New treatments of multidrug-resistant Gram-negative ventilatorassociated pneumonia

Ventilator-associated pneumonia (VAP) remains an important clinical problem globally, being associated with significant morbidity and mortality. As management of VAP requires adequate and timely antibiotic administration, global emergence of antimicrobial resistance poses serious challenges over our ability to maintain this axiom. Development of antimicrobials against MDR Gram-negative pathogens has therefore emerged as a priority and some new antibiotics have been marketed or approach late stage of development. The aim of this review is to analyse new therapeutic options from the point view of potential treatment of VAP. Among recently developed antimicrobials presented herein, it is obvious that we will have promising therapeutic options against VAP caused by Enterobacteriaceae excluding those producing metallo-β-lactamases, against which only cefiderocol and aztreonam/avibactam are expected to be active. Against infections caused by carbapenem non-susceptible Pseudomonas aeruginosa, ceftolozane/tazobactam and to a lesser extend ceftazidime/avibactam may cover a proportion of current medical needs, but there still remain a considerable proportion of strains which harbor other resistance mechanisms. Murepavadin and cefiderocol hold promise against this particularly notorious pathogen. Finally, Acinetobacter baummannii remains a treatment-challenge. Eravacycline, cefiderocol and probably plazomicin seem to be the most promising agents against this difficult-to treat pathogen, but we have still a long road ahead, to see their position in clinical practice and particularly in VAP. In summary, despite persisting and increasing unmet medical needs, several newly approved and forthcoming agents hold promise for the treatment of VAP and hopefully will enrich our antimicrobial arsenal in the next few years. Targeted pharmacokinetic and clinical studies in real-life scenario of VAP are important to position these new agents in clinical practice, whereas vigilant use will ensure their longevity in our armamentarium.