Therapeutic options for difficult-to-treat Acinetobacter baumannii infections: a 2020 perspective

ABSTRACT

Introduction

Treatment of severe infections due to Acinetobacter baumannii with difficult-to-treat resistance (DTR-AB), which exhibits resistance to all β-lactams, β-lactam/β-lactamases inhibitor combinations, and fluoroquinolones, remains a challenge for clinicians.

Areas covered

The present perspective provides a personal view on both current and future agents for the treatment of severe DTR-AB infections.

Expert opinion

We currently are in a transition era for the treatment of DTR-AB infections, where in the past 20 years, polymyxin-based regimens have become the most used approach (although possibly suboptimal, there were few or no alternatives) and where in the next 20 years, polymyxins will likely be replaced by less toxic novel agents as first-line choices. Two novel antimicrobial agents have been recently approved that show activity against DTR-AB, cefiderocol and eravacycline, while durlobactam/sulbactam is in phase-3 of clinical development. In the near future, these agents could become important first-line choices for the treatment of DTR-AB within approved indications, or for off-label indications in the absence of dependable alternatives. Good-quality post-marketing experiences remain necessary for arising clinically relevant questions and guiding the design of further dedicated randomized controlled trials to stably optimize the use of novel agents for DTR-AB infections in the next decades.

KEYWORDS:

• Acinetobacter
• cefiderocol
• durlobactam/sulbactam
• eravacycline
• MDR
• XDR

Article highlights

• Increased case fatality up to more than 40% has been reported for infections due to DTR-AB, which exhibits resistance to all β-lactams, β-lactam/β-lactamases inhibitor combinations, and fluoroquinolones

• For most of the last decade, therapy of severe DTR-AB infections has been based on polymyxins, either polymyxin monotherapy or polymyxin-including combined regimens (although likely suboptimal, there were few or no alternatives)

• Cefiderocol and eravacycline are recently approved agents exhibiting activity against DTR-AB that in the near future could become important novel first-line choices for the treatment of DTR-AB infections within approved indications (or for off-label indications in the absence of dependable alternatives)

• Precious information from good real-life post-marketing data would allow to optimize the design of further dedicated RCT, in order to firmly guide an even more efficacious treatment of A. baumannii infections with active novel agents

This box summarizes key points contained in the article.

Declaration of interest

DR Giacobbe reports receiving honoraria from Stepstone Pharma GmbH as well as unconditional grants from Merck Sharp and Dohme Italia and Correvio Italia. M Bassetti has, meanwhile, received funding for scientific advisory boards as well as travel and speaker’s honoraria from Angelini, Astellas, AstraZeneca Basilea, Bayer, BioMerieux, Cidara, Correvio, Cubist, Menarini, Molteni, Merck Sharp and Dohme, Nabriva, Paratek, Pfizer Inc, Roche, Shionogi, Tetraphase, ThermoFisher and The Medicine Company. 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.