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Review
. 2023 May 1;76(Suppl 2):S179-S193.
doi: 10.1093/cid/ciad094.

Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections

Ryan K Shields  1 , David L Paterson  2 , Pranita D Tamma  3
Affiliations
Review

Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections

Ryan K Shields et al. Clin Infect Dis. .

Abstract

Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) is one of the top-priority pathogens for new antibiotic development. Unlike other antibiotic-resistant threats, none of the available therapies have been shown to consistently reduce mortality or improve patient outcomes in clinical trials. Antibiotic combination therapy is routinely used in clinical practice; however, the preferred combination has not been defined. This narrative review focuses on evidence-based solutions for the treatment of invasive CRAB infections. We dissect the promise and perils of traditional agents used in combination, such as colistin, sulbactam, and the tetracyclines, and offer clinical pearls based on our interpretation of the available data. Next, we investigate the merits of newly developed β-lactam agents like cefiderocol and sulbactam-durlobactam, which have demonstrated contrasting results in recent randomized clinical trials. The review concludes with the authors' perspective on the evolving treatment landscape for CRAB infections, which is complicated by limited clinical data, imperfect treatment options, and a need for future clinical trials. We propose that effective treatment for CRAB infections requires a personalized approach that incorporates host factors, the site of infection, pharmacokinetic-pharmacodynamic principles, local molecular epidemiology of CRAB isolates, and careful interpretation of antibiotic susceptibility testing results. In most clinical scenarios, a dose-optimized, sulbactam-based regimen is recommended with the addition of at least one other in vitro active agent. Should sulbactam-durlobactam receive regulatory approval, recommendations will need to be re-evaluated with the most recent evidence.

Keywords: Acinetobacter; cefiderocol; colistin; durlobactam; sulbactam.

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Conflict of interest statement

Potential conflicts of interest . R. K. S. has served as a consultant for Allergan, Cidara, Entasis, GlaxoSmithKline, Melinta, Menarini, Merck, Pifzer, Shionogi, Utility, and Venatorx, and has received investigator-initiated funding from Merck, Melinta, Roche, Shionogi, and Venatorx. D. L. P. has served as a consultant for Accelerate, Biomerieux, Entasis, Lysovant, Merck, Pfizer, Shionogi, and Venatorx, and has received research grants from Merck, Pfizer, and Shionogi. P. D. T. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
A brief timeline of noteworthy CRAB clinical trials. *Full results have not yet been published. Abbreviations: CR, carbapenem-resistant; CRAB, carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex; MDR, multidrug-resistant; SUL-DUR, sulbactam-durlobactam; VAP, ventilator-associated pneumonia; XDR, extensively drug-resistant.
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