Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Int J Antimicrob Agents. 2017 Sep;50(3):491-495. doi: 10.1016/j.ijantimicag.2017.04.010. Epub 2017 Jun 28.
This study explored the prevalence of urinary tract tuberculosis (UTB) and whether efflux pump activation accounts for resistance to moxifloxacin in Taiwan. Of 3034 patients with culture-confirmed TB from 2005-2012, 47 patients (1.5%) with UTB were included in this study. Minimum inhibitory concentrations (MICs) of moxifloxacin were determined in the presence and absence of efflux pump inhibitors (EPIs), including verapamil, reserpine and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). EPI responders were defined as isolates with at least a four-fold reduction in MICs in the presence of EPIs. Among the 47 isolates, 24 (51.1%) were resistant to ofloxacin and 22 (46.8%) were resistant to moxifloxacin by the agar proportion method. Among the 22 moxifloxacin-resistant isolates, 19 (86.4%) had low-level resistance (MIC = 1.0-2.0 mg/L). Patients with prior exposure to fluoroquinolones were more likely than non-exposed patients to have moxifloxacin-resistant isolates [14/22 (63.6%) vs. 8/25 (32.0%); P = 0.030]. All 3 isolates with high-level moxifloxacin resistance (MIC ≥ 4.0 mg/L) had mutations in the gyrA or gyrB genes; however, among the 19 isolates with low-level resistance, only 1 (5.3%) had a mutation in the gyrA gene. Among the 19 isolates with low-level moxifloxacin resistance, 16 isolates (84.2%) were EPIs responders, but none of the high-level resistant isolates were EPIs responders. Approximately one-half (46.8%) of the isolates from patients with UTB were resistant to moxifloxacin, and activation of efflux pumps accounted for most low-level moxifloxacin-resistant isolates.
本研究旨在探讨在台湾，尿路结核（UTB）的流行情况，以及外排泵的激活是否导致莫西沙星耐药。在 2005 年至 2012 年间，从 3034 例培养确诊的结核病患者中，纳入了 47 例 UTB 患者（1.5%）。本研究测定了莫西沙星的最低抑菌浓度（MIC），并在存在和不存在外排泵抑制剂（EPI）的情况下进行了测定，EPI 包括维拉帕米、利血平、羰基氰化物 3-氯苯腙（CCCP）。EPI 应答者被定义为在外排泵抑制剂存在的情况下，MIC 至少降低 4 倍的分离株。在 47 株分离株中，24 株（51.1%）对氧氟沙星耐药，22 株（46.8%）对莫西沙星耐药（琼脂比例法）。在 22 株莫西沙星耐药分离株中，19 株（86.4%）为低水平耐药（MIC=1.0-2.0mg/L）。有氟喹诺酮类药物暴露史的患者比无暴露史的患者更有可能出现莫西沙星耐药分离株[14/22（63.6%）比 8/25（32.0%）；P=0.030]。所有 3 株高水平莫西沙星耐药（MIC≥4.0mg/L）的分离株均在 gyrA 或 gyrB 基因上有突变；然而，在 19 株低水平耐药的分离株中，只有 1 株（5.3%）gyrA 基因有突变。在 19 株低水平莫西沙星耐药的分离株中，16 株（84.2%）为 EPI 应答者，但没有一株高水平耐药的分离株为 EPI 应答者。大约一半（46.8%）的 UTB 患者分离株对莫西沙星耐药，外排泵的激活导致了大多数低水平莫西沙星耐药分离株的产生。
