Pharmacokinetic and microbiologic evaluation of dosage regimens for newer cephalosporins and penicillins.

A retrospective pharmacokinetic analysis was performed for eight newer cephalosporins and penicillins and one aminoglycoside used in treating 10 microorganisms for which the antibiotics are considered to be primary alternatives. The pharmacokinetic indices assessed were the three components of the steady-state temporal blood concentration profile: (1) the magnitude of the peak antibiotic blood level at steady state compared with the mininum inhibitory concentration (CSSmax/MIC), (2) the number of hours that the blood level is greater than the MIC during a 72-hour treatment period, and (3) the intensity index, which is a dimensionless term that reflects the contributions of both the peak serum level of the antibiotic and duration of this level above the MIC. Substantial differences were demonstrated in pharmacokinetic indices for dosage regimens used in treating specific microorganisms for which the antibiotics are considered the primary alternative agents. Moxalactam, cefoxitin, and piperacillin demonstrated the best pharmacokinetic performances for the third-generation cephalosporin, second-generation cephalosporin, and newer penicillin groups, respectively. The data suggest that some antibiotics, notably moxalactam and cefotaxime, may be effective at lower doses than commonly recommended, while others, like cefoperazone, cefamandole, and azlocillin, are probably often ineffective even at high doses.