Multidrug Resistant Acinetobacter baumannii: Resistance by Any Other Name Would Still be Hard to Treat

Purpose of Review Acinetobacter baumannii (AB) is an infamous nosocomial pathogen with a seemingly limitless capacity for antimicrobial resistance, leading to few treatment options and poor clinical outcomes. The debatably low pathogenicity and virulence of AB are juxtaposed by its exceptionally high rate of infection-related mortality, likely due to delays in time to effective antimicrobial therapy secondary to its predilection for resistance to first-line agents. Recent studies of AB and its infections have led to a burgeoning understanding of this critical microbial threat and provided clinicians with new ammunition for which to target this elusive pathogen. This review will provide an update on the virulence, resistance, diagnosis, and treatment of multidrug resistant (MDR) AB. Recent Findings Advances in bacterial genomics have led to a deeper understanding of the unique mechanisms of resistance often present in MDR AB and how they may be exploited by new antimicrobials or optimized combinations of existing agents. Further, improvements in rapid diagnostic tests (RDTs) and their more pervasive use in combination with antimicrobial stewardship interventions have allowed for more rapid diagnosis of AB and decreases in time to effective therapy. Unfortunately, there remains a paucity of high-quality clinical data for which to inform the optimal treatment of MDR AB infections. In fact, recently completed studies have failed to identify a combination regimen that is consistently superior to monotherapy, despite the benefits demonstrated in vitro. Encouragingly, new and updated guidelines offer strategies for the treatment of MDR AB and may help to harmonize the use of high toxicity agents such as the polymyxins. Finally, new antimicrobial agents such as eravacycline and cefiderocol have promising in vitro activity against MDR AB but their place in therapy for these infections remains to be determined. Notwithstanding available clinical trial data, polymyxin-based combination therapies with either a carbapenem, minocycline, or eravacycline remain the treatment of choice for MDR, particularly carbapenem-resistant, AB. Incorporating antimicrobial stewardship intervention with RDTs relevant to MDR AB can help avoid potentially toxic combination therapies and catalyze the most important modifiable risk factor for mortality-time to effective therapy. Further research efforts into pharmacokinetic/pharmacodynamic-based dose optimization and clinical outcomes data for MDR AB continue to be desperately needed.