Yu Wei, Zhang Hui, Zhu Ying, Jia PeiYao, Xu YingChun, Yang QiWen
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Int J Antimicrob Agents. 2023 Apr;61(4):106741. doi: 10.1016/j.ijantimicag.2023.106741. Epub 2023 Feb 1.
Ceftolozane/tazobactam (an antipseudomonal cephalosporin) in combination with a well-established β-lactamase inhibitor has not been approved to date in clinical practice in China. The aim of this study was to evaluate the in-vitro activity of ceftolozane/tazobactam and comparator agents against Pseudomonas aeruginosa with various resistance patterns. P. aeruginosa (n=2178) specimens were collected from multiple sources in seven geographic regions of China between 2016 and 2019. All isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and minimum inhibitory concentrations of various antimicrobial agents (ceftolozane/tazobactam, amikacin, tobramycin, ceftazidime, cefepime, colistin, levofloxacin, aztreonam, meropenem, imipenem and piperacillin/tazobactam) were determined using the Clinical and Laboratory Standards Institute's broth microdilution method. P. aeruginosa demonstrated considerably high rates of multi-drug resistance (MDR, 57.3%), extensive drug resistance (XDR, 43.5%) and difficult-to-treat resistance (DTR, 16.8%). The overall susceptibility of P. aeruginosa to ceftolozane/tazobactam was 81.9%, and ceftolozane/tazobactam showed diverse activity against the three resistant subsets, ranging from 28.5% against DTR P. aeruginosa to 68.9% against MDR P. aeruginosa. P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa derived from the East (Jiangzhe area) region maintained significantly lower susceptibility to ceftolozane/tazobactam compared with P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa from other regions. The susceptibility rates of P. aeruginosa isolated from diverse sources to ceftolozane/tazobactam were similar to isolates from bloodstream infections, with the highest being 88.6%. Compared with other antimicrobial agents, ceftolozane/tazobactam was more active than the β-lactams tested but was slightly less active than amikacin. Amikacin demonstrated the best activity against P. aeruginosa and the three resistant subsets. Ceftolozane/tazobactam demonstrated considerable in-vitro activity against P. aeruginosa, MDR P. aeruginosa, XDR P. aeruginosa and DTR P. aeruginosa, indicating that it could be an optional therapeutic agent against P. aeruginosa.
头孢洛扎/他唑巴坦(一种抗假单胞菌头孢菌素)与一种成熟的β-内酰胺酶抑制剂联合使用,目前在中国临床实践中尚未获批。本研究的目的是评估头孢洛扎/他唑巴坦及对照药物对具有不同耐药模式的铜绿假单胞菌的体外活性。2016年至2019年间,从中国七个地理区域的多个来源收集了2178株铜绿假单胞菌标本。所有分离株均通过基质辅助激光解吸/电离飞行时间质谱进行鉴定,并使用临床和实验室标准协会的肉汤微量稀释法测定各种抗菌药物(头孢洛扎/他唑巴坦、阿米卡星、妥布霉素、头孢他啶、头孢吡肟、黏菌素、左氧氟沙星、氨曲南、美罗培南、亚胺培南和哌拉西林/他唑巴坦)的最低抑菌浓度。铜绿假单胞菌表现出相当高的多重耐药率(MDR,57.3%)、广泛耐药率(XDR,43.5%)和难治性耐药率(DTR,16.8%)。铜绿假单胞菌对头孢洛扎/他唑巴坦的总体敏感性为81.9%,头孢洛扎/他唑巴坦对三个耐药亚组表现出不同的活性,对DTR铜绿假单胞菌的活性为28.5%,对MDR铜绿假单胞菌的活性为68.9%。与来自其他地区的铜绿假单胞菌、MDR铜绿假单胞菌、XDR铜绿假单胞菌和DTR铜绿假单胞菌相比,来自东部(江浙地区)的铜绿假单胞菌、MDR铜绿假单胞菌、XDR铜绿假单胞菌和DTR铜绿假单胞菌对头孢洛扎/他唑巴坦的敏感性显著较低。从不同来源分离的铜绿假单胞菌对头孢洛扎/他唑巴坦的敏感率与血流感染分离株相似,最高为88.6%。与其他抗菌药物相比,头孢洛扎/他唑巴坦比所测试的β-内酰胺类药物活性更强,但比阿米卡星活性稍弱。阿米卡星对铜绿假单胞菌和三个耐药亚组表现出最佳活性。头孢洛扎/他唑巴坦对铜绿假单胞菌、MDR铜绿假单胞菌、XDR铜绿假单胞菌和DTR铜绿假单胞菌表现出相当的体外活性,表明它可能是治疗铜绿假单胞菌的一种可选治疗药物。