Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, 9/F, Clinical Sciences Building, Shatin, Hong Kong SAR, China.
Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):3183-9. doi: 10.1007/s10096-012-1683-x. Epub 2012 Jun 29.
Plasmid-mediated quinolone resistance (qnr) genes confer low-level resistance but provide background for selection of highly-resistant strains. We investigated their prevalence and significance in clinical Enterobacteriaceae bacteremic isolates in Hong Kong. A prospective, hospital-based study was conducted (January 2008 to March 2009). Consecutive, non-duplicate blood isolates of extended-spectrum-β-lactamase (ESBL) and/or plasmid-mediated AmpC (PMAmpC) β-lactamase-producing Enterobacteriaceae were collected and subjected to qnr genes detection using multiplex PCR. Direct sequencing was performed to characterize the qnr and the co-existing bla genes. Clinical and microbiological variables, including antimicrobial resistance profiles, were compared between infections by 'qnr-positive' and 'qnr-negative' Enterobacteriaceae. Altogether 199 ESBL/PMAmpC-producing Enterobacteriaceae isolates were studied. qnr genes were detected in 20 % (qnrB, n = 24; qnrS, n = 16; qnrA, n = 0), of which 85% were Klebsiella spp. There was a strong association with PMAmpC genes (qnrB and DHA-1; p < 0.001). 'qnr-positive' isolates were more commonly hospital-acquired (60.0% vs 35.8%; adjusted OR 2.68, 95%CI 1.32-5.46) and multidrug-resistant (e.g. amoxicillin-clavulanate 90-100%, piperacillin-tazobactam 40-57%, ceftazidime 53-78%; sulfamethoxazole/trimethoprim 60-70%; ciprofloxacin 53-65%, levofloxacin 35-48%). Patients with 'qnr-positive' Enterobacteriaceae bacteremia had a higher 30-day mortality (45% vs 22%, p = 0.003). High Pitt bacteremia score, development of pneumonia, and failure to receive susceptible fluoroquinolone (adjusted HR 4.27; 95%CI 1.45-12.61) or carbapenem (adjusted HR 3.04; 95%CI 1.49-6.20) treatment were independent factors associated with death. A high proportion of ESBL/PMAmpC-producing Enterobacteriaceae (typically Klebsiella) bacteremic isolates carried qnr. These strains were multidrug-resistant, which was associated with inappropriate treatment and high fatality. Further dissemination of qnr and selection of fluoroquinolone/β-lactam-resistant strains should be closely monitored and controlled.
质粒介导的喹诺酮耐药（qnr）基因赋予了细菌对低水平抗生素的耐药性，但同时也为高度耐药菌株的选择提供了条件。我们调查了 qnr 基因在香港临床肠杆菌科菌血症分离株中的流行情况及其意义。这是一项前瞻性、基于医院的研究（2008 年 1 月至 2009 年 3 月）。收集了连续的、非重复的产超广谱β-内酰胺酶（ESBL）和/或质粒介导的 AmpC（PMAmpC）β-内酰胺酶的肠杆菌科血培养分离株，并使用多重 PCR 检测 qnr 基因。通过直接测序来鉴定 qnr 基因和共存的 bla 基因。比较了 qnr 阳性和 qnr 阴性肠杆菌科感染患者的临床和微生物学变量，包括抗生素耐药谱。共研究了 199 株产 ESBL/PMAmpC 的肠杆菌科分离株。在 20%的分离株中检测到了 qnr 基因（qnrB，n=24；qnrS，n=16；qnrA，n=0），其中 85%为肺炎克雷伯菌。qnr 基因与 PMAmpC 基因（qnrB 和 DHA-1；p<0.001）密切相关。qnr 阳性分离株更常见于医院获得性感染（60.0%比 35.8%；调整后的 OR 2.68，95%CI 1.32-5.46）和多重耐药（如阿莫西林-克拉维酸 90-100%，哌拉西林-他唑巴坦 40-57%，头孢他啶 53-78%；磺胺甲恶唑/甲氧苄啶 60-70%；环丙沙星 53-65%，左氧氟沙星 35-48%）。qnr 阳性肠杆菌科菌血症患者的 30 天死亡率较高（45%比 22%，p=0.003）。高 Pitt 菌血症评分、肺炎的发生以及未能接受敏感氟喹诺酮（调整后的 HR 4.27；95%CI 1.45-12.61）或碳青霉烯（调整后的 HR 3.04；95%CI 1.49-6.20）治疗是与死亡相关的独立因素。相当一部分产 ESBL/PMAmpC 的肠杆菌科（通常为肺炎克雷伯菌）菌血症分离株携带 qnr 基因。这些菌株对多种药物耐药，这与不恰当的治疗和高死亡率有关。应密切监测和控制 qnr 的进一步传播和氟喹诺酮/β-内酰胺耐药株的选择。
