Sader Helio S, Farrell David J, Castanheira Mariana, Flamm Robert K, Jones Ronald N
JMI Laboratories, North Liberty, IA 52317, USA
JMI Laboratories, North Liberty, IA 52317, USA.
J Antimicrob Chemother. 2014 Oct;69(10):2713-22. doi: 10.1093/jac/dku184. Epub 2014 Jun 10.
To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against contemporary Gram-negative bacteria. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor.
A total of 10 532 Gram-negative organisms (2191 Pseudomonas aeruginosa and 8341 Enterobacteriaceae) were consecutively collected from 31 medical centres located in 13 European countries plus Turkey and Israel. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A9 document and the results interpreted according to EUCAST as well as CLSI breakpoint criteria. Selected ceftazidime- and/or meropenem-resistant P. aeruginosa isolates were screened for the presence of β-lactamase genes by PCR.
P. aeruginosa exhibited high rates of multidrug-resistant (31.9%) and extensively drug-resistant (24.6%) isolates and 11.6% of isolates were susceptible only to colistin. When tested against P. aeruginosa, ceftolozane/tazobactam (MIC(50), 1 mg/L) was generally 4-fold more active than ceftazidime (MIC(50), 4 mg/L) and inhibited >90% of isolates with an MIC of ≤8 mg/L in nine countries. In contrast, the highest susceptibility rates observed for ceftazidime and meropenem, respectively, were 86.0%/86.0% (UK) and 85.2%/86.1% (Ireland) (67.2%/67.1% overall). Ceftolozane/tazobactam (MIC(50/90), 0.25/2 mg/L; 93.7% and 95.2% inhibited at ≤4 and ≤8 mg/L, respectively), meropenem [MIC(50/90), ≤0.06/≤0.06 mg/L; 98.0% susceptible (EUCAST)] and tigecycline [MIC(50/90), 0.12/1 mg/L; 94.1% susceptible (EUCAST)] were the most active compounds tested against Enterobacteriaceae.
Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.
评估头孢洛扎/他唑巴坦及对照药物对当代革兰氏阴性菌的体外活性。头孢洛扎/他唑巴坦是一种抗假单胞菌头孢菌素与一种成熟的β-内酰胺酶抑制剂的组合。
从位于13个欧洲国家以及土耳其和以色列的31个医疗中心连续收集了10532株革兰氏阴性菌（2191株铜绿假单胞菌和8341株肠杆菌科细菌）。按照CLSI M07-A9文件所述的肉汤微量稀释法检测这些细菌的敏感性，并根据EUCAST以及CLSI的折点标准解释结果。通过PCR筛选选定的对头孢他啶和/或美罗培南耐药的铜绿假单胞菌分离株中β-内酰胺酶基因的存在情况。
铜绿假单胞菌表现出较高比例的多重耐药（31.9%）和广泛耐药（24.6%）分离株，11.6%的分离株仅对黏菌素敏感。在针对铜绿假单胞菌进行测试时，头孢洛扎/他唑巴坦（MIC50，1 mg/L）的活性通常比头孢他啶（MIC50，4 mg/L）高4倍，并且在9个国家中抑制了>90%的MIC≤8 mg/L的分离株。相比之下，头孢他啶和美罗培南分别观察到的最高敏感率为86.0%/86.0%（英国）和85.2%/86.1%（爱尔兰）（总体为67.2%/67.1%）。头孢洛扎/他唑巴坦（MIC50/90，0.25/2 mg/L；在≤4 mg/L和≤8 mg/L时分别有93.7%和95.2%被抑制）、美罗培南[MIC50/90，≤0.06/≤0.06 mg/L；98.0%敏感（EUCAST）]和替加环素[MIC50/90，0.12/1 mg/L；94.1%敏感（EUCAST）]是针对肠杆菌科测试的最具活性的化合物。
头孢洛扎/他唑巴坦是针对铜绿假单胞菌测试的最具活性的β-内酰胺类药物，并且在针对肠杆菌科测试时，其体外活性高于目前可用的头孢菌素和哌拉西林/他唑巴坦。
