Activity of Cefepime/Enmetazobactam in Carbapenem-Resistant Gram-Negative Bacteria: Real-World Evidence from a German Tertiary Care Center

Carbapenem-resistant gram-negative organisms are a rising global concern, and novel therapeutic options are urgently needed. Cefepime/enmetazobactam (FEP/META), approved for the treatment of complicated urinary tract infections, could be an important asset in clinical care. This study aimed to determine the activity of FEP/META in a collection of genetically characterized carbapenem-resistant Enterobacterales and <i>Pseudomonas aeruginosa</i>. FEP/META susceptibility was tested in 104 carbapenem-resistant clinical isolates (<i>Escherichia coli</i>, 14; <i>Klebsiella pneumoniae</i>, 30; other Enterobacterales [oEs]), 29; <i>P. aeruginosa</i>, 31) as tested by agar disk diffusion according to the European Committee on Antimicrobial Susceptibility Testing protocols. A carbapenemase gene was identified in 75% (78/104) of all isolates. A cefepime-resistant phenotype was detected in 89% (93/104) of all isolates. FEP/META was active against 29% (30/104) of all isolates tested, including 2 <i>E. coli</i>, 5 <i>K. pneumoniae</i>, 11 oEs, and 12 <i>P. aeruginosa</i> isolates. Twenty-two out of 78 (28%) of all carbapenemase-positive and 8 out of 26 (31%) of all carbapenemase-negative isolates were tested susceptible to FEP/META, respectively. META restored FEP susceptibility in 22/93 (24%) of cefepime-resistant isolates (16 carbapenemase-positive, 6 carbapenemase-negative), indicating a direct META effect to restore cefepime susceptibility. In conclusion, this study provides evidence for activity of FEP/META in selected carbapenem-resistant Enterobacterales and <i>P. aeruginosa</i>. Susceptibility varied across resistance genotypes and included isolates carrying resistance determinants formally not targeted by META. FEP/META could be an option for carbapenem-resistant organisms if other recommended therapies fail.