Akosua A Agyeman1, Phillip J Bergen1, Gauri G Rao2, Roger L Nation3, Cornelia B Landersdorfer4. 1. Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria, Australia. 2. UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. 3. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria, Australia. 4. Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria, Australia. Electronic address: cornelia.landersdorfer@monash.edu.
Abstract
INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major global public health challenge. This study aimed to systematically review the evidence on treatment outcomes (mortality, clinical and microbiological response) following antibiotic therapy administered for CRKP infections. METHODS: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts databases were searched from inception to 26 December 2018. Data were analysed via meta-analysis techniques using random-effects (DerSimonian and Laird) modelling. RESULTS: Fifty-four observational studies involving 3195 CRKP-infected patients who received antibiotic treatment were included. The pooled mortality, clinical and microbiological response rates were 37.2% (95% confidence interval [CI] 33.1-41.4%), 69.0% (95% CI 60.1-78.2%) and 63.7% (95% CI 53.7-74.1%), respectively. Compared with combination therapy, monotherapy was associated with a higher likelihood of mortality (odds ratio [OR] 1.45, 95% CI 1.18-1.78%), but there were no statistically significant differences in the likelihood of achieving clinical and microbiological responses. There were no statistically significant differences in the pooled likelihood of mortality, clinical or microbiological responses between two-drug and three-or-more-drug combination therapies or combination-containing and combination-sparing regimens of polymyxins, tigecycline, aminoglycosides and carbapenems. Moreover, clinical outcomes did not significantly differ among the various monotherapies. CONCLUSIONS: These data highlight the need for systematic studies and well-designed randomised clinical trials to identify and evaluate the most appropriate antibiotic therapies for CRKP infections towards informing clinical decision-making. Furthermore, continuous surveillance of antimicrobial susceptibility patterns at local, regional, and national/international levels are important to support empirically-based therapy until susceptibility results for the isolate from the patient are available.
INTRODUCTION:Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major global public health challenge. This study aimed to systematically review the evidence on treatment outcomes (mortality, clinical and microbiological response) following antibiotic therapy administered for CRKP infections. METHODS: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts databases were searched from inception to 26 December 2018. Data were analysed via meta-analysis techniques using random-effects (DerSimonian and Laird) modelling. RESULTS: Fifty-four observational studies involving 3195 CRKP-infected patients who received antibiotic treatment were included. The pooled mortality, clinical and microbiological response rates were 37.2% (95% confidence interval [CI] 33.1-41.4%), 69.0% (95% CI 60.1-78.2%) and 63.7% (95% CI 53.7-74.1%), respectively. Compared with combination therapy, monotherapy was associated with a higher likelihood of mortality (odds ratio [OR] 1.45, 95% CI 1.18-1.78%), but there were no statistically significant differences in the likelihood of achieving clinical and microbiological responses. There were no statistically significant differences in the pooled likelihood of mortality, clinical or microbiological responses between two-drug and three-or-more-drug combination therapies or combination-containing and combination-sparing regimens of polymyxins, tigecycline, aminoglycosides and carbapenems. Moreover, clinical outcomes did not significantly differ among the various monotherapies. CONCLUSIONS: These data highlight the need for systematic studies and well-designed randomised clinical trials to identify and evaluate the most appropriate antibiotic therapies for CRKP infections towards informing clinical decision-making. Furthermore, continuous surveillance of antimicrobial susceptibility patterns at local, regional, and national/international levels are important to support empirically-based therapy until susceptibility results for the isolate from the patient are available.
Authors: Minggui Wang; Michelle Earley; Liang Chen; Blake M Hanson; Yunsong Yu; Zhengyin Liu; Soraya Salcedo; Eric Cober; Lanjuan Li; Souha S Kanj; Hainv Gao; Jose M Munita; Karen Ordoñez; Greg Weston; Michael J Satlin; Sandra L Valderrama-Beltrán; Kalisvar Marimuthu; Martin E Stryjewski; Lauren Komarow; Courtney Luterbach; Steve H Marshall; Susan D Rudin; Claudia Manca; David L Paterson; Jinnethe Reyes; Maria V Villegas; Scott Evans; Carol Hill; Rebekka Arias; Keri Baum; Bettina C Fries; Yohei Doi; Robin Patel; Barry N Kreiswirth; Robert A Bonomo; Henry F Chambers; Vance G Fowler; Cesar A Arias; David van Duin Journal: Lancet Infect Dis Date: 2021-11-09 Impact factor: 25.071