Kinetics of antimicrobial activity.

Assessment of antimicrobial activity from standard in vitro minimum inhibitory and minimum bactericidal concentration determinations alone is incomplete. Rate of bacterial killing, effect of increasing concentration, sub-MIC effects, and degree of suppression of bacterial growth after limited exposure (post-antibiotic effect) more precisely describe the course of antimicrobial activity. Aminoglycoside antibiotics exhibit concentration-dependent bactericidal activity and a prolonged post-antibiotic effect. beta-Lactam antibiotics demonstrate more time-dependent killing and lack post-antibiotic effects, except with staphylococci. Most bacteriostatic antimicrobial agents also produce post-antibiotic suppression of growth. Studies in different animal infection models with a variety of organisms suggest that beta-lactams are more efficacious with continuous dosing, whereas the efficacy of aminoglycosides is relatively independent of dosing regimen, even when administered once daily. Knowledge of the kinetics of antimicrobial action is useful in predicting optimal dosage regimens.