NXL104（阿维巴坦）联合β-内酰胺类药物对包括产 OXA-48 碳青霉烯酶肺炎克雷伯菌在内的革兰氏阴性菌的体外活性。
In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae.
机构信息
Department of Clinical Microbiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
出版信息
Int J Antimicrob Agents. 2012 Jan;39(1):86-9. doi: 10.1016/j.ijantimicag.2011.09.012. Epub 2011 Oct 29.
The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 β-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.
本研究旨在探讨氨曲南（前称 NXL104）与亚胺培南、头孢吡肟或头孢他啶联合应用对革兰氏阴性菌的体外抗菌活性。细菌分离株包括：携带 PER-1 型β-内酰胺酶的铜绿假单胞菌（n=14）；携带 PER-1、OXA-51 和 OXA-58 的鲍曼不动杆菌（n=20）；耐碳青霉烯类肺炎克雷伯菌（n=25）和携带 OXA-48 的大肠埃希菌（n=1）；携带 IMP-1 型金属β-内酰胺酶和超广谱β-内酰胺酶（ESBL）的同时耐碳青霉烯类大肠埃希菌（n=1）；耐碳青霉烯类黏质沙雷菌（n=1）；以及耐碳青霉烯类大肠埃希菌（n=20）和肺炎克雷伯菌分离株（n=12），这些分离株均携带 CTX-M-15 ESBL。采用临床和实验室标准协会（CLSI）方法，在 Mueller-Hinton 琼脂上，通过测定 4mg/L 氨曲南与亚胺培南、头孢吡肟和头孢他啶联合使用时的最低抑菌浓度（MIC）。亚胺培南/氨曲南和头孢他啶/氨曲南对鲍曼不动杆菌分离株的活性有限，而头孢吡肟/氨曲南和头孢他啶/氨曲南对铜绿假单胞菌具有活性。携带 OXA-48 型β-内酰胺酶的肺炎克雷伯菌对亚胺培南耐药（MIC90 对 90%的细菌（MIC90）≥4mg/L）。氨曲南 4mg/L 与亚胺培南、头孢吡肟和头孢他啶联合使用的 MIC90 值对所有菌株均处于敏感范围（MIC90≤0.5mg/L）。所有携带 CTX-M-15 型β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌分离株对氨曲南联合用药的抑制浓度均≤1mg/L，且根据 CLSI 折点标准，所有这些分离株对亚胺培南、头孢吡肟和头孢他啶均 100%敏感。综上所述，亚胺培南、头孢吡肟和头孢他啶与氨曲南联合应用可能为治疗携带 OXA-48 酶的肺炎克雷伯菌以及携带 CTX-M-15 酶的肺炎克雷伯菌和大肠埃希菌感染提供一种有前景的治疗策略。
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