Ava J Dorazio, Ellen G Kline, Kevin M Squires, Marissa P Griffith, Yohei Doi, Ryan K Shields
{"title":"Comparative <i>in vitro</i> activity of sulbactam with avibactam or durlobactam against carbapenem-resistant <i>Acinetobacter baumannii</i>.","authors":"Ava J Dorazio, Ellen G Kline, Kevin M Squires, Marissa P Griffith, Yohei Doi, Ryan K Shields","doi":"10.1093/jacamr/dlaf098","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To determine the <i>in vitro</i> activity of sulbactam in combination with avibactam or durlobactam with and without meropenem or imipenem against carbapenem-resistant <i>Acinetobacter baumannii</i> clinical isolates.</p><p><strong>Methods: </strong>Standardized susceptibility testing by broth microdilution was performed to determine MICs for imipenem, meropenem and sulbactam alone, and for combinations including sulbactam/avibactam, sulbactam/durlobactam, sulbactam/avibactam/meropenem, sulbactam/avibactam/imipenem, sulbactam/durlobactacm/meropenem and sulbactam/durlobactam/imipenem. Whole-genome sequencing was also performed to compare MICs to key resistance determinants, including mutations in penicillin-binding proteins (PBPs).</p><p><strong>Results: </strong>Median sulbactam/durlobactam and sulbactam/avibactam MICs were 2 and 16 mg/L, respectively. Imipenem potentiated the <i>in vitro</i> activity of both combinations to a greater extent than meropenem corresponding to median sulbactam/durlobactam/imipenem and sulbactam/avibactam/imipenem MICs of 1 and 8 mg/L, respectively. Carbapenem combinations were more active than combinations without a carbapenem against isolates with PBP3 mutations.</p><p><strong>Conclusions: </strong>These data show that imipenem potentiates sulbactam-based combinations to a greater extent than meropenem; however, future studies are needed to define how these data should be applied in clinical practice.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf098"},"PeriodicalIF":3.3000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205954/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlaf098","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: To determine the in vitro activity of sulbactam in combination with avibactam or durlobactam with and without meropenem or imipenem against carbapenem-resistant Acinetobacter baumannii clinical isolates.
Methods: Standardized susceptibility testing by broth microdilution was performed to determine MICs for imipenem, meropenem and sulbactam alone, and for combinations including sulbactam/avibactam, sulbactam/durlobactam, sulbactam/avibactam/meropenem, sulbactam/avibactam/imipenem, sulbactam/durlobactacm/meropenem and sulbactam/durlobactam/imipenem. Whole-genome sequencing was also performed to compare MICs to key resistance determinants, including mutations in penicillin-binding proteins (PBPs).
Results: Median sulbactam/durlobactam and sulbactam/avibactam MICs were 2 and 16 mg/L, respectively. Imipenem potentiated the in vitro activity of both combinations to a greater extent than meropenem corresponding to median sulbactam/durlobactam/imipenem and sulbactam/avibactam/imipenem MICs of 1 and 8 mg/L, respectively. Carbapenem combinations were more active than combinations without a carbapenem against isolates with PBP3 mutations.
Conclusions: These data show that imipenem potentiates sulbactam-based combinations to a greater extent than meropenem; however, future studies are needed to define how these data should be applied in clinical practice.