Carlo Tascini, Luca Montanari, Francesca Patriarca, Michela Bulfoni, Renato Fanin, Simone Giuliano, Jacopo Angelini, Paolo Gaibani
Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae causes difficult-to-treat bloodstream infections in patients with haematological malignancies, particularly after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Carbapenems remain reliable, but their anti-anaerobic activity may aggravate intestinal dysbiosis and increase selection pressure for carbapenem resistance. Cefepime-enmetazobactam is a novel fourth-generation cephalosporin/β-lactamase inhibitor combination active against many class A ESBL-producing Enterobacterales. We describe a profoundly immunocompromised patient with acute myeloid leukaemia after allo-HSCT, grade III steroid-refractory gastrointestinal graft-versus-host disease, and intestinal colonization by an ESBL-producing K. pneumoniae isolate resistant to ceftolozane-tazobactam. The patient developed persistent bacteraemia and right pyelonephritis with small renal abscess-like lesions. Meropenem was rapidly de-escalated to cefepime-enmetazobactam, with temporary adjunctive fosfomycin and subsequently tigecycline. Blood-culture time to positivity progressively lengthened from 1.18 h to 16 h before cultures became negative. Serial cefepime therapeutic drug monitoring permitted repeated assessment of exposure and neurological toxicity risk. Whole-genome sequencing identified K. pneumoniae ST307 carrying blaCTX-M-15, blaTEM-1, blaSHV-28, and blaOXA-1, together with multiple resistance determinants and a large conjugative plasmid. This case describes the use of cefepime-enmetazobactam as part of a targeted carbapenem-sparing strategy for invasive ESBL-producing K. pneumoniae infection in a highly immunocompromised allo-HSCT recipient.