Treatment of ventilator-associated pneumonia due to carbapenem-resistant Gram-negative bacteria with novel agents: a contemporary, multidisciplinary ESGCIP perspective

ABSTRACT

Introduction

In the past 15 years, treatment of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) has represented an intricate challenge for clinicians.

Areas covered

In this perspective article, we discuss the available clinical data about novel agents for the treatment of CR-GNB VAP, together with general pharmacokinetic/pharmacodynamic principles for the treatment of VAP, in the attempt to provide some suggestions for optimizing antimicrobial therapy of CR-GNB VAP in the daily clinical practice.

Expert opinion

Recently, novel β-lactams and β-lactam/β-lactamase inhibitor combinations have become available that have shown potent in vitro activity against CR-GNB and have attracted much interest as novel, less toxic, and possibly more efficacious options for the treatment of CR-GNB VAP compared with previous standard of care. Besides randomized controlled trials, a good solution to enrich our knowledge on how to use these novel agents at best in the near future, while at the same time remaining adherent to current evidence-based guidelines, is to improve our collaboration to conduct larger multinational observational studies to collect sufficiently large populations treated in real life with those novel agents for which guidelines currently do not provide a recommendation (in favor or against) for certain causative organisms.

KEYWORDS:

• VAP
• intensive care
• cefiderocol
• ceftazidime/avibactam
• ceftolozane/tazobactam
• imipenem/relebactam
• meropenem/vaborbactam
• polymyxins
• inhaled antibiotics
• PK/PD

Article highlights

• In the past 15 years, the treatment of VAP caused by CR-GNB has represented an intricate challenge for clinicians.

• Recently, novel BL and BL/BLI combinations have become available that have shown potent in vitro activity against CR-GNB and have attracted much interest as novel, less toxic, and possibly more efficacious options for the treatment of CR-GNB VAP compared with previous standard of care.

• Besides RCTs, a good solution to enrich our knowledge on how to use these novel agents at best in the near future, while at the same time remaining adherent to current evidence-based guidelines, is to improve our collaboration to conduct larger multinational observational studies to collect sufficiently large populations treated in real life with those novel agents for which guidelines currently do not provide a recommendation (in favor or against) for certain causative organisms.

• Whether inhaled polymyxins or aminoglycosides without concomitant intravenous administration could add efficacy to intravenous treatment of CR-GNB VAP with novel BL and BL/BLI is a novel intriguing question possibly deserving dedicated investigation in forthcoming studies.

Declaration of interest

Outside the submitted work, DR Giacobbe reports investigator-initiated grants from Pfizer Inc., Gilead Italia, and Shionogi outside the submitted work, M Bassetti has received funding for research grants and/or advisor/consultant and/or speaker/chairman from Bayer, BioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Shionogi, ThermoFisher. Outside the submitted work, JF Timsit reports funding for advisory board participation from Pfizer, Merck, Gilead, Beckton-Dickinson, Medimmune, Nabriva, Paratek. Lectures: Merck, Pfizer, Shionogi, BioMérieux, and research grants for his research unit from Pfizer, Merck, and ThermoFisher. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was not funded.