Cefepime-zidebactam therapy for extensively drug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae infection as a bridge to liver transplantation

Background Infections due to antimicrobial-resistant Gram-negative organisms present increasingly difficult therapeutic challenges, especially in the presence of metallo-β-lactamases. We present the case of a patient with cholangitis due to Pseudomonas aeruginosa and Klebsiella pneumoniae isolates that developed cefiderocol resistance on therapy treated successfully with cefepime-zidebactam. Methods Serial clinical isolates recovered from biliary fluid and ascitic fluid were tested for susceptibility to cefiderocol, aztreonam-avibactam, cefepime-taniborbactam, cefepime-zidebactam, and cefiderocol-xeruborbactam by broth microdilution. Whole-genome sequencing was performed to identify resistance determinants. An emergency investigational new drug application was authorized by the United States Food and Drug Administration for the compassionate use of cefepime-zidebactam based on susceptibility test results. Results Index isolates of P. aeruginosa (IMP positive) and K. pneumoniae (NDM-5, OXA-232 positive) tested susceptible to cefiderocol by disk diffusion in the clinical microbiology laboratory. The patient was treated with a regimen of cefiderocol and eravacycline, with persistent fever and development of hepatic microabscesses on imaging. Compassionate use cefepime-zidebactam therapy was initiated the day prior to liver transplantation and continued for a total of 14 days due to positive ascitic fluid cultures obtained during the operation. The K. pneumoniae and P. aeruginosa were cefiderocol resistant by broth microdilution. Cefepime-zidebactam remained active with MICs of 8/8 mg/L and 32/32 mg/L, respectively. The patient did well post-transplant and resumed chemotherapy. Conclusion Antimicrobial therapy with cefepime-zidebactam along with source control allowed successful liver transplantation in a patient with cefiderocol-resistant K. pneumoniae and P. aeruginosa. Cefepime-zidebactam may be a therapeutic option for extensively drug-resistant Gram-negative organisms.