title: Combination therapy for carbapenem-resistant Gram-negative bacteria.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Rambam Health Care Campus and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel paulm@post.tau.ac.il.
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
authors.affiliation: Division of Epidemiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.affiliation: Internal Medicine, University of Naples S.U.N., Monaldi Hospital, Napoli, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.affiliation: Infectious Diseases and Internal Medicine I, Tuebingen University Hospital, Tuebingen, Germany.
authors.forename: Evelina
authors.initials: E
authors.lastname: Tacconelli
authors.affiliation: Center for Anti-Infective Agents, Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Theuretzbacher
authors.affiliation: Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000379:methods; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: Acinetobacter baumannii; Klebsiella pneumonia; carbapenem-resistant Enterobacteriaceae; carbapenems; colistin