Antimicrobial safety and tolerability: Differences and dilemmas

The adverse drug reactions associated with antimicrobials have become a top ic of major importance and concern in the last few years. Antimicrobial tox icity may take many forms, varying from mild, transient phenomena to dramat ic, life-threatening events such as seizures or cardiac arrhythmias. We rev iew the toxicity of antimicrobials in general and of the fluoroquinolones i n particular and attempt to explain the adverse events by use of structure- adverse event relationships where possible. There are currently 5 main mech anisms that can be invoked to explain antimicrobial toxicity: direct effect s, hypersensitivity, changes in microbial flora, drug interactions, and mic robial lysis. The adverse drug reactions seen with fluoroquinolones are exp lained on the basis of these 5 mechanisms. The various organ systems affect ed by the fluoroquinolones are considered; then individual members of the f luoroquinolone class are reviewed. The unexpected and dramatic problems enc ountered with temafloxacin and trovafloxacin are discussed as well.