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

Acinetobacter baumannii-calcoaceticus complex isolates commonly cause of nosocomial infections. This organism displays clonal dissemination and is able to accumulate resistance traits by horizontal gene transfer, natural transformation, acquisition of mutations, and mobilization of genetic elements that modulate gene expression. 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 beta-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.

Automated summary

Acinetobacter baumannii-calcoaceticus complex is a common cause of nosocomial infections with high antibiotic resistance. Traditional combination therapy includes colistin, sulbactam, and tetracyclines. New beta-lactam agents like cefiderocol and sulbactam-durlobactam have shown contrasting results in recent clinical trials. Effective treatment for CRAB infections requires a personalized approach considering host factors, site of infection, pharmacokinetic-pharmacodynamic principles, and local molecular epidemiology.