Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Clinical Laboratory, Hunan Province People's Hospital, Changsha, Hunan, China.
J Antimicrob Chemother. 2020 Feb 1;75(2):327-336. doi: 10.1093/jac/dkz446.
Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described.
We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015-17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated.
A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid.
CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.
产碳青霉烯酶高毒力肺炎克雷伯菌（CR-hvKP）在中国的报道日益增多。本研究描述了一项针对 CR-hvKP 的多中心纵向监测研究。
我们回顾性调查了 2015 年至 2017 年期间中国 56 个中心的耐碳青霉烯肺炎克雷伯菌（CRKP），并筛选了毒力基因（iucA、iroN、rmpA 和 rmpA2）是否存在毒力质粒。通过超黏液性、血清杀伤和大蜡螟致死实验，从携带所有 4 种毒力基因的菌株中鉴定出 CR-hvKP。还对 CR-hvKP 的荚膜分型、适应性和质粒特征进行了研究。
共收集了 1052 株 CRKP，其中 34.2%（360/1052）携带毒力基因，其中 72 株携带 4 种毒力基因。55 株（76.4%）被大蜡螟感染模型认为是 CR-hvKP，其中以 KPC-2 产 K64-ST11 最为常见（80%，44/55）。CR-hvKP 的流行率在不同地区差异很大，河南（25.4%，17/67）和山东（25.8%，25/97）最高。2015 年至 2017 年间，KPC-2 产 ST11 菌株中 CR-hvKP 的比例显著增加，从 2.1%（3/141）增加到 7.0%（23/329）（P=0.045）。令人担忧的是，与经典 CRKP 相比，CR-hvKP 的生长没有差异（P=0.7028），这表明其传播的风险增加。该杂交毒力和耐药性基因编码质粒源于 pLVPK，耐药质粒携带 blaKPC-2，表明在高毒力和高耐药质粒之间存在进化关系。
CR-hvKP 的检出频率高于以往预期，尤其是在 KPC-2 产 ST11 中。由于适应性成本有限，高毒力的传播可能非常迅速。此外，还发现耐药基因进化为高毒力质粒，这对公共卫生和感染控制提出了重大挑战。
