Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0030122. doi: 10.1128/aac.00301-22. Epub 2022 Jun 16.
Fluoroquinolones are potentially effective against Elizabethkingia anophelis. We investigated the MIC, mutant prevention concentration (MPC), and target gene mutations of fluoroquinolones in . Eighty-five s isolates were collected from five hospitals in Taiwan. The MIC and MPC of ciprofloxacin and levofloxacin were examined for all s except 17 isolates, in which ciprofloxacin MPC could not be determined due to drug precipitation caused by overly high drug concentration. Mutations in the quinolone resistance-determining regions of DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) in the clinical isolates and fluoroquinolone-selected mutants were examined. Overall, 23.5% and 71.8% of the isolates tested were susceptible to ciprofloxacin and levofloxacin, respectively. The MPC of ciprofloxacin was 128 mg/L, and the MPC of levofloxacin was 51.2 mg/L. The MPC/MIC ratio for ciprofloxacin was 64, whereas that for levofloxacin was 25.6. The coefficient of determination between the MPC and MIC for ciprofloxacin and levofloxacin was 0.72 and 0.56, respectively, in the linear regression analysis. Preexisting mutations in GyrA (S83I, S83R, and D87Y) were identified in 18 clinical isolates, all of which were resistant to both ciprofloxacin and levofloxacin. Additional amino acid substitutions in GyrA were identified in all ciprofloxacin- and levofloxacin-selected mutants. Furthermore, GyrB alterations (D431N or D431H) were found in nine levofloxacin-treated isolates. Given that maintaining the serum concentrations of fluoroquinolones above MPCs is impossible under presently recommended doses, the selection of mutant strains seems inevitable.
氟喹诺酮类药物对伊丽莎白菌具有潜在的疗效。我们研究了氟喹诺酮类药物对 85 株分离株的 MIC、突变预防浓度（MPC）和靶基因突变。除 17 株分离株外，所有分离株均检测了环丙沙星和左氧氟沙星的 MIC 和 MPC，其中 17 株由于药物浓度过高导致药物沉淀，无法确定环丙沙星 MPC。检测了临床分离株和氟喹诺酮选择突变株中 DNA 拓扑异构酶（gyrase 的 GyrA 和 GyrB）和拓扑异构酶 IV（ParC 和 ParE）喹诺酮耐药决定区的突变。总体而言，23.5%和 71.8%的分离株对环丙沙星和左氧氟沙星敏感。环丙沙星的 MPC 为 128mg/L，左氧氟沙星的 MPC 为 51.2mg/L。环丙沙星的 MPC/MIC 比值为 64，左氧氟沙星的 MPC/MIC 比值为 25.6。线性回归分析中环丙沙星和左氧氟沙星的 MPC 与 MIC 之间的决定系数分别为 0.72 和 0.56。在 18 株临床分离株中发现了 GyrA （S83I、S83R 和 D87Y）的预先存在突变，这些分离株对环丙沙星和左氧氟沙星均耐药。在所有环丙沙星和左氧氟沙星选择的突变株中均发现了 GyrA 的额外氨基酸取代。此外，在 9 株左氧氟沙星治疗的分离株中发现了 GyrB 改变（D431N 或 D431H）。由于在目前推荐的剂量下，氟喹诺酮类药物的血清浓度保持在 MPC 以上是不可能的，因此选择突变株似乎是不可避免的。
