Pharmacist-Led Stewardship Improved HAP and VAP Prescribing in Trial
Key Takeaways
- Higher day-3 prescribing appropriateness was observed with pharmacist-led antimicrobial stewardship than with standard care.
- Higher clinical cure and lower antimicrobial exposure, readmission, and antimicrobial-related adverse events were reported in the intervention group.
- Findings were directionally similar in HAP and VAP subgroups, and pharmacist recommendations were accepted at a high overall rate.
The prospective randomized controlled trial ran for 18 months, from April 2023 to October 2024, at Khyber Teaching Hospital in Peshawar, Pakistan. The hospital lacked a formal structured antimicrobial stewardship program at baseline, although updated institutional guidelines and some informal stewardship-related practices were already in place, and 700 adults were enrolled, with 366 assigned to intervention and 334 to control. Hospital-acquired pneumonia accounted for 59.1% of the cohort, ventilator-associated pneumonia for 40.9%, and all participants completed the study. Pharmacists with postgraduate clinical pharmacy training and at least 2 years of experience performed daily medication review, culture-guided optimization, therapeutic drug monitoring, duration optimization, adverse event monitoring, and multidisciplinary communication, while standard care included access to the updated guidelines but no systematic pharmacist review or intervention. The primary endpoint was appropriate antimicrobial prescribing on day 3, defined by an all-or-nothing assessment of drug selection, dosing, route, duration, and de-escalation or combination therapy, making it a stringent early stewardship measure.
Secondary efficacy findings favored the intervention in the published trial results. Clinical cure at day 14 was 84.4% with pharmacist-led stewardship and 74.3% with standard care, with an odds ratio of 1.86, a 95% confidence interval of 1.27-2.72, and p=0.001. Mean hospital stay was 14.64 ± 5.48 days versus 17.47 ± 7.22 days, a mean difference of -2.83 days, while total antimicrobial treatment duration was 11.98 ± 5.80 versus 13.45 ± 6.12 days, a 10.9% reduction, with p<0.001 for both comparisons. Antimicrobial consumption also fell from 79.52 to 69.86 defined daily doses per 100 patient-days, a 12.1% reduction. Together, these results paired higher clinical cure with lower antimicrobial exposure and shorter hospitalization.
Additional outcomes also favored the intervention group. Thirty-day readmission was 7.7% versus 21.3%, with an odds ratio of 0.30, a 95% confidence interval of 0.19-0.48, and p<0.001. Antimicrobial-related adverse events occurred in 8.7% versus 14.1%, with an odds ratio of 0.58, a 95% confidence interval of 0.36-0.94, and p=0.026; categories included nephrotoxicity, hepatotoxicity, hematological toxicity, C. difficile infection, and drug-drug interactions. No significant interaction was reported between HAP and VAP across outcomes, although both subgroups showed similar directional results. Overall acceptance of pharmacist recommendations was 89.7%, and the most frequent actions were de-escalation, dose optimization, and duration optimization. Across the reported measures, the intervention was associated with more appropriate prescribing and lower antimicrobial burden.
The trial was bounded by several design features. It was conducted at a single tertiary center, participants and treating teams were not blinded, and outcome assessors were blinded where possible. Follow-up did not include prospective resistance surveillance or 90-day mortality. Within those limits, the randomized comparison showed a consistent pattern across prescribing, exposure, and clinical outcomes.