Successful use of cefepime/zidebactam in deep-seated infections due to extensively drug-resistant Pseudomonas aeruginosa: A case series.

OBJECTIVE

There is a paucity of safe and effective treatment options for extensively drug resistant (XDR) Gram-negative pathogens that often harbor varied resistance mechanisms concurrently. Cefepime/zidebactam (FEP/ZID) is a novel β-lactam/β-lactam enhancer (BL-BLE) combination, currently in Phase 3 trials, that has been shown to be effective against such difficult to treat resistant isolates in-vitro studies and scattered case reports. We present a series of deep seated infections due to XDR Pseudomonas Aeruginosa (PsA), successfully treated with FEP/ZID under compassionate use.

METHODS

Between September 2023 and May 2024, using clinico-radiographic and microbiologic (phenotypic drug susceptibility and whole genome sequencing) data, we identified five XDR PsA related infections that could not be safely treated with currently available antibiotics. All patients received FEP/ZID after obtaining informed consent and necessary approvals.

RESULTS

Four cases involved osteoarticular disease while the fifth was an endovascular graft infection. Clinical specimens yielded XDR PsA isolates that harbored varied (enzymatic and non-enzymatic) resistance mechanisms to anti-pseudomonal cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and newer β-lactam/β-lactamase inhibitors. All isolates were susceptible to FEP/ZID and were treated with the same for 2-6 wk. Clinico-radiographic assessments confirmed significant resolution of lesions in all cases. There were with no drug-related adverse events.

CONCLUSIONS

The in-vitro susceptibility of our XDR PsA isolates to FEP/ZID translated to a successful clinical outcome in our series of deep-seated infections. FEP/ZID is a potential safe and effective treatment option for such serious Gram-negative infections.