Cefatrizine activity compared with that of other cephalosporins. (1/4)

Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 mug/ml. Cefatrizine inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella at concentrations below 12.5 mug/ml. Although cefatrizine was not hydrolyzed by many beta-lactamases, it did not inhibit a number of strains of Enterobacter, Serratia, or indole-positive Proteus. Cefatrizine was more active than cephalothin or cephalexin against E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella, and Shigella. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole.  (+info)

Human intravenous pharmacokinetics and absolute oral bioavailability of cefatrizine. (2/4)

Cefatrizine was administered intravenously and orally at dose levels of 250, 500, and 1,000 mg to normal male volunteers in a crossover study. Intravenous pharmacokinetics were dose linear over this range; mean peak plasma concentrations at the end of 30-min infusions were, respectively, 18, 37, and 75 micrograms/ml, total body clearance was 218 ml/min per 1.73 m2, renal clearance was 176 ml/min per 1.73 m2, and mean retention time in the body was 1.11 h. Cumulative urinary excretion of intact cefatrizine was 80% of the dose, and half-lives ranged from 1 to 1.4 h. Steady-state volume of distribution was 0.22 liters/kg. On oral administration, the absolute bioavailabilities of cefatrizine were 75% at 250 and 500 mg and 50% at 1,000 mg. The mean peak plasma concentrations and peak times were, respectively, 4.9, 8.6, and 10.2 micrograms/ml at 1.4, 1.6, and 2.0 h, mean residence times were 2.4, 2.6, and 3.1 h, and mean absorption times were 1.3, 1.6, and 1.9 h. Oral renal clearance and half-life values corresponded well to the intravenous values. Cumulative urinary excretion of intact cefatrizine (as percentage of dose) was 60 at 250 mg, 56 at 500 mg, and 42 at 1,000 mg. It is hypothesized that the lack of oral dose linearity between the 500- and 1,000-mg doses is due to a component of cefatrizine absorption by a saturable transport process. Relative absorption at the high dose would be sufficiently slow that an absorption "window" would be passed before maximum bioavailability could be attained. It is not expected that the observed bioavailability decrease at doses exceeding 500 mg will have any therapeutic significance, since clinical studies are establishing efficacy for a recommended unit dosage regimen of 500 mg.  (+info)

In vitro activities of five oral cephalosporins against aerobic pathogenic bacteria. (3/4)

Cefaclor (Lilly 99638) and cefatrizine (BL-S640, SK&F 70771) are orally absorbed, broad-spectrum semisynthetic cephalosporins. They were compared in vitro with cephalexin, cephaloglycin, and cepharadine against a variety of aerobic pathogenic bacteria by an agar dilution procedure. Cefaclor and cefatrizine were found to be similar or superior to cephalexin, cephaloglycin, and cephradine in terms of activity against gram-positive cocci other than enterococci. Only cefatrizine demonstrated any potentially useful activity against some susceptible isolates of enterococci. Cefaclor and cefatrizine also were highly active, equally or more so than the other oral cephalosporins, against several gram-negative species including Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. None of the cephalosporins were particularly active against Enterobacter cloacae. Both cefaclor and cefatrizine were active against Proteus mirabilis; cefatrizine was uniquely active against indolepositive Proteus species.  (+info)

In-vitro activity of 21 beta-lactam antibiotics against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. (4/4)

MICs of 21 beta-lactams were determined by agar dilution against 283 penicillin-susceptible (pen-S), 122 intermediate (pen-I) and 23 fully penicillin-resistant (pen-R) pneumococci. MICs of all beta-lactams increased with increasing MICs of penicillin. Clometocillin was the most active penicillin against pen-I or pen-R pneumococci. All oral cephalosporins except cefuroxime and cefpodoxime were less active than penicillin and none was satisfactory against pen-I or pen-R pneumococci. The parenteral third- and fourth-generation cephalosporins (except ceftazidime) were similar in activity to penicillin against pen-S isolates. Cefpirome showed the lowest mean MICs against pen-I and pen-R strains.  (+info)