AUTHOR=Petropoulou Dimitra , Siopi Maria , Vourli Sophia , Pournaras Spyros 

TITLE=Activity of Sulbactam-Durlobactam and Comparators Against a National Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates From Greece

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.814530

DOI=10.3389/fcimb.2021.814530

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p><italic>Acinetobacter baumannii</italic> is a leading cause of healthcare-associated infections worldwide, due to both its persistence in the hospital setting and ability to acquire high levels of antibiotic resistance. Carbapenem-resistant <italic>A. baumannii</italic> isolates (CRAB) limit the activity of current antimicrobial regimens and new alternatives or adjuncts to traditional antibiotics are urgently needed. Durlobactam is a novel broad-spectrum inhibitor of serine-type β-lactamases that restores sulbactam (SUL) activity against <italic>A. baumannii</italic>. The sulbactam-durlobactam (SD) combination has recently completed Phase 3 testing in the global ATTACK trial.</p></sec><sec><title>Objectives</title><p>The aim of this study is to evaluate the <italic>in vitro</italic> activity of SD versus comparators against a representative nationwide collection of CRAB isolates.</p></sec><sec><title>Methods</title><p>One hundred ninety CRAB isolates were collected from clinical samples of patients hospitalized in 11 hospitals throughout Greece during 2015. <italic>In vitro</italic> activities of SD and comparators (SUL alone, amikacin, minocycline, imipenem, meropenem, colistin, SD and imipenem combined with SD) were determined by broth microdilution.</p></sec><sec><title>Results</title><p>Durlobactam restored sulbactam activity against the majority of the strains tested, with SD exhibiting the lowest MIC<sub>90</sub> (8 μg/ml) relative to the other single comparators tested; 87.9% of the isolates had SD MICs ≤4/4 µg/ml. The most active comparator was colistin (MIC<sub>90</sub> = 16 μg/ml). The addition of imipenem further lowered the MIC<sub>90</sub> of SD by one two-fold dilution.</p></sec><sec><title>Conclusions</title><p>This study demonstrated the potential utility of SD for the treatment of infections caused by <italic>A. baumannii</italic>. If its clinical efficacy is confirmed, SD may be an important therapeutic option for CRAB infections.</p></sec>