1. Time-dependent antibiotics, including cephalosporins, penicillins, carbapenems, and glycopeptides. The time-dependent antibiotics exert optimal bactericidal effect when drug concentration are maintained above the minimum inhibitory concentration (MIC). Typically, concentrations are maintained at 2 to 4 times the MIC throughout the dosing interval. For these agents, higher concentrations do not result in greater kill of organisms. Furthermore, they tend to have minimal to no postantibiotic effect (PAE).

T >MIC

2. Concentration-dependent antibiotics, including fluoroquinolones, aminoglycosides, daptomycin, metronidazole, azithromycin, and ketolides. Concentration-dependent antibiotics achieve increasing bacterial kill with increasing levels of drug. In addition, these agents have an associated concentration-dependent PAE in which bactericidal action continues for a period of time after the antibiotic level falls below the MIC. The peak concentration and area under the concentration curve (AUC) determine efficacy of these antibiotics. For this group of drugs, concentrations (actually the peak concentration) of at least 10 times the MIC are needed for optimal bactericidal effect.

Peak:MIC ratio

3. Time-dependent and concentration-enhanced antibiotics, including clarithromycin, clindamycin, erythromycin, linezolid, streptogramins, tetracyclines, and tigecycline. This category consists mainly of bacteriostatic antibiotics that have prolonged PAEs. Some of these agents have been classified elsewhere as time-dependent; however, because of the presence of PAE, they also have concentration-dependent features. Efficacy of this group is determined by the 24-hour AUC to MIC ratio.

AUC:MIC ratio