The therapeutic efficacies of
cefadroxil and
cephalexin were compared in a Streptococcus pyogenes-induced lung
infection in rats. Although MICs, rates of in vitro killing in rat serum, and
antibiotic serum levels after
oral administration were similar for both drugs,
cefadroxil was about eight times more effective than
cephalexin in reducing the number of viable streptococci at the site of
infection. This excellent in vivo bactericidal activity of
cefadroxil in lung tissue and bronchial secretions was reflected in the 50% protective dose (PD50) after single or multiple oral treatments. A single treatment given 24 h after
infection resulted in a PD50 of 2.8 mg of
cefadroxil per kg, compared with 21 mg of
cephalexin per kg. When treatment was administered three times, at 24, 27, and 30 h postinfection, the PD50s of
cefadroxil and
cephalexin were 0.7 and 8.0 mg/kg, respectively. In infected animals, treated 24 h postinfection, the area under the lung tissue concentration versus time curve for
cefadroxil was significantly greater than that of
cephalexin. This difference in pharmacokinetic behavior may account, at least in part, for the superior therapeutic results obtained with
cefadroxil in this experimental pulmonary
infection.