Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: which is the best strategy to treat?

Introduction: Treatment of ventilator-associated pneumonia (VAP) is a major challenge. The increase in multi-drug resistant bacteria has not been accompanied by the validation of new drugs, or by any new antimicrobial strategies to exploit the available agents. VAP due to Gram-negative bacteria has increased mortality, both due to the resistant pathogens themselves and due to inappropriate treatment. Local epidemiology, patients' characteristics and clinical responses provide the most important information for therapeutic decision-making. Moreover, data on VAP therapy due to resistant bacteria are lacking, and the choice of treatment is often based on clinical practice and individual experience. Areas covered: This review summarizes the strategies available for treating the three most prevalent resistant Gram-negative organisms causing VAP: Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae. The review covers the results of a Pubmed search, clinical practice guidelines and reviews, and the authors' experience. Expert opinion: The existing evidence focuses on bloodstream infections or other sites rather than pneumonia and there are no recommendations for the treatment of VAP by multi-drug resistant Gram-negative bacteria, especially for combination regimens. The approval of new drugs is needed to provide effective and safe alternatives for treating carbapenemase-producing strains. Precision medicine and personalized approach are also fundamental in future research.