Polymyxins: “Last Resort” for MDR and/or XDR Gram-Negative Infections

Abstract
Polymyxins were used for the management of gram-negative infections in clinical practice science1940s. Parenteral administration waned in the seventies owing to polymyxins nephrotoxicity and neurotoxicity. Because of the lack of treatment choices for MDR and/or XDRgram negative superbugs as well as Acinetobacter baumannii, Klebsiella pneumonia, and Pseudomonas aeruginosa, there is a growing need for effective prescribing of old antibiotics that are still effective. However, understanding of polymyxins pharmacokinetics (PK) was restricted and clinical experience is limited which leads to a lack of widespread availability of up-to-date dosing guidelines that could potentially result in the incorrect use of these “last resort” antibiotics. Recently, polymyxin B resistant strains are also a reason of concern. In this review, we discuss the importance of preserving the effectiveness of polymyxins for nosocomial gram-negative infections and strategies to improve polymyxins’ prescription. We recommend that polymyxins should only be used to manage significant MDR and/or XDRgram-negative infections, in optimum doses and if possible, in combination therapy