1073. Sulbactam-Durlobactam Has Potent Activity Against Multidrug-Resistant Acinetobacter baumannii Clinical Isolates From Thai Patients With Chronic Infections
Year: 2021
Type: article
Abstract: Background Due to the increase in multi-drug resistance (MDR) of Acinetobacter baumannii chronic infections with accompanying considerable morbidity and mortality, it is imperative to find effective novel treatments. Durlobactam (DUR) is a potent broad-spectrum inhibitor of Ambler classes A, C and D serine β-lactamases that effectively restores sulbactam (SUL) activity against MDR A.baumannii isolates. SUL-DUR is currently in late-stage development for the treatment of infections caused by Acinetobacter spp., including drug resistant isolates. In this study, we sought to evaluate potency of SUL-DUR against MDR A. baumannii isolates collected from Thai patients with chronic infections. Methods Non-duplicative clinical strains were isolated during 2016–2019 from 200 chronically infected patients in different medical wards with a variety of different infections at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Susceptibility testing of SUL-DUR and comparator agents was performed according to CLSI guidelines. SUL-DUR was also tested on a background of imipenem (IPM) therapy (SUL-IPM titrated at a 1:1 ratio plus DUR fixed at 4 mg/L). Data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 92% sulbactam-resistant (using a breakpoint of 4 mg/L), 91% carbapenem-resistant, 74% amikacin resistant and 8% colistin resistant. In contrast, the SUL-DUR MIC90 was 4 mg/L compared with 64 mg/L for sulbactam alone. SUL-DUR was equally potent across antibiotic-resistant subsets. Only 6 isolates (3%) had SUL-DUR MIC values >4 mg/L. Interestingly, addition of imipenem to SUL-DUR showed similar potency as SUL-DUR alone, with an MIC90 of 2 mg/L. Conclusion SUL-DUR showed potent in vitro activity against contemporary clinical isolates from a hospital in Bangkok, Thailand. If successfully developed, SUL-DUR may be an important new therapeutic option for the treatment of MDR Acinetobacter infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee)
Source: Open Forum Infectious Diseases
Institutions: Thai Red Cross Society, Chulalongkorn University, King Chulalongkorn Memorial Hospital, University of Cologne, QIMR Berghofer Medical Research Institute, Yamagata Prefectural Central Hospital, Mae Fah Luang University, Mae Fah Luang University Hospital, Mae Fah Luang University Hospital, Chiang Rai, Mahidol University, The Kids Research Institute Australia, The University of Western Australia, Entasis Therapeutics (United States)
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,465
OpenAlex ID: W4200627772