IHMA, Inc., Schaumburg, Illinois, USA.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0078122. doi: 10.1128/aac.00781-22. Epub 2022 Aug 25.
Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination designed to treat serious Acinetobacter baumannii complex (ABC) infections, including carbapenem-non-susceptible and multidrug-resistant (MDR) isolates. The current study characterized the activity of sulbactam-durlobactam against a collection of 5,032 ABC clinical isolates collected in 33 countries across the Asia/South Pacific region, Europe, Latin America, the Middle East, and North America from 2016 to 2021. The sulbactam-durlobactam MIC and MIC were 1 and 2 μg/mL, respectively, for all ABC isolates tested. The addition of durlobactam (at a fixed concentration of 4 μg/mL) to sulbactam decreased its MIC by 8-fold (from 8 to 1 μg/mL) and its MIC by 32-fold (from 64 to 2 μg/mL) for all ABC isolates. The activity of sulbactam-durlobactam was maintained across individual ABC species, years, global regions of collection, specimen sources, and resistance phenotypes, including MDR and extensively drug-resistant (XDR) isolates. At 4 μg/mL (preliminary sulbactam-durlobactam susceptible MIC breakpoint), sulbactam-durlobactam inhibited 98.3% of all ABC isolates and >96% of sulbactam-, imipenem-, ciprofloxacin-, amikacin-, and minocycline-non-susceptible isolates; as well as colistin-resistant, MDR, and XDR isolates. Most imipenem-non-susceptible ABC isolates (96.8%, 2,488/2,570) were carbapenem-resistant A. baumannii (CRAB); 96.9% (2,410/2,488) of CRAB isolates were sulbactam-durlobactam-susceptible. More than 80% of ABC isolates had sulbactam-durlobactam MIC values that were ≥2 doubling-dilutions (4-fold) lower than sulbactam alone. Only 1.7% (84/5,032) of ABC isolates from 2016 to 2021 had sulbactam-durlobactam MIC values of >4 μg/mL. Of the 84 isolates, 94.0% were A. baumannii, 4.8% were A. pittii, and 1.2% were A. nosocomialis. In summary, sulbactam-durlobactam demonstrated potent antibacterial activity against a 2016 to 2021 collection of geographically diverse clinical isolates of ABC isolates, including carbapenem-non-susceptible and MDR isolates.
舒巴坦-多利布坦是一种β-内酰胺-内酰胺酶抑制剂组合,旨在治疗严重的鲍曼不动杆菌复合(ABC)感染,包括对碳青霉烯类药物不敏感和多重耐药(MDR)的分离株。本研究对 2016 年至 2021 年期间在亚洲/太平洋地区、欧洲、拉丁美洲、中东和北美 33 个国家/地区收集的 5032 株 ABC 临床分离株进行了舒巴坦-多利布坦的活性特征分析。舒巴坦-多利布坦对所有 ABC 分离株的 MIC 和 MIC 分别为 1 和 2μg/mL。多利布坦(固定浓度为 4μg/mL)的加入使舒巴坦的 MIC 降低了 8 倍(从 8 到 1μg/mL),MIC 降低了 32 倍(从 64 到 2μg/mL),对所有 ABC 分离株均有效。舒巴坦-多利布坦的活性在各个 ABC 种、年份、全球采集区域、标本来源和耐药表型(包括 MDR 和广泛耐药(XDR)分离株)中均得到维持。在 4μg/mL(初步舒巴坦-多利布坦敏感 MIC 折点)时,舒巴坦-多利布坦抑制了所有 ABC 分离株的 98.3%,以及 96%以上的舒巴坦、亚胺培南、环丙沙星、阿米卡星和米诺环素耐药分离株;以及粘菌素耐药、MDR 和 XDR 分离株。大多数对亚胺培南不敏感的 ABC 分离株(96.8%,2488/2570)为碳青霉烯类药物耐药鲍曼不动杆菌(CRAB);2410/2488 株 CRAB 分离株对舒巴坦-多利布坦敏感。超过 80%的 ABC 分离株的舒巴坦-多利布坦 MIC 值比单独使用舒巴坦低 2 倍(4 倍)。在 2016 年至 2021 年期间,只有 1.7%(84/5032)的 ABC 分离株的舒巴坦-多利布坦 MIC 值>4μg/mL。在 84 株分离株中,94.0%为鲍曼不动杆菌,4.8%为鲍氏不动杆菌,1.2%为医院不动杆菌。总之,舒巴坦-多利布坦对 2016 年至 2021 年期间地理分布广泛的 ABC 临床分离株的集合具有很强的抗菌活性,包括对碳青霉烯类药物不敏感和 MDR 分离株。