Emergence of Hypervirulent ST11-K64 Klebsiella pneumoniae Poses a Serious Clinical Threat in Older Patients

Abstract

The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC−2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 μg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant “superbugs” is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.

Successful treatment of acute respiratory distress syndrome caused by hypervirulent Klebsiella pneumoniae with extracorporeal membrane oxygenation and continuous renal replacement therapy: A case report and literature review

“…The hvKP can cause severe community or hospital-acquired infections ( 49 , 50 ). The risk factors include renal insufficiency ( 42 , 51 ), diabetes ( 52 ), age ≥ 65 years ( 1 ), and chronic alcoholism ( 53 ). HvKP causes tissue invasive infection, often involving multiple sites.…”

“…The emergence of hypervirulent Klebsiella pneumoniae (hvKP) poses a significant challenge to public health ( 1 ). Additionally, hvKP can cause fatal systemic infections.…”

Genomic Evolution of ST11 Carbapenem-Resistant Klebsiella pneumoniae from 2011 to 2020 Based on Data from the Pathosystems Resource Integration Center

“…It is undeniable that the evolution of KL47 to KL64 is gradually becoming the mainstream trend, and ST11-KL64 CRKP will account for an increasing proportion of all ST11 types. Additionally, KL64 is linked to high virulence [ 29 ], suggesting that ST11 carbapenem-resistant K. pneumoniae is evolving into a highly virulence strain.…”

Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae

“…OmpK36 can reduce the sensitivity of ESBL and AmpC β-lactamase of CRKP and is closely related to the resistance of CRKP to carbapenems (Wang et al, 2009). In a retrospective study with 28 cases of CRKP infections Yao et al, 2015;Zhang et al, 2015;Liu et al, 2016;Zhang et al, 2016;Liu et al, 2017;Zhan et al, 2017;Dong et al, 2018;Feng et al, 2018;Huang et al, 2018;Wei et al, 2018;Gu et al, 2018a,b;Dong et al, 2019;Liu and Su, 2019;Shen et al, 2019;Shu et al, 2019;Xu et al, 2019;Yuan et al, 2019;Zhou et al, 2019;Li et al, 2019b;Hao et al, 2020;Jin et al, 2020;Liu et al, 2020;Yang et al, 2020;Zhang et al, 2020;Zheng et al, 2020;Zhou et al, 2020;Li et al, 2020a,b;Huang et al, 2021;Jin et al, 2021;Liu et al, 2021;Shao et al, 2021;Su et al, 2021;Xie et al, 2021;Yan et al, 2021;Zhang et al, 2021;Zhao et al, 2021;Zhou et al, 2021;Li et al, 2021a,b;Yang et al, 2021b;Wei et al, 2022;Zhou et al, 2022; f...…”

“…The recent emergence of ST11 is the most frequent clone for CR-hvKP globally, especially in China (Wu et al, 2017;Liao et al, 2020;Wei et al, 2022). ST11 CR-hvKP can cause bacterial liver abscess (Yang et al, 2020;Cai et al, 2022), bacteremia and other infections, and it is a high-risk clinical pathogen that attracts worldwide attention (Wu et al, 2017).…”