Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October, Giza, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, African Union Organization St. Abbassia, Cairo, 11566, Egypt.
Sci Rep. 2018 Aug 16;8(1):12268. doi: 10.1038/s41598-018-30756-4.
Fluoroquinolones have been used for prophylaxis against infections in cancer patients but their impact on the resistance mechanisms still require further investigation. To elucidate mechanisms underlying ciprofloxacin (CIP) resistance in Gram-negative pathogens causing infections to cancer patients, 169 isolates were investigated. Broth microdilution assays showed high-level CIP resistance in 89.3% of the isolates. Target site mutations were analyzed using PCR and DNA sequencing in 15 selected isolates. Of them, all had gyrA mutations (codons 83 and 87) with parC mutations (codons 80 and 84) in 93.3%. All isolates were screened for plasmid-mediated quinolone resistance (PMQR) genes and 56.8% of them were positive in this respect. Among PMQR genes, aac(6')-Ib-cr predominated (42.6%) while qnr genes were harbored by 32.5%. This comprised qnrS in 26.6% and qnrB in 6.5%. Clonality of the qnr-positive isolates using ERIC-PCR revealed that most of them were not clonal. CIP MIC reduction by CCCP, an efflux pump inhibitor, was studied and the results revealed that contribution of efflux activity was observed in 18.3% of the isolates. Furthermore, most fluoroquinolone resistance mechanisms were detected among Gram-negative isolates recovered from cancer patients. Target site mutations had the highest impact on CIP resistance as compared to PMQRs and efflux activity.
氟喹诺酮类药物已被用于预防癌症患者的感染，但它们对耐药机制的影响仍需进一步研究。为了阐明导致癌症患者感染的革兰氏阴性病原体对环丙沙星（CIP）耐药的机制，研究了 169 株分离株。肉汤微量稀释法显示，89.3%的分离株对 CIP 高度耐药。在 15 株选定的分离株中，使用 PCR 和 DNA 测序分析了靶位突变。其中，所有分离株均具有 gyrA 突变（密码子 83 和 87）和 parC 突变（密码子 80 和 84），占 93.3%。所有分离株均进行了质粒介导的喹诺酮耐药（PMQR）基因筛选，其中 56.8%的分离株呈阳性。在 PMQR 基因中，aac(6')-Ib-cr 占主导地位（42.6%），而 qnr 基因则占 32.5%。其中，qnrS 占 26.6%，qnrB 占 6.5%。使用 ERIC-PCR 对 qnr 阳性分离株的克隆性进行分析显示，它们大多数不是克隆的。用 CCCP（一种外排泵抑制剂）降低 CIP MIC，结果表明 18.3%的分离株存在外排活性。此外，在从癌症患者中分离的革兰氏阴性菌中检测到了大多数氟喹诺酮耐药机制。与 PMQR 和外排活性相比，靶位突变对 CIP 耐药的影响最大。
