Clinical risk factors and genomic characterization of carbapenem-resistant Klebsiella pneumoniae infections in a traditional Chinese medicine hospital.

BACKGROUND

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly hypervirulent multidrug-resistant strains, has become a major cause of healthcare-associated infections with high mortality. However, molecular characteristics and mortality risk factors for CRKP infections in Chinese Traditional Medicine hospitals remain poorly understood.

METHODS

We conducted a retrospective study of patients with microbiologically confirmed CRKP infections at a tertiary TCM hospital between 2019 and 2022. Multivariate logistic regression was used to assess independent risk factors for mortality. We performed whole-genome sequencing on 102 CRKP isolates (2022) to characterize antimicrobial resistance determinants, virulence factors, and phylogenetic relationships.

RESULTS

In our cohort of 233 CRKP-infected patients (76 non-survivors, 157 survivors), multivariate analysis identified four independent predictors of in-hospital mortality: multiple organ dysfunction syndrome (aOR 3.69, 95% CI 1.28-10.61; P = 0.015), sepsis (aOR 3.04, 95% CI 1.30-7.12; P = 0.011), invasive mechanical ventilation (aOR 5.95, 95% CI 2.78-12.75; P<0.001), and ICU admission (aOR 4.10, 95% CI 1.55-10.84; P = 0.005). Genomic analysis identified ST11-KL64 (55.9%, 57/102) and ST15-KL19 (21.6%, 22/102) as dominant clones, alongside novel strains ST1658-KL60 and ST3345-KL8. The prevalent plasmid was IncFIB(K) (85.3%), followed by IncHI1B (66.7%); IncFII(pHN7A8) (28.4%) was exclusive to ST11. The predominant capsular type was KL64:O2a. Carbapenem resistance was primarily driven by bla KPC-2 (92.2%, 94/102). In addition to the dominant wild-type bla KPC-2, we identified two other bla KPC-2 variants: one strain harboring bla KPC-33, and one strain harboring a novel bla KPC-2 variant with an L169T substitution (CTG→ACG) in the Ω-loop domain, which confers ceftazidime-avibactam resistance. Eighty-two isolates (80.4%) exhibited high virulence (score 4), characterized by aerobactin/salmochelin co-occurrence with yersiniabactin (ybt 9/ICEKp3 predominant), but lacking colibactin.

CONCLUSIONS

Our study highlights the predominance of ST11-KL64 and ST15-KL19 CRKP clones in a TCM hospital setting, with bla KPC-2 as the main driver of carbapenem resistance. High virulence and multidrug resistance are common features, contributing to significant mortality. These findings underscore the need for targeted infection control and treatment strategies in TCM hospitals.