Sader Helio S, Castanheira Mariana, Flamm Robert K, Farrell David J, Jones Ronald N
JMI Laboratories, North Liberty, Iowa, USA.
Antimicrob Agents Chemother. 2014;58(3):1684-92. doi: 10.1128/AAC.02429-13. Epub 2013 Dec 30.
The activities of the novel β-lactam-β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli-8,640 Enterobacteriaceae, 1,967 Pseudomonas aeruginosa, and 321 Acinetobacter sp. isolates-were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% of Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotype Escherichia coli and Klebsiella pneumoniae, meropenem-nonsusceptible (MIC≥2 μg/ml) K. pneumoniae, and ceftazidime-nonsusceptible Enterobacter cloacae. Among ESBL-phenotype K. pneumoniae strains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Among P. aeruginosa strains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptible P. aeruginosa (MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml). Acinetobacter spp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such as K. pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and meropenem-nonsusceptible P. aeruginosa.
对新型β-内酰胺-β-内酰胺酶抑制剂组合头孢他啶-阿维巴坦及对照药物针对一组当代具有临床意义的革兰氏阴性杆菌的活性进行了评估。阿维巴坦是一种新型非β-内酰胺类β-内酰胺酶抑制剂，可抑制安布勒A类、C类和一些D类酶。总共从73家美国医院收集了10928株革兰氏阴性杆菌，其中8640株肠杆菌科细菌、1967株铜绿假单胞菌和321株不动杆菌属菌株，并在美国爱荷华州北自由市的中央监测实验室（JMI实验室）通过参考肉汤微量稀释法检测其敏感性。头孢他啶与阿维巴坦以4μg/ml的固定浓度联合使用。总体而言，头孢他啶-阿维巴坦MIC≤4μg/ml时，99.8%的肠杆菌科菌株被抑制。头孢他啶-阿维巴坦对产超广谱β-内酰胺酶（ESBL）表型的大肠埃希菌和肺炎克雷伯菌、美罗培南不敏感（MIC≥2μg/ml）的肺炎克雷伯菌以及头孢他啶不敏感的阴沟肠杆菌具有活性。在产ESBL表型的肺炎克雷伯菌菌株中，61.1%对美罗培南敏感，99.3%在头孢他啶-阿维巴坦MIC≤4μg/ml时被抑制。在铜绿假单胞菌菌株中，头孢他啶-阿维巴坦MIC≤8μg/ml时，96.9%被抑制，美罗培南、头孢他啶和哌拉西林-他唑巴坦的敏感率分别为82.0%、83.2%和78.3%。头孢他啶-阿维巴坦是针对美罗培南不敏感的铜绿假单胞菌测试的最具活性的化合物（MIC50/MIC90，4/16μg/ml；87.3%在≤8μg/ml时被抑制）。不动杆菌属（头孢他啶-阿维巴坦MIC50/MIC90，16/>32μg/ml）对大多数测试药物显示出高耐药率。总之，头孢他啶-阿维巴坦对2012年从美国医院患者中分离出的大量当代革兰氏阴性杆菌具有强大活性，包括对大多数现有药物耐药的菌株，如产肺炎克雷伯菌碳青霉烯酶（KPC）的肠杆菌科细菌和美罗培南不敏感的铜绿假单胞菌。
