Emergence of Hypervirulent Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae Isolates in a Chinese Tertiary Hospital
Emergence of Hypervirulent Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae Isolates in a Chinese Tertiary Hospital
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DOI：
10.2147/idr.s257477
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Li, Dan;Liao, Wenjian;Zhang, Wei
简介：碳青霉烯类耐药高毒力肺炎克雷伯菌（CR-hvKP）在全球范围内的报告越来越多，但头孢他啶/阿维巴坦（CAZ/AVI）耐药hvKP分离株很少观察到。方法：对2016年3月至2018年3月从某大学医院临床分离的CRKP菌株进行药敏试验、耐药基因检测、多位点序列分型、SDS-PAGE和脉冲场凝胶电泳分析。通过PCR在所有CAZ/AVI耐药CRKP分离株中筛选pLVPK相关遗传位点（rmpA 2、terW、iutA和锡尔斯），以确定是否存在毒力质粒。通过荚膜分型、血清杀灭试验、大蜡螟致死试验和小鼠致死试验，对携带4种毒力基因的232株CRKP进行CAZ/AVI耐药hvKP鉴定。总体而言，在8.2%（19/232）的CRKP分离株中发现CAZ/AVI耐药，分离株来自既往无CAZ/AVI治疗史的患者。其中63.2%（12/19）为产金属β-内酰胺酶的K.肺炎克雷伯菌产碳青霉烯酶（KPC）占52.6%（10/19）;肺炎克雷伯氏菌（KPC-KP）中，有26.3%（5/19）同时产生MBL和KPC。碳青霉烯酶的存在仅在ompk 35和ompk 36不存在时促进CAZ/AVI最小抑制浓度的非常高的增加。令人震惊的是，9个分离株具有所有4个毒力基因的毒力质粒的存在。根据G.结论：新出现的耐CAZ/AVI的KP株高毒力菌株对公众健康构成严重威胁，应加强临床认识和流行病学监测。
Introduction: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is increasingly reported worldwide, but ceftazidime/avibactam (CAZ/AVI)-resistant hvKP isolates have rarely been observed. We attempted to characterize them in clinical CRKP isolates collected from a university hospital in China from March 2016 to March 2018.Methods: All isolates were analyzed by antimicrobial susceptibility testing, molecular detection of antibiotic resistance determinants, multilocus sequence typing (MLST), SDS-PAGE, and pulsed-field gel electrophoresis (PFGE). The pLVPK-related genetic loci (rmpA2, terW, iutA, and silS) were screened in all CAZ/AVI-resistant CRKP isolates for the presence of virulence plasmids by PCR. Capsule typing, serum killing assay, Galleria mellonella lethality experiments, and mouse lethality assay were conducted to identify CAZ/AVI-resistant hvKP among isolates that carried all four virulence genes.Results: A total of 232 CRKP isolates were collected. Overall, CAZ/AVI-resistance was found in 8.2% (19/232) CRKP isolates isolated from patients with no history of previous CAZ/AVI-based treatment. Among these, 63.2% (12/19) were metallo-beta-lactamase-producing K. pneumoniae (MBL-KP), 52.6% (10/19) were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP), and 26.3% (5/19) produced both MBL and KPC. The presence of carbapenemase promoted a very high increase in CAZ/AVI minimum inhibitory concentration only when ompk35 and ompk36 were absent. Alarmingly, nine isolates had all four virulence genes for the presence of virulence plasmids. All nine isolates were considered to be CAZ/AVI-resistant hvKP according to the G. mellonella infection model and mouse lethality assay, with ST23 being the most common type (55.6%, 5/9).Conclusion: The newly emerged hypervirulent CAZ/AVI-resistant KP strain might cause a serious threat to public health, suggesting an urgent need for enhanced clinical awareness and epidemiologic surveillance.