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J Antimicrob Chemother. 2014 Sep;69(9):2305-9. doi: 10.1093/jac/dku168. Epub 2014 May 28.

Combination therapy for carbapenem-resistant Gram-negative bacteria.

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Division of Infectious Diseases, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
Division of Epidemiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
Internal Medicine, University of Naples S.U.N., Monaldi Hospital, Napoli, Italy.
Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Infectious Diseases and Internal Medicine I, Tuebingen University Hospital, Tuebingen, Germany.
Center for Anti-Infective Agents, Vienna, Austria.
Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.


Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing hazard in healthcare settings. A central question concerning the treatment of invasive infections caused by CR-GNB involves the use of combination therapy. Potential advantages of combination therapy include improved efficacy due to synergy, while the disadvantages include adverse events and increased antibiotic use with a potential drive towards resistance. Several observational studies have examined whether combination therapy offers an advantage over colistin/polymyxin monotherapy. We highlight the inherent limitations of these studies related to their observational design and sample size to show why they do not at present provide an answer to the question of combination versus monotherapy. This distinction is important to guide clinical practice until solid evidence has been obtained and to enable the recruitment of patients into randomized controlled trials. A few randomized controlled trials examining specific combinations have recently been completed or are ongoing. Currently, however, there is no evidence-based support for most combination therapies against CR-GNB, including colistin/carbapenem combination therapy.


Acinetobacter baumannii; Klebsiella pneumonia; carbapenem-resistant Enterobacteriaceae; carbapenems; colistin

[Indexed for MEDLINE]

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