published before November 2013. Randomized or observational studies reporting the effects of statin therapy on mortality in patients with infection or sepsis were eligible. Randomized and observational studies were separately pooled with relative risks (RRs) and random-effects models. RESULTS We examined 5 randomized controlled trials with 867 patients and 27 observational studies with 337,648 patients. Among the randomized controlled trials, statins did not significantly decrease in-hospital mortality (RR, 0.98; 95% confidence interval (CI), 0.73 to 1.33) or 28-day mortality (RR, 0.93; 95% CI, 0.46 to 1.89). However, observational studies indicated that statins were associated with a significant decrease in mortality with adjusted data (RR, 0.65; 95% CI, 0.57 to 0.75) or unadjusted data (RR, 0.74; 95% CI, 0.59 to 0.94). CONCLUSIONS Limited evidence suggests that statins may not be associated with a significant reduction in mortality from infection and sepsis. Although meta-analysis from observational studies showed that the use of statins was associated with a survival advantage, these outcomes were limited by high heterogeneity and possible bias in the data. Therefore, we should be cautious about the use of statins in infection and sepsis.
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Affiliation(s)
- You-Dong Wan
- Department of Integrated ICU, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China
| | - Tong-Wen Sun
- Department of Integrated ICU, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China
| | - Quan-Cheng Kan
- Pharmaceutical Department, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Fang-Xia Guan
- Academy of Medical Science, Henan Province, Zhengzhou, PR China
| | - Shu-Guang Zhang
- Department of Integrated ICU, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450052, China
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López-Cortés LE, Gálvez-Acebal J, del Toro MD, Velasco C, de Cueto M, Caballero FJ, Muniain MA, Pascual Á, Rodríguez-Baño J. Effect of statin therapy in the outcome of bloodstream infections due to Staphylococcus aureus: a prospective cohort study. PLoS One 2013; 8:e82958. [PMID: 24376617 PMCID: PMC3871563 DOI: 10.1371/journal.pone.0082958] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 10/30/2013] [Indexed: 01/12/2023] Open
Abstract
INTRODUCTION Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB). METHODS A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy. RESULTS We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01-0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27-1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10-1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27-2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19-1.29; p = 0.15). CONCLUSIONS Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.
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Affiliation(s)
- Luis E. López-Cortés
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
| | - Juan Gálvez-Acebal
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Medicina, Universidad de Sevilla, Seville, Spain
| | - María D. del Toro
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Medicina, Universidad de Sevilla, Seville, Spain
| | - Carmen Velasco
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Microbiología, Universidad de Sevilla, Seville, Spain
| | - Marina de Cueto
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco J. Caballero
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - Miguel A. Muniain
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Medicina, Universidad de Sevilla, Seville, Spain
| | - Álvaro Pascual
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Microbiología, Universidad de Sevilla, Seville, Spain
| | - Jesús Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain
- Spanish Network for Research in Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Medicina, Universidad de Sevilla, Seville, Spain
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Wan QQ, Ye QF, Ming YZ, Ma Y, Zhou JD, Qiao BB. The risk factors for mortality in deceased donor liver transplant recipients with bloodstream infections. Transplant Proc 2013; 45:305-307. [PMID: 23375319 DOI: 10.1016/j.transproceed.2012.06.080] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 05/09/2012] [Accepted: 06/06/2012] [Indexed: 11/23/2022]
Abstract
BACKGROUND Information on risk factors for mortality among deceased donor liver transplant recipients with bloodstream infections (BSIs) was sought using a retrospective analysis from January 2002 to January 2012. METHODS We performed deceased donor liver transplantations in 135 subjects who experienced 77 episodes of BSIs. We assessed risk factors for mortality among 43 of them using univariate and multivariate logistic regression analysis. RESULTS The 43 recipients (31.9%) who developed BSI showed a mean age of 45.1 (45.1 ± 14.1 years). The majority of infections were nosocomial in origin (97.7%), with more than half being polymicrobial (53.5%). There were 24 deaths among these recipients (55.8%). The univariate analysis identified the following variables as risk factors for BSI-related mortality: polymicrobial (P = .029), platelet count <50,000/mm(3) (P = .02), creatinine > 1.5 mg/dL (P = .008), and septic shock (P < .001). Multivariate logistic regression showed the independent risk factors for mortality to be a serum creatinine > 1.5 mg/dL and septic shock. CONCLUSION The risk factors significantly associated with increased mortality in deceased donor liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Despite appropriate antimicrobial treatment, BSIs accompanied by septic shock or higher serum creatinine levels were associated with high mortality rates. It is therefore essential to protect renal function to reduce the incidence of BSIs.
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Affiliation(s)
- Q Q Wan
- Department of Transplant Surgery, The Third Affiliated Hospital, Central South University, Hunan, China
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Systematic review and meta-analysis on the association between outpatient statins use and infectious disease-related mortality. PLoS One 2012; 7:e51548. [PMID: 23284711 PMCID: PMC3524177 DOI: 10.1371/journal.pone.0051548] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Accepted: 11/02/2012] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND To update and refine systematic literature review on the association between outpatient statins use and mortality in patients with infectious disease. MATERIALS AND METHODS We searched articles published before September 31, 2012, on the association between statins and infectious disease-related mortality through electronic databases. Eligible articles were analyzed in Review Manager 5.1. We conducted stratification analysis by study design, infection types, clinical outcomes and study locations. RESULTS The pooled odds ratio (OR) for death (statins use vs. no use) across the 41 included studies was 0.71 (95% confidence interval: 0.64, 0.78). The corresponding pooled ORs were 0.58 (0.38, 0.90), 0.66 (0.57, 0.75), 0.71 (0.57, 0.89) and 0.83 (0.67, 1.04) for the case-control study, retrospective cohort studies, prospective cohort studies and RCTs; 0.40 (0.20, 0.78), 0.61 (0.41, 0.90), 0.69 (0.62, 0.78) and 0.86 (0.68, 1.09) for bacteremia, sepsis, pneumonia and other infections; 0.62 (0.534, 0.72), 0.68 (0.53, 0.89), 0.71 (0.61, 0.83) and 0.86 (0.70, 1.07) for 30-day, 90-day, in-hospital and long-term (>1 year) mortality, respectively. CONCLUSIONS Outpatient statins use is associated with a lower risk of death in patients with infectious disease in observational studies, but in a less extent in clinical trials. This association also varies considerably by infection types and clinical outcomes.
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30
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De Loecker I, Preiser JC. Statins in the critically ill. Ann Intensive Care 2012; 2:19. [PMID: 22709377 PMCID: PMC3488539 DOI: 10.1186/2110-5820-2-19] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2012] [Accepted: 04/26/2012] [Indexed: 12/23/2022] Open
Abstract
The use or misuse of statins in critically ill patients recently attracted the attention of intensive care clinicians. Indeed, statins are probably the most common chronic treatment before critical illness and some recent experimental and clinical data demonstrated their beneficial effects during sepsis, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), or after aneurismal subarachnoidal hemorrhage (aSAH). Due to the heterogeneity of current studies and the lack of well-designed prospective studies, definitive conclusions for systematic and large-scale utilization in intensive care units cannot be drawn from the published evidence. Furthermore, the extent of statins side effects in critically ill patients is still unknown. For the intensive care clinician, it is a matter of individually identifying the patient who can benefit from this therapy according to the current literature. The purpose of this review is to describe the mechanisms of actions of statins and to synthesize the clinical data that underline the relevant effects of statins in the particular setting of critical care, in an attempt to guide the clinician through his daily practice.
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Affiliation(s)
- Isabelle De Loecker
- Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070, Brussels, Belgium
| | - Jean-Charles Preiser
- Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070, Brussels, Belgium
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31
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Statins for sepsis. Crit Care Med 2012; 40:1336-7. [DOI: 10.1097/ccm.0b013e3182410308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Singh PP, Srinivasa S, Lemanu DP, MacCormick AD, Hill AG. Statins in Abdominal Surgery: A Systematic Review. J Am Coll Surg 2012; 214:356-66. [DOI: 10.1016/j.jamcollsurg.2011.11.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2011] [Revised: 11/18/2011] [Accepted: 11/21/2011] [Indexed: 12/14/2022]
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Mihos CG, Santana O. Pleiotropic effects of the HMG-CoA reductase inhibitors. Int J Gen Med 2011; 4:261-71. [PMID: 21556312 PMCID: PMC3085235 DOI: 10.2147/ijgm.s16779] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2011] [Indexed: 12/19/2022] Open
Abstract
The HMG-CoA reductase inhibitors (statins) are used extensively in the treatment of hyperlipidemia. They have also demonstrated a benefit in a variety of other disease processes. These secondary actions are known as pleiotropic effects. Our paper serves as a focused and updated discussion on the pleiotropy of statins and emphasizes the importance of randomized placebo-controlled trials to further elucidate this interesting phenomenon.
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Affiliation(s)
- Christos G Mihos
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
| | - Orlando Santana
- Columbia University Division of Cardiology, Mount Sinai Heart Institute, Miami Beach, FL, USA
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Kouroumichakis I, Papanas N, Proikaki S, Zarogoulidis P, Maltezos E. Statins in prevention and treatment of severe sepsis and septic shock. Eur J Intern Med 2011; 22:125-33. [PMID: 21402241 DOI: 10.1016/j.ejim.2010.12.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2010] [Revised: 10/28/2010] [Accepted: 12/07/2010] [Indexed: 12/13/2022]
Abstract
Severe sepsis is an infection-induced inflammatory syndrome that can lead to multi-organ dysfunction and continues to be a major cause of morbidity and mortality worldwide. Because numerous cascades are triggered during sepsis, selective blocking of inflammatory mediators may be insufficient to arrest this process, and recent therapeutic approaches have proven controversial. Statins are the most commonly prescribed agents for hypercholesterolaemia and dominate the area of cardiovascular risk reduction. Moreover, these drugs have a variety of actions that are independent of their lipid lowering effect. Such anti-inflammatory, antioxidant, immunomodulatory, and antiapoptotic features have been collectively referred to as pleiotropic effects. By virtue of their pleiotropic effects, statins have also emerged as potentially useful in various critical care areas such as bacteraemia, the early phases of sepsis and septic shock, as well as the management of serious infections. This review outlines current evidence on the use of statins for preventing and treating sepsis.
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Affiliation(s)
- I Kouroumichakis
- Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
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Lorente L, Martín MM, Varo N, Borreguero-León JM, Solé-Violán J, Blanquer J, Labarta L, Díaz C, Jiménez A, Pastor E, Belmonte F, Orbe J, Rodríguez JA, Gómez-Melini E, Ferrer-Agüero JM, Ferreres J, LLimiñana MC, Páramo JA. Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis. Crit Care 2011; 15:R97. [PMID: 21406105 PMCID: PMC3219362 DOI: 10.1186/cc10104] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2010] [Revised: 02/17/2011] [Accepted: 03/15/2011] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. METHODS This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. RESULTS Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). CONCLUSIONS In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.
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Affiliation(s)
- Leonardo Lorente
- Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
| | - María M Martín
- Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Crta del Rosario s/n, Santa Cruz de Tenerife - 38010, Spain
| | - Nerea Varo
- Biochemistry Deparment, Clínica Universidad de Navarra, Avda Pío XII n°55, Pamplona - 31008, Spain
| | - Juan María Borreguero-León
- Laboratory Deparment, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
| | - Jordi Solé-Violán
- Intensive Care Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, Las Palmas de Gran Canaria - 35010, Spain
| | - José Blanquer
- Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avda. Blasco Ibáñez no. 17-19, Valencia - 46004, Spain
| | - Lorenzo Labarta
- Intensive Care Unit, Hospital San Jorge de Huesca, Avenida Martínez de Velasco n°36, Huesca - 22004, Spain
| | - César Díaz
- Intensive Care Unit, Hospital Insular, Plaza Dr. Pasteur s/n, Las Palmas de Gran Canaria - 35016, Spain
| | - Alejandro Jiménez
- Mixed Research Unit HUC-ULL, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
| | - Eduardo Pastor
- Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
| | - Felipe Belmonte
- Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Crta del Rosario s/n, Santa Cruz de Tenerife - 38010, Spain
| | - Josune Orbe
- Atherosclerosis Research Laboratory, CIMA-University of Navarra, Avda Pío XII no. 55, Pamplona - 31008, Spain
| | - José A Rodríguez
- Atherosclerosis Research Laboratory, CIMA-University of Navarra, Avda Pío XII no. 55, Pamplona - 31008, Spain
| | - Eduardo Gómez-Melini
- Laboratory Deparment, Hospital Universitario de Canarias, Ofra, s/n, La Laguna - 38320, Santa Cruz de Tenerife, Spain
| | - José M Ferrer-Agüero
- Intensive Care Unit, Hospital Universitario Dr. Negrín, Barranco de la Ballena s/n, Las Palmas de Gran Canaria - 35010, Spain
| | - José Ferreres
- Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avda. Blasco Ibáñez no. 17-19, Valencia - 46004, Spain
| | - María C LLimiñana
- Laboratory Department, Hospital San Jorge de Huesca, Avenida Martínez de Velasco no. 36, Huesca - 22004, Spain
| | - José A Páramo
- Atherosclerosis Research Laboratory, CIMA-University of Navarra, Avda Pío XII no. 55, Pamplona - 31008, Spain
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Viasus D, Gudiol C, Fernández-Sabé N, Cabello I, Garcia-Vidal C, Cisnal M, Duarte R, Antonio M, Carratalà J. Effect of statins on outcomes in immunosuppressed patients with bloodstream infection. Eur J Clin Microbiol Infect Dis 2010; 30:77-82. [DOI: 10.1007/s10096-010-1056-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2010] [Accepted: 08/23/2010] [Indexed: 11/29/2022]
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Björkhem-Bergman L, Bergman P, Andersson J, Lindh JD. Statin treatment and mortality in bacterial infections--a systematic review and meta-analysis. PLoS One 2010; 5:e10702. [PMID: 20502712 PMCID: PMC2873291 DOI: 10.1371/journal.pone.0010702] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2010] [Accepted: 04/28/2010] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Several studies have reported improved survival in severe bacterial infections among statin treated patients. In addition, statins have been ascribed beneficial anti-inflammatory effects. The aim of this study was to evaluate the effect of statin-treatment on mortality in patients with bacterial infections, by means of a systematic review and a meta-analysis. METHODOLOGY AND PRINCIPAL FINDINGS Studies investigating the association between statin use and mortality in patients with bacterial disease were identified in a systematic literature review and a meta-analysis was performed to calculate the overall odds ratio of mortality in statin users. The literature search identified 947 citations from which 40 relevant studies were extracted. In all, 15 studies comprising 113,910 patients were included in the final analysis. Statin use was associated with a significantly (p<0.0001) reduced mortality in patients suffering from bacterial infections (OR 0.52, 95% CI 0.42-0.66). However, all studies included were of observational design and funnel plot analyses indicated influence by a possible publication bias (Egger's bias test p<0.05). When a precision estimate test was used to adjust for publication bias the effect of statin treatment was no longer significant, with an OR of 0.79 (95% CI 0.58-1.07). CONCLUSION/SIGNIFICANCE According to the meta-analysis of observational studies presented here, patients on statin therapy seem to have a better outcome in bacterial infections. However, the association did not reach statistical significance after adjustment for apparent publication bias. Thus, there is a great need for randomised controlled trials investigating the possible beneficial effect of statins in bacterial infections.
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Affiliation(s)
- Linda Björkhem-Bergman
- Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
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Janda S, Young A, Fitzgerald JM, Etminan M, Swiston J. The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. J Crit Care 2010; 25:656.e7-22. [PMID: 20413251 DOI: 10.1016/j.jcrc.2010.02.013] [Citation(s) in RCA: 137] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2009] [Revised: 02/14/2010] [Accepted: 02/26/2010] [Indexed: 01/12/2023]
Abstract
PURPOSE The aim of this study was to systematically review the literature on the effect of statins on mortality in patients with infection and/or sepsis. MATERIALS AND METHODS MEDLINE, EMBASE, PapersFirst, and the Cochrane collaboration and the Cochrane Register of controlled trials were searched and were current as of December 2009. Randomized, double-blind or single-blind, placebo-controlled studies; observational cohort studies (retrospective and prospective); and case-controlled studies were included. Types of participants included adult and pediatric subjects with sepsis or various other types of infection. Exposure was defined as the use of a statin for any indication. The primary outcome chosen was mortality from any cause, and secondary outcomes included 30-day mortality, in-hospital mortality, mortality from pneumonia, mortality from bacteremia, mortality from sepsis, and mortality from mixed infection. RESULTS A total of 20 studies were included in the analysis, 18 being cohort studies (12 retrospective, 6 prospective), 1 matched cohort study with 2 case-control studies, and 1 randomized control trial. Meta-analysis for various infection-related outcomes revealed the following pooled odds ratios all in favor of statin use vs non: 0.61 (95% confidence interval [CI], 0.48-0.73) for 30-day mortality (n = 7), 0.38 (95% CI, 0.13-0.64) for in-hospital mortality (n = 7), 0.63 (95% CI, 0.55-0.71) for pneumonia-related mortality (n = 7), 0.33 (95% CI, 0.09-0.75) for bacteremia-related mortality (n = 4), 0.40 (95% CI, 0.23-0.57) for sepsis-related mortality (n = 4), and 0.50 (95% CI, 0.18-0.83) for mixed infection-related mortality (n = 4). CONCLUSIONS This meta-analysis demonstrated a protective effect for statins in patients with sepsis and/or other infections compared to placebo for various infection-related outcomes. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them, and as a result, further randomized trials are needed to validate the use of statins for sepsis and/or other infections.
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Affiliation(s)
- Surinder Janda
- University of British Columbia, Vancouver, British Columbia, Canada.
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