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Karaaslan E, Oyardi O, Dosler S. Enhancing colistin efficacy with combination therapies for multidrug-resistant P. aeruginosa and A. baumannii isolates. Future Microbiol 2025; 20:523-531. [PMID: 40208781 DOI: 10.1080/17460913.2025.2490377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 04/04/2025] [Indexed: 04/12/2025] Open
Abstract
AIM Increasing resistance among ESKAPEEc pathogens, particularly Acinetobacter baumannii and Pseudomonas aeruginosa, has necessitated the use of last-resort antibiotics such as colistin. This study aimed to evaluate the effectiveness and reveal a dynamic picture of colistin-based combination therapies. MATERIALS & METHODS This study evaluated the in vitro efficacy of colistin in combination with doxycycline, doripenem, and rifampicin against multidrug-resistant clinical isolates of P. aeruginosa (n = 23) and A. baumannii (n = 26). Susceptibility testing performed by microbroth dilution method, and synergistic interactions were assessed via checkerboard and time-kill curve (TKC) assays. RESULTS All isolates were resistant to colistin, according to their MICs. In checkerboard assays, according to synergism rates, colistin-doripenem and colistin-doxycycline combinations were particularly effective. The degrees of synergy for doripenem, doxycycline, and rifampicin were 30%, 90%, and 20%, respectively, against P. aeruginosa, and 30%, 60%, and 30%, respectively, against A. baumannii. In TKC analysis, synergistic interactions are generally observed with colistin at 1/4×MIC or 1×MIC, and indifference effects at 4×MIC, similar to colistin monotherapy. TKCs also confirmed the bactericidal activities of combinations that achieved ≥3-log10 reductions in initial bacterial counts. CONCLUSIONS Colistin-based combination therapies, especially colistin-doripenem, may be promising approaches for combating multidrug-resistant pathogens while potentially reducing nephrotoxicity risk.
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Affiliation(s)
- Elif Karaaslan
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye
| | - Ozlem Oyardi
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Gazi University, Ankara, Türkiye
| | - Sibel Dosler
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul, Türkiye
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2
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Abstract
Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of "safer" antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative "superbugs," every effort must be made to improve the clinical utility of the last-line polymyxins. SIGNIFICANCE STATEMENT: Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.
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Affiliation(s)
- Sue C Nang
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Mohammad A K Azad
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Tony Velkov
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Qi Tony Zhou
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
| | - Jian Li
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia (S.C.N., M.A.K.A., J.L.); Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia (T.V.); and Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana (Q.T.Z.)
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Shafiekhani M, Mirjalili M, Vazin A. Prevalence, Risk Factors And Treatment Of The Most Common Gram-Negative Bacterial Infections In Liver Transplant Recipients: A Review. Infect Drug Resist 2020; 12:3485-3495. [PMID: 32009806 PMCID: PMC6859291 DOI: 10.2147/idr.s226217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 10/10/2019] [Indexed: 11/23/2022] Open
Abstract
Advances in surgical techniques and immunosuppressive agents have made solid organ transplant (Tx) an important strategy for treatment of end-stage organ failures. However, the incidence of infections following Tx due to Gram-negative pathogens is on the rise. These infections are associated with increased mortality and morbidity in patients following transplantation, including liver Tx. Thus, managing infections in liver Tx recipients is a big challenge, requiring prompt medical attention. Considering the important effect of Gram-negative bacterial infections on the outcomes of liver Tx recipients, the most prevalent Gram-negative pathogens including Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli will be discussed in this review.
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Affiliation(s)
- Mojtaba Shafiekhani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.,Shiraz Organ Transplant Center, Abu-Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahtabalsadat Mirjalili
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afsaneh Vazin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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Bergen PJ, Smith NM, Bedard TB, Bulman ZP, Cha R, Tsuji BT. Rational Combinations of Polymyxins with Other Antibiotics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1145:251-288. [PMID: 31364082 DOI: 10.1007/978-3-030-16373-0_16] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Combinations of antimicrobial agents are often used in the management of infectious diseases. Antimicrobial agents used as part of combination therapy are often selected empirically. As regrowth and the emergence of polymyxin (either colistin or polymyxin B) resistance has been observed with polymyxin monotherapy, polymyxin combination therapy has been suggested as a possible means by which to increase antimicrobial activity and reduce the development of resistance. This chapter provides an overview of preclinical and clinical investigations of CMS/colistin and polymyxin B combination therapy. In vitro data and animal model data suggests a potential clinical benefit with many drug combinations containing clinically achievable concentrations of polymyxins, even when resistance to one or more of the drugs in combination is present and including antibiotics normally inactive against Gram-negative organisms. The growing body of data on the emergence of polymyxin resistance with monotherapy lends theoretical support to a benefit with combination therapy. Benefits include enhanced bacterial killing and a suppression of polymyxin resistant subpopulations. However, the complexity of the critically ill patient population, and high rates of treatment failure and death irrespective of infection-related outcome make demonstrating a potential benefit for polymyxin combinations extremely challenging. Polymyxin combination therapy in the clinic remains a heavily debated and controversial topic. When combinations are selected, optimizing the dosage regimens for the polymyxin and the combinatorial agent is critical to ensure that the benefits outweigh the risk of the development of toxicity. Importantly, patient characteristics, pharmacokinetics, the site of infection, pathogen and resistance mechanism must be taken into account to define optimal and rational polymyxin combination regimens in the clinic.
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Affiliation(s)
- Phillip J Bergen
- Centre for Medicine Use and Safety, Monash University, Parkville Campus, Melbourne, VIC, Australia.
| | - Nicholas M Smith
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Tyler B Bedard
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Zackery P Bulman
- University of Illinois Chicago, College of Pharmacy, Chicago, IL, USA
| | - Raymond Cha
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Brian T Tsuji
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
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Liu T, Zhang Y, Wan Q. Pseudomonas aeruginosa bacteremia among liver transplant recipients. Infect Drug Resist 2018; 11:2345-2356. [PMID: 30532566 PMCID: PMC6247952 DOI: 10.2147/idr.s180283] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Pseudomonas aeruginosa bacteremia remains as a life-threatening complication after liver transplantation (LT) and is intractable because of the high rate of drug resistance to commonly used antibiotics. To better understand the characteristics of this postoperative complication, PubMed and Embase searches as well as reference mining was done for relevant literature from the start of the databases through August 2018. Among LT recipients, the incidence of P. aeruginosa bacteremia ranged from 0.5% to 14.4% and mortality rates were up to 40%. Approximately 35% of all episodes of bloodstream infections (BSIs) were P. aeruginosa bacteremia, of which 47% were multidrug resistant and 63% were extensively drug resistant. Several factors are known to affect the mortality of LT recipients with P. aeruginosa bacteremia, including hypotension, mechanical ventilation, and increasing severity of illness. In LT recipients with P. aeruginosa bacteremia, alteration in DNA gyrase A genes and overexpression of proteins involved in efflux systems, namely the expression of KPC-2-type carbapenemase, NDM-1, and VIM-2-type MBL, contribute to the high resistance of P. aeruginosa to a wide variety of antibiotics. Because of complicated mechanisms of drug resistance, P. aeruginosa causes high morbidity and mortality in bacteremic LT patients. Consequently, early detection and treatment with adequate early targeted coverage for P. aeruginosa BSI are of paramount importance in the early posttransplantation period to obtain a better prognosis for LT patients.
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Affiliation(s)
- Taohua Liu
- Xiangya School of Medicine, Central South University, Changsha 410083, China
| | - Yuezhong Zhang
- Xiangya School of Medicine, Central South University, Changsha 410083, China
| | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China,
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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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Bergen PJ, Bulman ZP, Landersdorfer CB, Smith N, Lenhard JR, Bulitta JB, Nation RL, Li J, Tsuji BT. Optimizing Polymyxin Combinations Against Resistant Gram-Negative Bacteria. Infect Dis Ther 2015; 4:391-415. [PMID: 26645096 PMCID: PMC4675771 DOI: 10.1007/s40121-015-0093-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Indexed: 01/01/2023] Open
Abstract
Polymyxin combination therapy is increasingly used clinically. However, systematic investigations of such combinations are a relatively recent phenomenon. The emerging pharmacodynamic (PD) and pharmacokinetic (PK) data on CMS/colistin and polymyxin B suggest that caution is required with monotherapy. Given this situation, polymyxin combination therapy has been suggested as a possible way to increase bacterial killing and reduce the development of resistance. Considerable in vitro data have been generated in support of this view, particularly recent studies utilizing dynamic models. However, most existing animal data are of poor quality with major shortcomings in study design, while clinical data are generally limited to retrospective analysis and small, low-power, prospective studies. This article provides an overview of clinical and preclinical investigations of CMS/colistin and polymyxin B combination therapy.
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Affiliation(s)
- Phillip J Bergen
- Centre for Medicine Use and Safety, Monash University, Melbourne, Australia
| | - Zackery P Bulman
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Cornelia B Landersdorfer
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia.,Centre for Medicine Use and Safety, Monash University, Melbourne, Australia
| | - Nicholas Smith
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Justin R Lenhard
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA
| | - Jürgen B Bulitta
- Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA
| | - Roger L Nation
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia
| | - Jian Li
- Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia
| | - Brian T Tsuji
- Laboratory for Antimicrobial Pharmacodynamics, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA.
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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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Gao F, Ye Q, Wan Q, Liu S, Zhou J. Distribution and resistance of pathogens in liver transplant recipients with Acinetobacter baumannii infection. Ther Clin Risk Manag 2015. [PMID: 25848296 DOI: 10.2147/tcrm.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Drug-resistant Acinetobacter baumannii has become a major problem in liver transplant recipients. The aim of this study was to investigate the clinical presentation, distribution, and drug susceptibility characteristics in liver recipients with A. baumannii infection. METHODS We retrospectively investigated 17 liver recipients who developed A. baumannii infection between January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug susceptibility characteristics were reviewed. RESULTS Infectious complications due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes. Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks after transplantation. The most common source of infection was multiple culture-positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature of 38°C or higher at the onset of A. baumannii infection. Nine, seven, and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell count of >15,000/mm(3), and a platelet count of <50,000/mm(3), respectively. There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated was more than 60%. Among the 24 infections caused by A. baumannii, 75% were carbapenem-resistant. The rods were relatively sensitive to tigecycline and cefoperazone-sulbactam. CONCLUSION The clinical manifestations of A. baumannii infection included a high body temperature, a decreased platelet count, an elevated white blood cell count, and onset in the early period after transplantation as well as high mortality. The antibiotic resistance rate of A. baumannii was extremely high. Prevention measures and combination antibiotic therapy are needed to improve the outcomes of liver recipients with A. baumannii infections.
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Affiliation(s)
- Fei Gao
- Infectious Disease Department of Henan Province People's Hospital, Zhengzhou, People's Republic of China
| | - Qifa Ye
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China ; Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China
| | - Qiquan Wan
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Shan Liu
- Adelphi University College of Nursing and Public Health, New York, NY, USA
| | - Jiandang Zhou
- Department of Clinical Laboratory of Microbiology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China
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Gao F, Ye Q, Wan Q, Liu S, Zhou J. Distribution and resistance of pathogens in liver transplant recipients with Acinetobacter baumannii infection. Ther Clin Risk Manag 2015; 11:501-505. [PMID: 25848296 PMCID: PMC4381901 DOI: 10.2147/tcrm.s82251] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Drug-resistant Acinetobacter baumannii has become a major problem in liver transplant recipients. The aim of this study was to investigate the clinical presentation, distribution, and drug susceptibility characteristics in liver recipients with A. baumannii infection. METHODS We retrospectively investigated 17 liver recipients who developed A. baumannii infection between January 1, 2007 and December 31, 2014. The distribution of A. baumannii and drug susceptibility characteristics were reviewed. RESULTS Infectious complications due to A. baumannii appeared in 17 liver recipients, with a total of 24 episodes. Approximately 63% (15/24) of A. baumannii infections occurred within 2 weeks after transplantation. The most common source of infection was multiple culture-positive sites (35.3%, n=6), followed by the intra-abdominal/biliary tract (23.5%, n=4) and lung (23.5%, n=4). Eight patients (47.1%) had a body temperature of 38°C or higher at the onset of A. baumannii infection. Nine, seven, and 12 recipients had a serum creatinine level of >1.5 mg/dL, a white blood cell count of >15,000/mm(3), and a platelet count of <50,000/mm(3), respectively. There were five (29.4%) cases of septic shock and eight (47.1%) deaths. The rate of antibiotic resistance of A. baumannii to ten of 12 antibiotics investigated was more than 60%. Among the 24 infections caused by A. baumannii, 75% were carbapenem-resistant. The rods were relatively sensitive to tigecycline and cefoperazone-sulbactam. CONCLUSION The clinical manifestations of A. baumannii infection included a high body temperature, a decreased platelet count, an elevated white blood cell count, and onset in the early period after transplantation as well as high mortality. The antibiotic resistance rate of A. baumannii was extremely high. Prevention measures and combination antibiotic therapy are needed to improve the outcomes of liver recipients with A. baumannii infections.
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Affiliation(s)
- Fei Gao
- Infectious Disease Department of Henan Province People’s Hospital, Zhengzhou, People’s Republic of China
| | - Qifa Ye
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China
- Department of Transplant Surgery, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China
| | - Qiquan Wan
- Department of Transplant Surgery, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China
| | - Shan Liu
- Adelphi University College of Nursing and Public Health, New York, NY, USA
| | - Jiandang Zhou
- Department of Clinical Laboratory of Microbiology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China
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11
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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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Santoro-Lopes G, Gouvêa EFD. Multidrug-resistant bacterial infections after liver transplantation: An ever-growing challenge. World J Gastroenterol 2014; 20:6201-6210. [PMID: 24876740 PMCID: PMC4033457 DOI: 10.3748/wjg.v20.i20.6201] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/20/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients. Over the last two decades, various multidrug-resistant (MDR) pathogens have emerged as relevant causes of infection in this population. Although this fact reflects the spread of MDR pathogens in health care facilities worldwide, several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units. The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy, which further contributes to the selection of drug resistance. This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options. Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial therapy. The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections. Furthermore, high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens, such as carbapenem-resistant Enterobacteriaceae, for which optimal treatment remains undefined. In such a context, the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients. This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients, and summarizes current preventive and therapeutic recommendations.
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Patel G, Rana MM, Huprikar S. Multidrug-resistant bacteria in organ transplantation: an emerging threat with limited therapeutic options. Curr Infect Dis Rep 2013; 15:504-13. [PMID: 24101302 DOI: 10.1007/s11908-013-0371-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Multidrug-resistant organisms (MDROs) are an emerging threat in solid organ transplantation (SOT). The changing epidemiology of these MDROs is reviewed along with the growing evidence regarding risk factors and outcomes associated with both colonization and infection in SOT. The management of these infections is complicated by the lack of antimicrobial agents available to treat these infections, and only a handful of new agents, especially for the treatment of MDR GNR infections, are being evaluated in clinical trials. Due to the increased prevalence of MDROs and limited treatment options, as well as organ shortages, transplant candidacy and use of organs from donors with evidence of MDRO colonization and/or infection remain controversial. Increasing collaboration between transplant programs, individual practitioners, infection control programs, and researchers in antimicrobial development will be needed to face this challenge.
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Affiliation(s)
- Gopi Patel
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA,
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van Duin D, van Delden C. Multidrug-resistant gram-negative bacteria infections in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:31-41. [PMID: 23464996 DOI: 10.1111/ajt.12096] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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