The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics.
Pharmacokinetic-pharmacodynamic (PK/PD) surrogate indices (AUIC, AUC/MIC, C(max)/MIC, T>MIC) for measuring antibiotic efficacy are presented and reviewed. As clinical trials are not sufficiently sensitive to establish a dosage regimen which guarantees total bacteriological cure (Pollyanna phenomenon), PK/PD indexes have been proposed from in vitro, ex vivo, and in vivo infection models and subsequently validated in retrospective or prospective human clinical trials. The target value for time-dependent antibiotics (beta-lactams, macrolides) is a time above the MIC (T>MIC) of 50-80% of the dosage interval, while for concentration-dependent antibiotics (quinolones and aminoglycosides), the area under the inhibitory curve (AUIC, or more simply AUC/MIC of about 125h) is the best surrogate indicator of activity. Using the latter drugs, high concentrations achieved early during therapy are desirable to prevent the development of resistance. A C(max)/MIC ratio greater than 10-12 seems to be an appropriate target for aminoglycosides.
UMR INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse cedex 03, France. pl.toutain@envt.fr
P L
PL
Toutain
J R E
JR
del Castillo
A
A
Bousquet-Mélou
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000662:veterinary; D002986:Clinical Trials as Topic / Q000662:veterinary; D004334:Drug Administration Schedule / Q000662:veterinary; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents