In penicillin-allergic patients with Pseudomonas infection, which antibiotic should be used in place of piperacillin?

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When a patient has a penicillin allergy and a Pseudomonas infection, substitute the penicillin with a non-penicillin agent that still has strong anti-pseudomonal activity. Cefepime fits this need as a fourth-generation cephalosporin with reliable Pseudomonas coverage and reasonable Gram-positive activity. The cross-reactivity risk with penicillins is low enough in most cases to justify its use as a safe alternative, making it a preferred choice over continuing with a penicillin-class drug.

Meropenem is also active against Pseudomonas, but as a carbapenem, it’s often reserved for more complicated or resistant infections. Ceftazidime can cover Pseudomonas as well but has less Gram-positive activity and a narrower overall spectrum compared with cefepime. Hence, cefepime is the best substitution in this scenario.