Pharmacogenomics of antimicrobial agents

Abstract

Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.

Keywords: antibacterials; antifungals; antimalarials; antivirals; pharmacogenomics.

Figure 1. Complex relationships between various drug, pathogen and host factors affecting antimicrobial treatment outcome

ADR: Adverse drug reaction; PD: Pharmacogenomics; PK: Pharmacokinetics Modified and reproduced with written permission from Pharmacogenomics and Personalized Medicine [9].

Figure 2. Isoniazid metabolic pathways

GST: Gluthathione-S-transferase; NAT: N-acetyl transferase.