Clinical and genomic insights into persistent carbapenem-resistant Klebsiella pneumoniae bacteremia: risk factors, resistance mechanisms, and treatment challenges.

INTRODUCTION

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of nosocomial infections with high mortality rates. Persistent bacteremia, indicative of treatment failure, poses significant clinical challenges. This study aimed to identify clinical parameters for persistent CRKP bacteremia while exploring microbial and genetic characteristics.

MATERIALS AND

METHODS

A case-control study was conducted on patients with CRKP bacteremia from January 2016 to July 2019 at a tertiary hospital in Taiwan. Clinical, demographic, and microbiological data were collected for 61 cases of persistent bacteremia and 122 matched controls without persistent infections. Conditional logistic regression was used to evaluate risk factors for persistent bacteremia. Whole-genome sequencing (WGS) was used to identify genotypes and factors mediating resistance and virulence in the strains.

RESULTS

Persistent CRKP bacteremia was independently associated with mechanical ventilation (adjusted odds ratio [aOR] 11.007, 95 % confidence interval [CI] 2.137-56.693), a lower Pitt bacteremia score (aOR 0.642, 95 % CI 0.494-0.835), and the use of colistin (aOR 11.18, 95 % CI 2.988-41.787) and tigecycline (aOR 16.42, 95 % 4.495-60.0) in definitive therapy. Strains from either group shared similar capsular types. WGS identified three dominant multidrug-resistant clones, ST11, ST307, and ST15, harboring carbapenemase and virulence factors encoding yersiniabactin. A strain of hypervirulent clone ST23 exhibited high virulence but lacked carbapenemase genes, suggesting alternative resistance mechanisms of CR phenotype.

CONCLUSIONS

Antimicrobial regimens with tigecycline and colistin were insufficient for effectively managing CRKP bacteremia. The convergence of resistance and virulence in prevalent clones demands the urgent introduction of novel therapeutics. Aggressive and tailored strategies are critical for improving outcomes in high-risk patients.