Comparison of antibiotic dosage regimens using pharmacokinetic and microbiologic factors

A pharmacokinetic meta-analysis was performed for 33 antibiotics used in treating infections caused by microorganisms for which the antibiotics are considered to be agents of first choice or primary alternatives. The pharmacokinetic indices assessed were the following components of the steady-state blood concentration-time profile: the magnitude of the peak antibiotic serum concentration at steady state compared with the minimum inhibitory concentration (CSSmax/MIC) and the intensity index, a dimensionless term that reflects the contribution of the peak serum antibiotic concentration and the duration that this concentration is above the MIC. Substantial differences in CSSmax/MIC and intensity-index values were observed among antibiotics within an antibiotic class for individual microorganisms and for groups of microorganisms. Piperacillin, amikacin, and tetracycline showed the best mean performances of the ureido penicillins, aminoglycosides, and tetracyclines, respectively. For the cephalosporins, cefadroxil displayed the highest mean values of the first-generation cephalosporins; cefuroxime and cefotetan showed the greatest measures for the second-generation agents; and all third-generation cephalosporins demonstrated very high mean performance indices. Meta-analysis of pharmacokinetic performance factors is a useful technique for making intergroup and intragroup comparisons of antibiotics.