Polymyxins for the treatment of lower respiratory tract infections: lessons learned from the integration of clinical pharmacokinetic studies and clinical outcomes

The global rise in nosocomial pneumonia caused by multidrug-resistant (MDR) Gram-negative pathogens and the increasingly limited antibiotic treatment options are growing threats to modern medicine. As a result, older antibiotics such as polymyxins are being used as last-resort drugs for MDR nosocomial pneu-monia. Polymyxins are bactericidal against most aerobic Gram-negative bacilli. High-dose intravenous (IV) adminsitration of polymyxins, however, results in subtherapeutic concentrations at the site of infection making treatment challenging. Alternative forms of polymyxin delivery have been considered in order to better achieve the necessary concentrations at the site of infection. Several studies have evaluated the effectiveness of aerosolised polymyxins in patients with nosocomial pneumonia caused by MDR Gram -negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Here we evaluated the pharmacokinetic data supporting the use of inhaled polymyxins in nosocomial pneumonia and provide insight into the limitations and challenges that future studies should address. We have also reviewed the literature published between 2006 and 2020 on the use of aerosolised polymyx-ins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, in patients without cystic fibrosis to evaluate their safety and efficacy as monotherapy or as an adjunct to IV an-timicrobials. This review highlights the need for well-designed multicentre studies with standardised methodologies to further evaluate the effectiveness of inhaled polymyxins and to provide reliable phar-macokinetic/pharmacodynamic data in order to redefine appropriate dosing strategies. (c) 2021 Published by Elsevier Ltd.

Automated summary

This article discusses the use of polymyxins in treating MDR nosocomial pneumonia and the related pharmacokinetic data, calling for more standardized studies to evaluate its effectiveness and redefine dosing strategies.