Aminoglycosides such as gentamicin act via concentration-dependent killing and are limited by nephrotoxicity and ototoxicity, both of which can be reduced by once-daily dosing. Vancomycin infusion reactions, termed red man syndrome, result from histamine release during rapid infusion, producing flushing and pruritus rather than a true IgE-mediated allergy; slowing the infusion prevents the reaction. The cross-reactivity risk between penicillins and cephalosporins has historically been quoted as around 10%, but modern estimates place the actual rate closer to 1-2%, particularly with first-generation cephalosporins sharing a similar R1 side chain, and even lower with third- and fourth-generation agents.
Antivirals for herpesviruses center on acyclovir, which is activated by viral thymidine kinase to its triphosphate form and acts as a DNA chain terminator, primarily against HSV and VZV, with nephrotoxicity if patients are not adequately hydrated. Ganciclovir is the CMV-specific counterpart, much more potent against CMV but considerably more myelosuppressive. The four first-line anti-tuberculosis drugs each carry distinct toxicities: isoniazid causes hepatotoxicity and peripheral neuropathy from vitamin B6 depletion, so B6 (pyridoxine) supplementation is given prophylactically; rifampin is a potent CYP450 inducer (reducing levels of many drugs including oral contraceptives and warfarin) and produces benign orange discoloration of body fluids; ethambutol's signature toxicity is optic neuritis with red-green color blindness; and pyrazinamide causes both hepatotoxicity and hyperuricemia that can precipitate gout.