Clinical Epidemiological Analysis of the Genotypic Spectrum and Mortality Risk in Carbapenem‐Resistant Klebsiella pneumoniae (CRKP) Infections

Background Carbapenem‐resistant Klebsiella pneumoniae (CRKP) has become a global public health threat, with significantly increased morbidity and mortality among high‐risk inpatients. High‐risk genotypes of CRKP, primarily including K. pneumoniae carbapenemase (KPC), oxacillinase‐48–like (OXA‐48–like), New Delhi metallo‐β‐lactamase (NDM), imipenemase (IMP), and Verona integron–encoded metallo‐β‐lactamase (VIM) types (hereafter referred to as KPC, OXA‐48–like, NDM, IMP, and VIM, respectively) as defined by international consensus due to their association with enhanced transmission, drug resistance, and mortality risk, have emerged as key challenges in clinical practice. However, the impact of different genotypic types of CRKP on mortality risk and their regional epidemiology remain unclear. Methods This systematic review and meta‐analysis were conducted according to the PRISMA guidelines and registered in PROSPERO (CRD420251150672). PubMed, Embase, and Web of Science were systematically searched for original studies up to September 9, 2025. Eligible studies reported genotypic types of CRKP (such as KPC, OXA‐48–like, NDM, IMP, and VIM) and patient mortality. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random‐effects model. Subgroup analyses were performed by the genotype and region. Risk of bias was assessed using the ROBINS‐I tool. Results A total of 58 studies involving various countries and regions were included. The pooled analysis showed that CRKP infection with high‐risk genotypes—defined in this study primarily as KPC and OXA‐48–like types due to their strong association with increased transmission, drug resistance, and mortality—was significantly associated with increased all‐cause mortality (pooled OR = 3.08, 95% CI: 2.44–3.88, p < 0.0001; I 2 = 63.4%). Subgroup analysis revealed that KPC‐type CRKP infection had a higher mortality risk (pooled OR = 3.57, 95% CI: 2.82–4.53), with the effect more pronounced in China (OR = 3.85) than in other countries (OR = 3.04). The OXA‐48–like genotype also showed increased mortality risk (OR = 2.57, 95% CI: 1.47–4.50), while evidence for other genotypes such as NDM, IMP, and VIM was limited. Sensitivity analysis and publication bias tests supported the robustness of the results. GRADE assessment indicated moderate evidence for KPC but lower quality for other genotypes. Conclusions High‐risk genotypes of CRKP—defined in this study as KPC and OXA‐48–like due to their strong association with increased transmission, drug resistance, and mortality—are associated with significantly increased mortality risk in infected patients, especially in China. These findings support risk stratification and personalized management of high‐risk patients and provide evidence for regional prevention and control strategies. Further multicenter and mechanistic studies are warranted to improve clinical management and patient outcomes.