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Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin\/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin\/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin\/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin\/tazobactam (OR 1.14 95% CI [1.01\u20131.27], <jats:italic>p<\/jats:italic>\u2009=\u20090.03), (OR 1.14 95% CI [1.03\u20131.26], <jats:italic>p<\/jats:italic>\u2009=\u20090.009), (OR 1.1 95% CI [1.01\u20131.22], <jats:italic>p<\/jats:italic>\u2009=\u20090.039) and (OR 1.13 95% CI [1.03\u20131.24], <jats:italic>p<\/jats:italic>\u2009=\u20090.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin\/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.<\/jats:p>","DOI":"10.1038\/s41598-024-64444-3","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T10:04:01Z","timestamp":1718100241000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A targeted likelihood estimation comparing cefepime and piperacillin\/tazobactam in critically ill patients with community-acquired pneumonia (CAP)"],"prefix":"10.1038","volume":"14","author":[{"given":"Cristian C.","family":"Serrano-Mayorga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Duque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa D.","family":"Ib\u00e1\u00f1ez-Prada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Garcia-Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda P. 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