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舒巴坦/米诺环素联合应用增强了对产双重碳青霉烯酶鲍曼不动杆菌的杀菌作用。

Enhanced bacterial killing with a combination of sulbactam/minocycline against dual carbapenemase-producing Acinetobacter baumannii.

机构信息

Department of Clinical Microbiology, Christian Medical College, Vellore, 632004, India.

Department of Orthopedics, Christian Medical College, Vellore, India.

出版信息

Eur J Clin Microbiol Infect Dis. 2023 May;42(5):645-651. doi: 10.1007/s10096-023-04583-z. Epub 2023 Mar 11.

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is often difficult to treat. Considering the current circumstances, there is an unquestionable need for new therapeutic options to treat CRAB infections. In the present study, the synergistic activity of sulbactam-based combination was determined against genetically characterized CRAB isolates. Non-duplicate CRAB isolates (n = 150) recovered from blood culture and endotracheal aspirates were included in this study. The minimum inhibitory concentrations (MICs) of tetracyclines (minocycline, tigecycline, eravacycline) and their comparators (meropenem, sulbactam, cefoperazone/sulbactam, ceftazidime/avibactam, and colistin) were determined using the microbroth dilution method. Six isolates were tested for the synergistic activity of various sulbactam-based combinations using time-kill experiments. Tigecycline and minocycline showed a wide spread of MICs with most isolates in the range of 1 to 16 mg/L. The MIC of eravacycline (0.5 mg/L) was four dilutions lower than that of tigecycline (8 mg/L). Minocycline with sulbactam was the most active dual combination against OXA-23 like (n = 2) and NDM with OXA-23 like producers (n = 1), which resulted in ≥ 2 log kill. The combination of ceftazidime-avibactam with sulbactam showed ≥ 3 log kill against all the three tested OXA-23 like producing CRAB isolates, but showed no activity against dual carbapenemase producers. Sulbactam with meropenem showed ≥ 2 log kill against one OXA-23 like producing CRAB isolate. The findings suggest that sulbactam-based combination may confer therapeutic benefits against CRAB infections.

摘要

耐碳青霉烯鲍曼不动杆菌(CRAB)通常难以治疗。考虑到目前的情况,毫无疑问需要新的治疗选择来治疗 CRAB 感染。在本研究中,测定了基于舒巴坦的联合用药对基因特征明确的 CRAB 分离株的协同活性。本研究纳入了从血培养和气管抽吸物中分离的非重复 CRAB 分离株(n=150)。使用微量肉汤稀释法测定四环素(米诺环素、替加环素、依拉环素)及其对照药物(美罗培南、舒巴坦、头孢哌酮/舒巴坦、头孢他啶/阿维巴坦和多粘菌素)的最低抑菌浓度(MIC)。使用时间杀伤实验测试了 6 株分离株对各种基于舒巴坦的联合用药的协同活性。替加环素和米诺环素的 MIC 分布广泛,大多数分离株的范围为 1 至 16mg/L。依拉环素(0.5mg/L)的 MIC 比替加环素(8mg/L)低四个稀释度。米诺环素与舒巴坦联合使用对 OXA-23 样(n=2)和同时携带 OXA-23 样和 NDM 的产酶株(n=1)最为有效,可导致 2 对数杀灭。头孢他啶-阿维巴坦与舒巴坦联合使用对三种测试的 OXA-23 样产酶 CRAB 分离株均显示 3 对数杀灭,但对双重碳青霉烯酶产酶株无活性。舒巴坦与美罗培南联合使用对一株 OXA-23 样产酶 CRAB 分离株显示 2 对数杀灭。研究结果表明,基于舒巴坦的联合用药可能对 CRAB 感染具有治疗益处。

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