Combination therapy for carbapenem-resistant Gram-negative bacteria

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.