Yu Hanbing, Ma Deyu, Liu Bo, Yang Suqing, Lin Qiuxia, Yu Renlin, Jia Xiaojiong, Niu Siqiang, Zhang Qun, Huang Shifeng
Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Med (Lausanne). 2022 Mar 14;9:827474. doi: 10.3389/fmed.2022.827474. eCollection 2022.
The dissemination of carbapenemase-producing (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, = 0.003). was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric isolates carried , while 82.0% (41/50) of the adult strains harbored . The ratio of in children (37.5%) was significantly higher than that in adults (12.8%, = 0.002). In both populations, the majority of expressed , particularly . With statistical significance, was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, was the most common CPE-BSIs pathogen in both populations, with NDM-producing and KPC-producing ST11 being the most prevalent species in children and adults, respectively. was more prevalent in children than in adults, yet was the most common carbapenem-resistant mechanism in in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible partial synergy of the amikacin and fosfomycin combination.
鉴于产碳青霉烯酶肠杆菌科细菌（CPE）的治疗选择有限，其传播令人担忧。CPE血流感染（BSIs）在成人中死亡率很高，而全球范围内关于儿童CPE-BSIs的数据很少。我们全面探讨了儿童和成人CPE-BSIs在临床和微生物学特征上的差异。收集了48例儿童和78例成人CPE-BSIs病例。CPE-BSIs患儿的全因30天死亡率（14.6%，7/48）显著低于成人患者（42.3%，33/78，P = 0.001）。经验性使用替加环素作为有效药物治疗的成人亚组30天粗死亡率（63.3%，19/30）显著高于未使用替加环素治疗的亚组（29.2%，14/48，P = 0.003）。大肠埃希菌是儿童（45.8%，22/48）和成人（64.1%，50/78）中最常见的菌种，且各人群中碳青霉烯酶基因存在差异：95.4%（21/22）的儿童大肠埃希菌分离株携带blaNDM，而82.0%（41/50）的成人菌株携带blaKPC。儿童中肺炎克雷伯菌的比例（37.5%）显著高于成人（12.8%，P = 0.002）。在两个群体中，大多数肺炎克雷伯菌表达blaKPC，尤其是ST11型。具有统计学意义的是，blaNDM在儿童中（95.8%，46/48）比在成人中（34.6%，27/78）更为常见。儿童多重异质性耐药表型的发生率高达87.5%，而成人则低得多（57.1%）。针对一株儿童产碳青霉烯酶大肠埃希菌分离株的琼脂稀释棋盘实验表明，阿米卡星和磷霉素联合使用具有相加作用。总体而言，大肠埃希菌是两个群体中最常见的CPE-BSIs病原体，产NDM的大肠埃希菌和产KPC的ST11型肺炎克雷伯菌分别是儿童和成人中最常见的菌种。blaNDM在儿童中比在成人中更普遍，但blaKPC是两个群体中肺炎克雷伯菌最常见的耐碳青霉烯机制。在来自不同宿主群体的不同病原体菌种中发现的广泛多重异质性耐药组合特征应为未来联合治疗方案的设计提供良好基础。需要对更多不同菌种的CPE分离株进行进一步研究，以评估阿米卡星和磷霉素联合使用可能存在的部分协同作用。
