Abstract
Polymyxins have been a mainstay for the treatment of extensively drug resistant (XDR) Gram-negative bacteria for the past two decades. Many questions regarding the clinical use of polymyxins have been answered, but whether the administration of polymyxins in combination with other antibiotics leads to better outcomes remains unknown. This review discusses the limitations of observational studies that suggest a benefit of combinations of colistin and carbapenems to treat infections caused by carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, and summarizes the results of randomized controlled trials in which treatment with colistin in combination with meropenem or rifampin does not lead to better clinical outcomes than colisitn monotherapy in infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). Although the introduction of new antibiotics makes it possible to treat certain strains of CRE and carbapenem-resistant P. aeruginosa (CRPA) with polymyxin-sparing regimens, the use of polymyxins is, for now, still necessary in CRAB and in CRE and CRPA harboring metallo-beta-lactamases. Therefore, strategies must be developed to optimize polymyxin-based treatments, informed by in vitro hollow fiber models, careful clinical observations, and high-quality evidence from appropriately designed trials.
Highlights
Polymyxins are cationic antimicrobial polypeptides that bind to negatively charged phosphate moieties in the lipid A fraction of lipopolysaccharide (LPS) present in the outer membrane ofGram-negative bacteria
Incorporating the INCREMENT-CPE score into the analysis revealed that combination therapy was associated with lower mortality (48%) than monotherapy (62%) in the high-mortality-score stratum only
Despite the paucity of high-quality evidence supporting the superiority of polymyxin-based combination therapy vs. polymyxin monotherapy, clinicians who rely on polymyxins to treat serious infections caused by XDR Gram-negative bacteria often employ them in combination with other antibiotics
Summary
Polymyxins are cationic antimicrobial polypeptides that bind to negatively charged phosphate moieties in the lipid A fraction of lipopolysaccharide (LPS) present in the outer membrane of. Polymyxins act by disrupting the bacterial cell membrane; this process results in the loss of intracellular products, leading to bactericidal activity. The two examples of polymyxins used in the clinic, polymyxin B and polymyxin E (i.e., colistin), were introduced in the 1950s without the scrutiny of regulatory agencies. The toxicity profile and the subsequent development of aminoglycosides and cephalosporins relegated polymyxins to a Antibiotics 2019, 8, 38; doi:10.3390/antibiotics8020038 www.mdpi.com/journal/antibiotics. Polymyxins were “resurrected” at the end of the 20th century to address the therapeutic challenge posed by emergent extensively drug resistant (XDR) Gram-negative bacteria, especially carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant. Enterobacteriaceae (CRE), and carbapenem-resistant Acinetobacter baumannii (CRAB) [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
