Abstract
Antimicrobial resistance (AMR) has emerged as a critical global health threat, particularly in pediatric populations where empirical antibiotic use is common and diagnostic limitations persist. In parallel, pharmacogenomic variability is increasingly recognized as a key determinant of inter-individual differences in drug metabolism, therapeutic response, and adverse outcomes. This study examined the relationship between pharmacogenomic variability and antimicrobial resistance patterns among pediatric patients in tertiary care hospitals of Pakistan. A quantitative cross-sectional analytical design was employed to assess pediatric patients diagnosed with bacterial infections and receiving antibiotic therapy. Data were collected through clinical record review, microbiological susceptibility testing, and selected pharmacogenomic profiling. Descriptive and inferential statistical analyses, including chi-square tests and multivariate logistic regression, were applied to determine associations between genetic variability, antibiotic response, and resistance outcomes. Findings indicated a high prevalence of multidrug-resistant and ESBL-producing Gram-negative pathogens, particularly Escherichia coli and Klebsiella pneumoniae. Significant associations were observed between pharmacogenomic variants (including CYP450, ABCB1, and SLCO1B1 polymorphisms) and treatment failure, prolonged infection duration, and increased likelihood of resistant infections. Pharmacogenomic variability emerged as an independent predictor of antimicrobial resistance after adjusting for clinical confounders such as ICU admission and prior antibiotic exposure. The study highlights the dual influence of host genetic variability and microbial resistance mechanisms in shaping therapeutic outcomes in pediatric settings. The results underscore the need for integrating pharmacogenomic insights into antimicrobial stewardship programs to support precision-based antibiotic therapy in resource-limited healthcare systems. Such integration may improve clinical outcomes, reduce treatment failure, and mitigate the growing burden of antimicrobial resistance in pediatric populations