Yang Qiwen, Xu Yingchun, Jia Peiyao, Zhu Ying, Zhang Jingjia, Zhang Ge, Deng Jun, Hackel Meredith, Bradford Patricia A, Reinhart Harald
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
J Antimicrob Chemother. 2020 Jul 1;75(7):1833-1839. doi: 10.1093/jac/dkaa119.
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.
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.
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.
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).
This study demonstrated the potential utility of sulbactam/durlobactam for the treatment of infections caused by A. baumannii in China.
度洛巴坦是一种A、C和D类β-内酰胺酶的广谱抑制剂。舒巴坦是一种通用的β-内酰胺类药物，最常用于与氨苄西林联合作为β-内酰胺酶抑制剂；然而，它具有独特的性质，即对鲍曼不动杆菌具有选择性内在活性。目前，包括A类碳青霉烯酶以及C类和D类酶在内的多种β-内酰胺酶导致了广泛的耐药性。将度洛巴坦添加到舒巴坦中可恢复其对具有多种β-内酰胺酶的多重耐药鲍曼不动杆菌的体外活性。
此前，舒巴坦/度洛巴坦的药敏数据仅限于来自西方国家患者的分离株。本研究旨在确定舒巴坦/度洛巴坦对从中国大陆患者中分离出的鲍曼不动杆菌的活性。
2016 - 2018年期间，从中国大陆22个地点收集了982株近期鲍曼不动杆菌临床分离株。这些分离株来自下呼吸道、腹腔内、泌尿道以及皮肤和皮肤结构感染。通过肉汤微量稀释法测定舒巴坦/度洛巴坦及对照药物的体外活性。
添加度洛巴坦恢复了舒巴坦对大多数测试菌株的活性。舒巴坦/度洛巴坦对所有鲍曼不动杆菌的MIC90为2mg/L，而单独舒巴坦的MIC90为64mg/L。对于831株耐碳青霉烯类分离株，舒巴坦/度洛巴坦的MIC90为2mg/L保持不变。黏菌素是唯一具有可比活性的对照药物（MIC90 = 1mg/L）。
本研究证明了舒巴坦/度洛巴坦在中国治疗鲍曼不动杆菌感染的潜在效用。
