Aim: This study was aimed to determine rational use of antibiotic therapy in ICU patients and its impact on clinical outcomes and mortality rate.

Methods: This was a retrospective, longitudinal (cohort) study including 100 patients in the ICU of the largest tertiary care hospital of the capital city of Pakistan.

Results: It was observed that empiric antibiotic therapy was initiated in 68% of patients, while culture sensitivity test was conducted for only 19% of patients. Thirty-percent of patients developed nosocomial infections and empiric antibiotic therapy was not initiated for those patients (P<0.05). Irrational antibiotic prescribing was observed in 86% of patients, and among them, 96.5% mortality was observed (P<0.05). The overall mortality rate was 83%; even higher mortality rates were observed in patients on a ventilator, patients with serious drug-drug interactions, and patients prescribed with irrational antibiotics or nephrotoxic drugs. Adverse clinical outcomes leading to death were observed to be significantly associated (P<0.05) with irrational antibiotic prescribing, nonadjustment of doses of nephrotoxic drugs, use of steroids, and major drug-drug interactions.