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埃及癌症患者分离出的革兰氏阴性病原菌中的质粒介导喹诺酮耐药性

Plasmid-Mediated Quinolone Resistance in Gram-Negative Pathogens Isolated from Cancer Patients in Egypt.

作者信息

Hamed Samira M, Aboshanab Khaled M A, El-Mahallawy Hadir A, Helmy Mai M, Ashour Mohamed S, Elkhatib Walid F

机构信息

1 Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts , 6th of October, Egypt .

2 Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University , Cairo, Egypt .

出版信息

Microb Drug Resist. 2018 Nov;24(9):1316-1325. doi: 10.1089/mdr.2017.0354. Epub 2018 Mar 13.

Abstract

Fluoroquinolones (FQs) are the drugs of choice for prophylaxis of bacterial infections in immunocompromised cancer patients. This study aimed to investigate FQ resistance and the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants in 239 Gram-negative isolates collected at a tertiary care cancer hospital in Cairo, Egypt. Disc diffusion and broth microdilution tests showed that 70.7% of the isolates were nonsusceptible to ciprofloxacin (MIC = 64 μg/ml). Polymerase chain reaction (PCR) revealed that 53.6% of the isolates carried at least one PMQR determinant, of which 23.4% were susceptible to ciprofloxacin. The most prevalent gene, aac(6')-Ib-cr, was identified in 36.8% of the isolates, while qnr genes were harbored by 31.0% (qnrS, 24.3%; qnrB, 7.1%, and qnrA, 0.4%). The oqxAB genes were only detected in Klebsiella sp. isolates (92.5%). PMQR determinants were more likely detectable among isolates recovered from pediatric patients than adults (59.3% vs. 43.8%) and were significantly associated with ceftriaxone and gentamicin resistance. A combined genetic analysis using random amplified polymorphic DNA-PCR and enterobacterial repetitive intergenic consensus-PCR showed that most of the qnr-positive isolates were not clonal. Findings of the current study raised concerns about the efficacy of prophylactic use of FQs in cancer patients in our region. It also demonstrates the possible role of PMQR-positive ciprofloxacin-susceptible isolates in the dissemination of resistance to other antimicrobial agents and the urgent need to reconsider the existing FQ breakpoints defined by the Clinical and Laboratory Standards Institute.

摘要

氟喹诺酮类药物(FQs)是免疫功能低下的癌症患者预防细菌感染的首选药物。本研究旨在调查埃及开罗一家三级护理癌症医院收集的239株革兰氏阴性菌分离株中氟喹诺酮耐药性及质粒介导的喹诺酮耐药性(PMQR)决定簇的流行情况。纸片扩散法和肉汤微量稀释试验表明,70.7%的分离株对环丙沙星不敏感(MIC = 64μg/ml)。聚合酶链反应(PCR)显示,53.6%的分离株携带至少一种PMQR决定簇,其中23.4%对环丙沙星敏感。最常见的基因aac(6')-Ib-cr在36.8%的分离株中被鉴定出来,而qnr基因存在于31.0%的分离株中(qnrS,24.3%;qnrB,7.1%,qnrA,0.4%)。oqxAB基因仅在克雷伯菌属分离株中检测到(92.5%)。在从儿科患者中分离出的菌株中比在成人中更有可能检测到PMQR决定簇(59.3%对43.8%),并且与头孢曲松和庆大霉素耐药性显著相关。使用随机扩增多态性DNA-PCR和肠杆菌重复基因间共有序列-PCR的联合基因分析表明,大多数qnr阳性分离株不是克隆性的。本研究结果引发了对本地区癌症患者预防性使用氟喹诺酮类药物疗效的担忧。它还证明了PMQR阳性且对环丙沙星敏感的分离株在其他抗菌药物耐药性传播中的可能作用,以及迫切需要重新考虑临床和实验室标准协会定义的现有氟喹诺酮类药物断点。

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