Anti-infective agents are some of the most widely used therapeutic drugs
worldwide. Overall, the most common serious adverse events attributable to antiinfective
agents include liver injury, nephrotoxicity, hypersensitivity reactions, cardiac
arrhythmias, drug-drug interactions and therapeutic failure. In clinical practice, serious
problems of toxicity limit the usefulness of antimicrobial drugs.
In order to improve the design of clinical trials and better conceptualize research plans
for the development of anti-infective drugs, it is important to take into consideration
cutting-edge drug safety approaches that can be implemented during discovery and
early phase studies, as well as promising methods and models for clinical research
advancement. In the present text, we describe a holistic perspective inspired by
chemoinformatics, systems biology, and predictive clinical pharmacology, to discuss
the utility of in silico methods, preclinical models, genomics, translational biomarkers
and postmarketing surveillance strategies for safety evaluation and risk detection during
anti-infective drug development.
Keywords: Adverse effect, adverse reaction, AMES test, animal model, antiinfective
drug, biomarkers, cardiotoxicity, chemoinformatics, clinical trial, Cramer
rules, drug development, drug discovery, drug-induced toxicity, environmental risk
assessment, hepatotoxicity, humanized mice, nephrotoxicity, pharmacogenomics,
pharmacovigilance, preclinical study, quantitative structure-activity relationship
(QSAR), systems toxicology, translational medicine, verhaar scheme, zebrafish.
