Journal
PHARMACOTHERAPY
Volume 41, Issue 9, Pages 762-780Publisher
WILEY
DOI: 10.1002/phar.2607
Keywords
Acinetobacter baumannii; multidrug resistance; pharmacodynamics; pharmacokinetics
Categories
Funding
- Entasis
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Treatment of patients with carbapenem-resistant Acinetobacter baumannii infections remains challenging, with limited viable treatment options and significant risk of nephrotoxicity associated with polymyxin therapy. New agents with clinically relevant activity against CRAB isolates and favorable toxicity profiles are urgently needed to address this urgent threat pathogen.
This review critically appraises the published microbiologic and clinical data on the treatment of patients with carbapenem-resistant Acinetobacter baumannii infections. Despite being recognized as an urgent threat pathogen by the CDC and WHO, optimal treatment of patients with serious CRAB infections remains ill-defined. Few commercially available agents exhibit reliable in vitro activity against CRAB. Historically, polymyxins have been the most active agents in vitro, though interpretations of susceptibility data are difficult given issues surrounding MIC testing methodologies and lack of correlation between MICs and clinical outcomes. Most available preclinical and clinical data involve use of polymyxins, tetracyclines, and sulbactam, alone and in combination. As the number of viable treatment options is limited, combination therapy with a polymyxin is often used for patients with CRAB infections, despite the significant risk of nephrotoxicity. However, no treatment regimen has been found to reduce mortality, which exceeds 40% across most studies, or substantially improve clinical response. While some newer agents, such as eravacycline and cefiderocol, have demonstrated in vitro activity, clinical efficacy has not been fully established. New agents with clinically relevant activity against CRAB isolates and favorable toxicity profiles are sorely needed.
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