Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Infectious Diseases, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University, Changwon, South Korea.
Antimicrob Agents Chemother. 2017 Dec 21;62(1). doi: 10.1128/AAC.01970-17. Print 2018 Jan.
Although carbapenems are effective for treating serious multidrug-resistant infections, carbapenem-resistant (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168-172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for , , , , , and by PCR. In the prior study, expression of , , and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 non-carbapenemase-producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillin-tazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased and increased expression (5.1% versus 25.6%, = 0.025, and 4.3% versus 34.8%, = 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased and increased expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.
虽然碳青霉烯类药物对治疗严重的多重耐药感染非常有效，但现在全球都有报道称出现了耐碳青霉烯类肠杆菌科细菌（CRPA）。头孢洛扎他唑巴坦（C/T）对许多多重耐药分离株具有活性。我们评估了 C/T 的活性，并使用经过充分表征的非碳青霉烯酶产生的 CRPA 分离株集，比较了其与头孢他啶-阿维巴坦（C/A）的活性。42 株非碳青霉烯酶产生的 CRPA 分离株来自先前的一项研究（J.Y. Lee 和 K.S. Ko，《国际抗菌药物杂志》40：168-172，2012 年，https://doi.org/10.1016/j.ijantimicag.2012.04.004），包括在之前的研究中通过 PCR 检测均显示阴性的 、 、 、 、 和 。在之前的研究中，通过定量逆转录-PCR 已经确定了 、 和几种外排泵基因的表达。在这里，根据临床和实验室标准协会（CLSI）指南，通过肉汤微量稀释法确定了抗菌药物敏感性。使用三种 C/T 和 C/A 敏感的 CRPA 分离株进行时间杀伤曲线测定。在 42 株非碳青霉烯酶产生的 CRPA 分离株中，对 C/T 的总体敏感性为 95.2%，而对 C/A、头孢他啶、哌拉西林-他唑巴坦、头孢吡肟和美罗培南的敏感性分别为 71.4%、42.9%、23.8%、21.4%和 2.4%。在表达水平降低和增加的分离株中，C/T 的耐药率显著低于 C/A（分别为 5.1%比 25.6%， = 0.025 和 4.3%比 34.8%， = 0.022）。在时间杀伤曲线研究中，C/T 对表达水平降低和增加的分离株的杀菌作用弱于 C/A。C/T 对 95.2%的非碳青霉烯酶产生的 CRPA 临床分离株有效。未发现 C/T MIC 值与特定的突变驱动的耐药机制之间存在明显的相关性。
