Cefoperazone pharmacokinetics in normal subjects and patients with cirrhosis.

The pharmacokinetics of cefoperazone were studied and compared in six normal subjects and six patients with severe liver disease. All subjects received a 2-g intravenous infusion of cefoperazone over 15 min. Significantly different results were noted between normal subjects and patients with cirrhosis (range [mean]) for the following: peak serum concentrations (203 to 345 [239] versus 82 to 206 [141] micrograms/ml; P less than 0.01); serum beta half-lives (1.0 to 1.8 [1.5] versus 2.3 to 9.9 [4.5] h; P less than 0.05); renal excretion (17 to 27 [21] versus 32 to 60 [50]%; P less than 0.01); and apparent volumes of distribution at steady state (4.1 to 7.8 [6.3] versus 12.7 to 23.8 [15.9] liters/1.73 m2; P less than 0.01). Lower peak serum levels in the patients with cirrhosis were probably related to an increased apparent volume of distribution secondary to ascites and to decreased serum protein binding of cefoperazone. Longer beta half-lives in the patients with cirrhosis were probably secondary to both decreased hepatic excretion caused by severe liver disease and to increased apparent volume of distribution. However, the longest beta half-life among the patients with cirrhosis was in a subject with a serum creatinine level of 2.1 mg/dl. We conclude that, although mild to moderate impairment of cefoperazone excretion occurs in patients with hepatic disease, adjustment of dosage may be necessary only with concomitant renal insufficiency.

Effect of cimetidine and antacid on gastric microbial flora.

The effect of a standard regimen of cimetidine on the gastric flora of 20 male volunteers was studied in a double-blind manner and compared with the effects of a standard antacid regimen. Postprandial microbial titers in gastric aspirates were significantly higher at 4, 8, and 16 weeks of therapy in subjects taking antacids and at 4 weeks in subjects taking cimetidine when compared with their pretreatment titers. Although not significant, there was a tendency for fasting microbial titers to be higher in subjects receiving cimetidine as compared with pretreatment titers. The higher titers were primarily related to increases in survival of mouth flora (viridans streptococci and Neisseria spp.); Enterobacteriaceae and other nitrate-reducing organisms were unusual isolates. There was no significant difference in the total titers or types of organisms isolated when subjects taking cimetidine were compared with those taking antacid.

In vitro activity, efficacy, and pharmacology of moxalactam, a new beta-lactam antibiotic.

Moxalactam, a potent new beta-lactam antibiotic with a relatively wide spectrum of activity against facultative and anaerobic gram-negative bacilli, was evaluated in vitro and in 28 patients with a variety of severe infections with moxalactam-susceptible organisms (minimum inhibitory concentration less than or equal to 31 microgram/ml). Although therapy was successful in most of these patients, caution is suggested because of the development of resistance on therapy in one patient, persistence of Bacteroides fragilis endocarditis in another, and for certain organisms, a significant inoculum effect on the minimum inhibitory concentration and minimum bactericidal concentration of moxalactam.

Cefoperazone treatment of experimental endocarditis.

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.