Nichols Wright W, de Jonge Boudewijn L M, Kazmierczak Krystyna M, Karlowsky James A, Sahm Daniel F
AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA.
International Health Management Associates, Inc., Schaumburg, Illinois, USA
Antimicrob Agents Chemother. 2016 Jul 22;60(8):4743-9. doi: 10.1128/AAC.00220-16. Print 2016 Aug.
Broth microdilution antimicrobial susceptibility testing was performed for ceftazidime-avibactam and comparator agents against 7,062 clinical isolates of Pseudomonas aeruginosa collected from 2012 to 2014 in four geographic regions (Europe, Asia/South Pacific, Latin America, Middle East/Africa) as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. The majority of isolates were susceptible to ceftazidime-avibactam, with the proportions susceptible differing marginally across the four regions (MIC90, 8 to 16 μg/ml; 88.7 to 93.2% susceptible), in contrast to lower susceptibilities to the following comparator β-lactam agents: ceftazidime (MIC90, 32 to 64 μg/ml; 71.5 to 80.8% susceptible), meropenem (MIC90, >8 μg/ml; 64.9 to 77.4% susceptible), and piperacillin-tazobactam (MIC90, >128 μg/ml; 62.3 to 71.3% susceptible). Compared to the overall population, susceptibility to ceftazidime-avibactam of isolates that were nonsusceptible to ceftazidime (n = 1,627) was reduced to between 56.8% (Middle East/Africa; MIC90, 64 μg/ml) and 68.9% (Asia/South Pacific; MIC90, 128 μg/ml), but these percentages were higher than susceptibilities to other β-lactam agents (0 to 44% susceptible, depending on region and agent; meropenem MIC90, >8 μg/ml; 26.5 to 43.9% susceptible). For this subset of isolates, susceptibilities to amikacin (MIC90, >32 μg/ml; 53.2 to 80.0% susceptible) and colistin (MIC90, 1 μg/ml; 98.5 to 99.5% susceptible) were comparable to or higher than that of ceftazidime-avibactam. A similar observation was made with isolates that were nonsusceptible to meropenem (n = 1,926), with susceptibility to ceftazidime-avibactam between 67.8% (Middle East/Africa; MIC90, 64 μg/ml) and 74.2% (Europe; MIC90, 32 μg/ml) but again with reduced susceptibility to comparators except for amikacin (MIC90, >32 μg/ml; 56.8 to 78.7% susceptible) and colistin (MIC90, 1 μg/ml; 98.9 to 99.3% susceptible). Of the 8% of isolates not susceptible to ceftazidime-avibactam, the nonsusceptibility of half could be explained by their possession of genes encoding metallo-β-lactamases. The data reported here are consistent with results from other country-specific and regional surveillance studies and show that ceftazidime-avibactam demonstrates in vitro activity against globally collected clinical isolates of P. aeruginosa, including isolates that are resistant to ceftazidime and meropenem.
作为国际最佳耐药性监测网络（INFORM）全球监测项目的一部分，对2012年至2014年从四个地理区域（欧洲、亚洲/南太平洋、拉丁美洲、中东/非洲）收集的7062株铜绿假单胞菌临床分离株进行了头孢他啶-阿维巴坦及对照药物的肉汤微量稀释抗菌药敏试验。大多数分离株对头孢他啶-阿维巴坦敏感，四个区域的敏感比例略有差异（MIC90为8至16μg/ml；敏感率为88.7%至93.2%），相比之下，对以下对照β-内酰胺类药物的敏感性较低：头孢他啶（MIC90为32至64μg/ml；敏感率为71.5%至80.8%）、美罗培南（MIC90>8μg/ml；敏感率为64.9%至77.4%）和哌拉西林-他唑巴坦（MIC90>128μg/ml；敏感率为62.3%至71.3%）。与总体人群相比，对头孢他啶不敏感的分离株（n = 1627）对头孢他啶-阿维巴坦的敏感性降至56.8%（中东/非洲；MIC90为64μg/ml）至68.9%（亚洲/南太平洋；MIC90为128μg/ml）之间，但这些百分比高于对其他β-内酰胺类药物的敏感性（敏感率为0至44%，取决于区域和药物；美罗培南MIC90>8μg/ml；敏感率为26.5%至43.9%）。对于这部分分离株，对阿米卡星（MIC90>32μg/ml；敏感率为53.2%至80.0%）和黏菌素（MIC90为1μg/ml；敏感率为98.5%至99.5%）的敏感性与头孢他啶-阿维巴坦相当或更高。对美罗培南不敏感的分离株（n = 1926）也有类似的观察结果，对头孢他啶-阿维巴坦的敏感性在67.8%（中东/非洲；MIC90为64μg/ml）至74.2%（欧洲；MIC90为32μg/ml）之间，但除阿米卡星（MIC90>32μg/ml；敏感率为56.8%至78.7%）和黏菌素（MIC90为1μg/ml；敏感率为98.9%至99.3%）外，对对照药物的敏感性再次降低。在对头孢他啶-阿维巴坦不敏感的8%分离株中，一半的不敏感性可归因于其携带编码金属β-内酰胺酶的基因。此处报告的数据与其他国家和地区监测研究的结果一致，表明头孢他啶-阿维巴坦对全球收集的铜绿假单胞菌临床分离株具有体外活性，包括对头孢他啶和美罗培南耐药的分离株。
