Pharmacogenomics-Guided Precision Antimicrobial Therapy: From Genetic Variability to Personalized Treatment

Abstract

Pharmacogenomics (PGx) is a new branch of precision medicine that studies how genetic diversity influences differences in antimicrobial efficacy, drug exposure, toxicity, and treatment response. Although traditional antimicrobial therapy has significantly improved outcomes in infectious diseases, interindividual heterogeneity caused by pharmacokinetic, pharmacodynamic, clinical, pathogen-related, and genetic variables can all contribute to treatment failure or adverse drug reactions. This article outlines the pharmacogenomic foundation of antimicrobial response, which includes genetic diversity in drug-metabolizing enzymes, transporters, immune-related genes, and drug targets. Clinically relevant uses include HLA-B57:01 screening for abacavir hypersensitivity, MT-RNR1-associated aminoglycoside ototoxicity, CYP2B6-related efavirenz exposure, G6PD-associated toxicity, NAT2-related isoniazid metabolism, and CYP2C19-guided voriconazole therapy. The integration of pharmacogenomics with therapeutic drug monitoring, pharmacokinetic/pharmacodynamic modeling, model-informed precision dosing, fast diagnostics, artificial intelligence, and multi-omics may further assist personalized antimicrobial therapy. Pharmacogenomic testing tools ranging from targeted PCR and microarrays to next-generation and whole-genome sequencing open up new avenues for clinical use. India's wide genetic diversity and population-specific pharmacogenomic variations underscore the importance of representative genomic databases, standardized testing panels, clinical recommendations, and outcome-based validation. Despite significant advances, evidence for many antimicrobial gene-drug interactions is still sparse, and implementation is hampered by costs, infrastructure, interpretation, professional education, and unequal population representation. Future research should focus on varied populations, prospective clinical validation, integration with electronic health records, and evidence-based precision antimicrobial management.