Piperacillin-tazobactam/meropenem vs colistin/meropenem for carbapenem-resistant Klebsiella Pneumoniae-related ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a major concern in ICUs, particularly with carbapenem-resistant Klebsiella pneumoniae (CRKP). Dual beta-lactam antibiotic regimens may improve outcomes compared to traditional therapies. This study evaluates the efficacy and safety of meropenem/piperacillin-tazobactam versus meropenem/colistin for CRKP-related VAP. Primary outcomes are the change in Clinical Pulmonary Infection Score (CPIS) from baseline to Day 7, ICU length of stay, and ventilator-free days. Secondary outcomes include 28-day mortality, bacterial clearance, and renal or hepatic adverse events.

METHODS: This randomized, open-label clinical trial will enroll 88 ICU patients with confirmed CRKP-related VAP. Participants will be randomly assigned to receive either meropenem/piperacillin-tazobactam or meropenem/colistin. The primary endpoints are improvement in CPIS, ICU length of stay, and ventilator-free days. Secondary endpoints include bacterial clearance and clinical recovery over 28 days. Safety will be assessed via renal and hepatic function monitoring and adverse event recording. Randomization and data collection follow SPIRIT 2013 guidelines to ensure rigor and transparency.

DISCUSSION: Studies indicate that antibiotic combinations, particularly dual beta-lactam therapies, may enhance efficacy against resistant pathogens, including CRKP. While limited studies exist on dual beta-lactam regimens, recent findings suggest promising outcomes with combinations like meropenem/piperacillin-tazobactam. This study aims to provide robust evidence to address the gap in research and improve clinical guidelines for VAP management in ICU settings.

TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCT; available at https://irct.behdasht.gov.ir/ ; ID: IRCT20240229061132N1). Registered on March 16, 2025.