氟喹诺酮类耐药决定因子在中国血流感染碳青霉烯类耐药肺炎克雷伯菌临床分离株中的分布。
Distribution of fluoroquinolone resistance determinants in Carbapenem-resistant Klebsiella pneumoniae clinical isolates associated with bloodstream infections in China.
机构信息
Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, 330006, P. R. China.
Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, P. R. China.
出版信息
BMC Microbiol. 2021 Jun 2;21(1):164. doi: 10.1186/s12866-021-02238-7.
BACKGROUND
The rate of fluoroquinolone (FQ) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is high. The present study aimed to investigate the distribution of fluoroquinolone resistance determinants in clinical CRKP isolates associated with bloodstream infections (BSIs).
RESULTS
A total of 149 BSI-associated clinical CRKP isolates collected from 11 Chinese teaching hospitals from 2015 to 2018 were investigated for the prevalence of fluoroquinolone resistance determinants, including plasmid-mediated quinolone resistance (PMQR) genes and spontaneous mutations in the quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes. Among these 149 clinical CRKP isolates, 117 (78.5%) exhibited resistance to ciprofloxacin. The GyrA substitutions (Ser83 → IIe/Phe) and (Asp87 → Gly/Ala) were found among 112 (75.2%) of 149 isolates, while the substitution (Ser80 → IIe) of ParC was found in 111 (74.5%) of the 149 isolates. In total, 70.5% (105/149) of the CRKP isolates had at least two mutations within gyrA as well as a third mutation in parC. No mutations in the QRDRs were found in 31 ciprofloxacin susceptible CRKP isolates. Eighty-nine (56.9%) of 149 were found to carry PMQR genes including qnrS1 (43.0%), aac(6')-Ib-cr (16.1%), qnrB4 (6.0%), qnrB2 (2.7%), and qnrB1 (1.3%). Nine isolates contained two or more PMQR genes, with one carrying four [aac(6')-Ib-cr, qnr-S1, qnrB2, and qnrB4]. The co-existence rate of PMQR determinants and mutations in the QRDRs of gyrA and parC reached 68.5% (61/89). Seventy-four (83.1%, 74/89) PMQR-positive isolates harbored extended-spectrum beta-lactamase (ESBL)-encoding genes. Multilocus sequence typing (MLST) analysis demonstrated that the ST11 was the most prevalent STs in our study.
CONCLUSIONS
Mutations in the QRDRs of gyrA and parC were the key factors leading to the high prevalence of fluoroquinolone resistance among BSI-associated CRKP. The co-existence of PMQR genes and mutations in the QRDRs can increase the resistance level of CRKP to fluoroquinolones in clinical settings. ST11 CRKP isolates with identical QRDR substitution patterns were found throughout hospitals in China.
背景
碳青霉烯类耐药肺炎克雷伯菌（CRKP）对氟喹诺酮类药物的耐药率较高。本研究旨在调查与血流感染（BSI）相关的临床 CRKP 分离株中氟喹诺酮类耐药决定因素的分布。
结果
从 2015 年至 2018 年，11 家中国教学医院共收集了 149 例与 BSI 相关的临床 CRKP 分离株，用于研究氟喹诺酮类耐药决定因素，包括质粒介导的喹诺酮类耐药（PMQR）基因和gyrA 和 parC 基因喹诺酮类耐药决定区（QRDR）中的自发突变。在这 149 例临床 CRKP 分离株中，有 117 例（78.5%）对环丙沙星表现出耐药性。在 149 株分离株中，有 112 株（75.2%）存在 GyrA 取代（Ser83→IIe/Phe）和（Asp87→Gly/Ala），而 149 株分离株中有 111 株（74.5%）存在 ParC 的取代（Ser80→IIe）。总的来说，70.5%（105/149）的 CRKP 分离株在 gyrA 中有至少两个突变，在 parC 中有第三个突变。在 31 株对环丙沙星敏感的 CRKP 分离株中未发现 QRDR 突变。在 149 株分离株中，有 89 株（56.9%）携带 PMQR 基因，包括 qnrS1（43.0%）、aac(6')-Ib-cr（16.1%）、qnrB4（6.0%）、qnrB2（2.7%）和 qnrB1（1.3%）。有 9 株分离株携带两种或两种以上的 PMQR 基因，其中一株携带四种[aac(6')-Ib-cr、qnr-S1、qnrB2 和 qnrB4]。PMQR 决定因素与 gyrA 和 parC 的 QRDR 突变的共存率达到 68.5%（61/89）。74 株（83.1%，74/89）PMQR 阳性分离株携带超广谱β-内酰胺酶（ESBL）编码基因。多位点序列分型（MLST）分析表明，ST11 是本研究中最常见的 STs。
结论
gyrA 和 parC 的 QRDR 突变是导致与血流感染相关的 CRKP 中氟喹诺酮类药物高耐药率的关键因素。PMQR 基因与 QRDR 突变的共存可增加临床 CRKP 对氟喹诺酮类药物的耐药水平。在中国的医院中发现了具有相同 QRDR 取代模式的 ST11 CRKP 分离株。
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