Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom.
Service of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
Clin Infect Dis. 2020 Oct 23;71(7):e141-e150. doi: 10.1093/cid/ciz1095.
Carbapenemase-producing Klebsiella pneumoniae has become a global priority, not least in low- and middle-income countries. Here, we report the emergence and clinical impact of a novel Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) sequence type (ST) 16 clone in a clonal complex (CC) 258-endemic setting.
In a teaching Brazilian hospital, a retrospective cohort of adult KPC-KP bloodstream infection (BSI) cases (January 2014 to December 2016) was established to study the molecular epidemiology and its impact on outcome (30-day all-cause mortality). KPC-KP isolates underwent multilocus sequence typing. Survival analysis between ST/CC groups and risk factors for fatal outcome (logistic regression) were evaluated. Representative isolates underwent whole-genome sequencing and had their virulence tested in a Galleria larvae model.
One hundred sixty-five unique KPC-KP BSI cases were identified. CC258 was predominant (66%), followed by ST16 (12%). The overall 30-day mortality rate was 60%; in contrast, 95% of ST16 cases were fatal. Patients' severity scores were high and baseline clinical variables were not statistically different across STs. In multivariate analysis, ST16 (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-202.8; P = .008) and septic shock (OR, 11.9; 95% CI, 4.2-34.1; P < .001) were independent risk factors for fatal outcome. The ST16 clone carried up to 14 resistance genes, including blaKPC-2 in an IncFIBpQIL plasmid, KL51 capsule, and yersiniabactin virulence determinants. The ST16 clone was highly pathogenic in the larvae model.
Mortality rates were high in this KPC-KP BSI cohort, where CC258 is endemic. An emerging ST16 clone was associated with high mortality. Our results suggest that even in endemic settings, highly virulent clones can rapidly emerge demanding constant monitoring.
产碳青霉烯酶肺炎克雷伯菌已成为全球关注的重点，尤其是在中低收入国家。在这里，我们报告了一种新型肺炎克雷伯菌碳青霉烯酶（KPC-KP）产酶肺炎克雷伯菌（KPC-KP）序列型（ST）16 克隆在克隆复合体（CC）258 流行地区的出现和临床影响。
在一家教学巴西医院，建立了一个成人 KPC-KP 血流感染（BSI）病例的回顾性队列（2014 年 1 月至 2016 年 12 月），以研究分子流行病学及其对预后（30 天全因死亡率）的影响。对 KPC-KP 分离株进行多位点序列分型。通过逻辑回归评估 ST/CC 组之间的生存分析和致命结局的危险因素。代表性分离株进行全基因组测序，并在金龟子幼虫模型中进行其毒力测试。
共确定了 165 例独特的 KPC-KP BSI 病例。CC258 占主导地位（66%），其次是 ST16（12%）。总的 30 天死亡率为 60%；相比之下，ST16 病例的死亡率为 95%。患者的严重程度评分较高，基线临床变量在 ST 之间无统计学差异。多变量分析显示，ST16（比值比[OR]，21.4；95%置信区间[CI]，2.3-202.8；P =.008）和感染性休克（OR，11.9；95%CI，4.2-34.1；P <.001）是致命结局的独立危险因素。ST16 克隆携带多达 14 种耐药基因，包括 IncFIBpQIL 质粒上的 blaKPC-2、KL51 荚膜和耶尔森菌素毒力决定因素。ST16 克隆在幼虫模型中具有高度致病性。
在 KPC-KP BSI 流行地区，CC258 是地方性的，死亡率很高。一种新兴的 ST16 克隆与高死亡率相关。我们的结果表明，即使在流行地区，高致病性克隆也可能迅速出现，需要持续监测。
