Navigating Available Treatment Options for Carbapenem-ResistantAcinetobacter baumannii-calcoaceticusComplex Infections

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.

A novel antibiotic class targeting the lipopolysaccharide transporter

“…Increasingly, the emergence of pan-drug-resistant A. baumannii has been documented 8 , 9 . Recent approvals of the siderophore-conjugated β-lactam cefiderocol and β-lactamase inhibitor durlobactam in combination with sulbactam offer new treatment options for infections caused by ABC 10 , 11 . However, older or repurposed agents (such as the polymyxin class) with unfavourable safety and efficacy profiles continue to define the standard of care 12 – 14 .…”

Candent issues in pneumonia. Reflections from the Fifth Annual Meeting of Spanish Experts 2023

“…A. baumannii is associated with resistance mechanisms that the World Health Organization (WHO) introduced in the “ WHO priority list for research and development of new antibiotics for antibiotic-resistant bacteria” (Priority 1: critical) [ 176 ]. Especially in HAP-VAP infections, combinations of ampicillin-sulbactam together with cefiderocol, tigecycline or colistin have been proposed to increase the probability of therapeutic success [ 177 ]. IDSA and ESCMID recommendations in high-risk and severe ill patients suggest the combination of at least of two antibiotics with in vitro activity.…”

“…IDSA and ESCMID recommendations in high-risk and severe ill patients suggest the combination of at least of two antibiotics with in vitro activity. Table 10 shows the differences between the recommendations for treatment of A. baumannii Carbapenems Resistant (CR) provided by IDSA and ESCMID [ 163 , 177 , 178 ]. Among the future options, it is worth highlighting the trials that are being carried out with sulbactam/durlobactam.…”

Current treatment options for pneumonia caused by carbapenem-resistant Acinetobacter baumannii

“…In the largest observational study examining its efficacy for MDR-AB infections, 55 patients, 58% of whom had a respiratory infection, received either minocycline monotherapy ( n = 3) or minocycline in combination with additional antimicrobials ( n = 52) with 73% of these patients achieving clinical success [40]. Interpretation of this retrospective, single-center study is complicated by the diversity of antibiotics used in combination therapy and the conservative 100 mg dose of minocycline administered [41]. In fact, in vitro pharmacodynamic modeling supports high dose minocycline at doses of 350 mg daily [17]; though safety and efficacy of this approach has yet to be borne out in clinical trials.…”