Evolution of carbapenem-resistant Klebsiella pneumoniae after ceftolozane-tazobactam exposure in a patient after cord blood transplantation: A case report.

OBJECTIVE

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have a poor prognosis, particularly in immunocompromised patients. While carbapenemase production is the primary resistance mechanism in carbapenem-resistant K. pneumoniae (CRKP), other mechanisms may contribute synergistically to carbapenem resistance. Here, we describe a case in which extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, initially susceptible to carbapenems, acquired carbapenem resistance without carbapenemase production following ceftolozane-tazobactam exposure.

METHODS

Whole-genome sequencing was performed on ESBL-producing K. pneumoniae strains detected during the clinical course to investigate the relationship between the genetic characteristics and antimicrobial susceptibility, particularly to ceftolozane-tazobactam and carbapenems. Changes in the transcription levels of the beta-lactamase genes were also analysed using reverse transcription quantitative PCR (RT-qPCR).

RESULTS

Active surveillance stool culture before cord blood transplantation (CBT) identified colonisation with an ESBL-producing K. pneumoniae strain. Febrile neutropenia occurred on day 7 after CBT and was treated empirically with ceftolozane-tazobactam. Fatal bacteraemia developed on day 30 after CBT due to a carbapenemase-negative isolate resistant to both ceftolozane-tazobactam and carbapenems. Whole-genome sequencing analysis revealed that K. pneumoniae ST307 strains harbouring blaCTX-M-15, blaSHV-28 and blaTEM-1B acquired a nonsense mutation in ompK36 following ceftolozane-tazobactam exposure. RT-qPCR analysis documented a significant increase in blaSHV-28 transcription after ceftolozane-tazobactam exposure.

CONCLUSIONS

This case demonstrates that K. pneumoniae without carbapenemase production can acquire carbapenem resistance through a combined resistance mechanisms following exposure to non-carbapenem antibiotics. Antimicrobial stewardship must be implemented comprehensively, not focused solely on specific antibiotics.