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

We report a fatal case of carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteremia following exposure to non-carbapenem antimicrobials in a 54-year-old man with lymphoma. Following cord blood transplantation (defined as day 0), the patient developed febrile neutropenia on day 7, which was initially managed with ceftolozane–tazobactam based on pre-transplant fecal culture susceptibility. After developing grade III acute graft-versus-host disease, CRKP bacteremia was confirmed on day 30, with resistance to both ceftolozane–tazobactam and carbapenems. Despite intensive antimicrobial therapy, the patient died on day 43. Whole-genome sequencing of the isolated CRKP strains revealed multiple β-lactamase genes, including blaSHV-28, blaCTX-M-15, blaOXA-1, and blaTEM-1B, as well as an ompK36 mutation conferring resistance to both ceftolozane–tazobactam and carbapenems. Additionally, increased transcription of blaSHV-28 was observed in isolates after ceftolozane–tazobactam exposure. This case highlights the rapid emergence of multidrug resistance during treatment. A comprehensive antimicrobial stewardship approach is essential, particularly in immunocompromised hosts.