Qiwen Yang1, Yingchun Xu1, Peiyao Jia1,2, Ying Zhu1, Jingjia Zhang1, Ge Zhang1, Jun Deng3, Meredith Hackel4, Patricia A Bradford5, Harald Reinhart3. 1. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 2. Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 3. Zai Lab (Shanghai) Co., Ltd, Pudong, Shanghai, China. 4. IHMA, Schaumburg, IL, USA. 5. Antimicrobial Development Specialists, LLC, Nyack, NY, USA.
Abstract
BACKGROUND: Durlobactam is a broad-spectrum inhibitor of class A, C and D β-lactamases. Sulbactam is a generic β-lactam most commonly used as a β-lactamase inhibitor in combination with ampicillin; however, it has a unique property in that it has selective intrinsic activity against Acinetobacter baumannii. Currently, there is widespread resistance caused by multiple β-lactamases including class A carbapenemases and class C and class D enzymes. The addition of durlobactam to sulbactam restores in vitro activity against MDR A. baumannii that possess multiple β-lactamases. OBJECTIVES: Previously, susceptibility data for sulbactam/durlobactam were limited to isolates from patients in Western countries. This study was undertaken to determine the activity of sulbactam/durlobactam against A. baumannii isolated from patients in mainland China. METHODS: Nine hundred and eighty-two recent A. baumannii clinical isolates were collected from 22 sites across mainland China during 2016-18. The isolates were collected from lower respiratory tract, intra-abdominal, urinary tract and skin and skin structure infections. The in vitro activities of sulbactam/durlobactam and comparators were determined by broth microdilution. RESULTS: The addition of durlobactam restored the activity of sulbactam against the majority of the strains tested. The MIC90 of sulbactam/durlobactam was 2 mg/L for all A. baumannii, compared with 64 mg/L for sulbactam alone. The MIC90 of sulbactam/durlobactam of 2 mg/L remained unchanged for 831 carbapenem-resistant isolates. Colistin was the only comparator with comparable activity (MIC90 = 1 mg/L). CONCLUSIONS: This study demonstrated the potential utility of sulbactam/durlobactam for the treatment of infections caused by A. baumannii in China.
BACKGROUND:Durlobactam is a broad-spectrum inhibitor of class A, C and D β-lactamases. Sulbactam is a generic β-lactam most commonly used as a β-lactamase inhibitor in combination with ampicillin; however, it has a unique property in that it has selective intrinsic activity against Acinetobacter baumannii. Currently, there is widespread resistance caused by multiple β-lactamases including class A carbapenemases and class C and class D enzymes. The addition of durlobactam to sulbactam restores in vitro activity against MDR A. baumannii that possess multiple β-lactamases. OBJECTIVES: Previously, susceptibility data for sulbactam/durlobactam were limited to isolates from patients in Western countries. This study was undertaken to determine the activity of sulbactam/durlobactam against A. baumannii isolated from patients in mainland China. METHODS: Nine hundred and eighty-two recent A. baumannii clinical isolates were collected from 22 sites across mainland China during 2016-18. The isolates were collected from lower respiratory tract, intra-abdominal, urinary tract and skin and skin structure infections. The in vitro activities of sulbactam/durlobactam and comparators were determined by broth microdilution. RESULTS: The addition of durlobactam restored the activity of sulbactam against the majority of the strains tested. The MIC90 of sulbactam/durlobactam was 2 mg/L for all A. baumannii, compared with 64 mg/L for sulbactam alone. The MIC90 of sulbactam/durlobactam of 2 mg/L remained unchanged for 831 carbapenem-resistant isolates. Colistin was the only comparator with comparable activity (MIC90 = 1 mg/L). CONCLUSIONS: This study demonstrated the potential utility of sulbactam/durlobactam for the treatment of infections caused by A. baumannii in China.
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