Recent advances in the pharmacological management of infections due to multidrug-resistant Gram-negative bacteria

ABSTRACT

Introduction: The emergence and diffusion of multidrug-resistant Gram-negative bacteria (MDR-GNB) is an unprecedented threat, with prevalences as high as 10–50% being reported in many countries.

Areas covered: In the present review, we discuss the management of infections due to MDR-GNB, focusing in particular on current strategies and novel agents with already available results from phase 3 randomized controlled trials.

Expert commentary: Some new drugs, such as ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam, which have become available in the past months, have increased our chance of improving survival in severe carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae infections; while others, with potent activity against carbapenem-resistant Acinetobacter baumannii which is currently the highest priority regarding the need for novel agents, will become available in the near future. In the meantime, the focus of both clinical practice and research is slowly but steadily widening from efficacy and tolerability of new treatment options to also future preservation of their antimicrobial activity. This is reflected in clinical practice by more attention paid to antimicrobial stewardship initiatives, and in clinical research by growing interest in exploring resistance development as a major endpoint in both preclinical and clinical studies.

KEYWORDS:

• Antimicrobial resistance
• Klebsiella
• Enterobacteriaceae
• Pseudomonas
• Acinetobacter
• carbapenemases

Declaration of interest

D Giacobbe reports personal fees from Stepstone Pharma GmbH and an unconditioned grant from MSD Italia outside the submitted work. M Mikulska received an investigational grant and non-financial support from Gilead, as well as personal fees from Gilead, MSD, Jansen, Pfizer, Astellas and Biotest outside the submitted work. C Viscoli reports personal fees from MSD Int., Gilead, Forrest Italia, Angelini and Pfizer outside the submitted work. 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

The manuscript was not funded.