Assessing antimicrobial utilization and costs, and correlating biological markers with adverse events in ICU patients: An effort towards antimicrobial stewardship.

Abstract

Antimicrobials can worsen redox and inflammatory imbalances, leading to adverse drug events (ADEs). No comprehensive analysis of ADEs across antimicrobial classes with biological markers has been done in India. This study aimed to assess antimicrobial use patterns, costs, and ADEs among ICU patients and to explore the relationship between oxidative stress and inflammatory biomarkers and ADEs from antimicrobial therapy. Over 2 years at a tertiary hospital, 303 ICU patients on systemic antimicrobials for over 24 hours were studied. ADEs were documented until discharge. Antimicrobial use was assessed with the ATC classification and expressed as defined daily doses per 100 bed days. ADE causality and severity were evaluated with Naranjo's and Hartwig-Siegel scales. Correlations with oxidative stress (MDA, GSH, Nrf-2, 8-isoprostane, ADMA) and inflammatory biomarkers (IL-6, IL-10, hsCRP) were also analyzed. A total of 739 antimicrobials were administered, averaging 2.4 per patient. Most were for infections (86.46%), with empirical therapy common (55.44%). Cultures showed no growth in 76.73% and bacterial growth in 20.86%, primarily respiratory infections (41.91%). Piperacillin-Tazobactam was the most used fixed-dose combination (14.9% of prescriptions), costing 720,273 INR (8783.80 USD). The total antimicrobial cost was 2,524,311 INR (30,784.30 USD). Eight mild to moderate ADEs (2.64%) were observed. IL-6 and hsCRP positively correlated with ADEs, while IL-10 negatively correlated. Oxidative stress markers MDA, ADMA, and 8-isoprostane were positively correlated with ADEs, while GSH and Nrf-2 were negatively correlated. The study underscores the need for antimicrobial stewardship and reveals significant correlations between biomarkers and ADEs, suggesting new prevention and management strategies.