Sulbactam-Durlobactam for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections

Background: Antimicrobial resistance (AMR) is a major health crisis specifically associated with Acinetobacter. Among different Acinetobacter species, Acinetobacter baumannii is known as the greatest culprit concerning clinical significance. Of most importance, carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB) infections are the fourth leading global cause of death attributable to AMR. Consequently, CRAB has been established globally as a top priority pathogen for the development of novel antimicrobials. Sulbactam--durlobactam received Food and Drug Administration (FDA) approval to target this resistant microorganism. Mechanism of Action, Pharmacodynamics, and Pharmacokinetics: This innovative combination uses sulbactam, which is a first-generation beta-lactamase inhibitor with antibacterial activity against Acinetobacter spp. Considering sulbactam is susceptible to cleavage by numerous beta-lactamases, the benefit of this coformulated product is the addition of durlobactam. Durlobactam is a new member of the diazabicyclooctane class of beta-lactamase inhibitors with broad spectrum activity against several serine beta-lactamases, making it able to restore the sulbactam's activity against the exclusively multidrug-resistant strains. Overall, the pharmacokinetic and pharmacodynamic parameter for sulbactam is time above minimum inhibitory concentration (T >MIC) and for durlobactam is 24-hour unbound area under the curve. The estimated half-life for sulbactam-durlobactam is approximately 2 hours. Clinical Trials: The ATTACK, a phase 3 trial, used sulbactam-durlobactam in patients with laboratory-confirmed CRAB. The primary efficacy end point was 28-day all-cause mortality. The combination was noninferior to colistin. The drug was well tolerated and effective in reducing mortality from serious infections caused by CRAB, along with multidrug-resistant strains. The sulbactam-durlobactam group had significantly lower incidence of nephrotoxicity. Therapeutic Advance: Sulbactam-durlobactam is an unconventional dual beta-lactamase inhibitor coformulated product. It holds activity against CRAB infections noninferior to other agents, yet with fewer kidney side effects. This novel product deserves to be regarded as an important agent added to the current battlefield landscape against multiple resistant organisms encountered in current medical practice.