cefmenoxime and Endocarditis--Bacterial

We studied the effect of a nonsteroidal anti-inflammatory drug, diclofenac, in rabbits on the kinetics of three cephalosporins: cefotiam, cefmenoxime and ceftriaxone, and compared the antibacterial effect of these antibiotics, given alone or with diclofenac, in experimental endocarditis. Diclofenac significantly increased (P less than .05) the area under the curve in tissue-cage fluid of ceftriaxone and cefotiam-treated animals, and the terminal half-life of ceftriaxone in their sera (3.45 +/- 0.4 vs. 2.8 +/- 0.5 hr). Diclofenac reduced urinary excretion of cefotiam only. Cefmenoxime pharmacokinetics remained unchanged by diclofenac. The alteration of ceftriaxone kinetics appeared to be due to nonrenal mechanisms and could suggest reduction of biliary excretion. In Escherichia coli endocarditis, diclofenac enhanced the concentration (P less than .05) of cefotiam (23 +/- 16 vs. 8.9 +/- 5 micrograms/g) and ceftriaxone (13.2 +/- 3 vs. 8.5 +/- 4 micrograms/g) in infected vegetations, but not that of cefmenoxime. The antibacterial effect of ceftriaxone increased with diclofenac (5.5 +/- 1 vs. 7.2 +/- 1 log10 colony forming unit/g of vegetation). In vitro, neither protein binding to rabbit serum proteins nor intrinsic activity on the E. coli strain of each antibiotic was modified by diclofenac. These results suggest that anti-inflammatory drugs could increase antibiotic efficacy by altering their pharmacokinetics. The renal and nonrenal site of interaction may be involved for drugs belonging to the same class. Results obtained in tissue-cage fluid were predictive of the interference at the infected site.

Topics: Animals; Cefmenoxime; Cefotaxime; Cefotiam; Ceftriaxone; Diclofenac; Drug Synergism; Endocarditis, Bacterial; Escherichia coli Infections; Injections, Intramuscular; Microbial Sensitivity Tests; Rabbits

To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Topics: Animals; Cefmenoxime; Cefotaxime; Cefotiam; Ceftriaxone; Drug Evaluation, Preclinical; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Kinetics; Rabbits

Antistaphylococcal activity of newer beta-lactam antibiotics, cefmenoxime, cefotaxime and latamoxef was compared with that of the more conventional antistaphylococcal agents, nafcillin, cefazolin and vancomycin. 53 strains of Staphylococcus aureus, 40 from patients with endocarditis and 13 from patients with bacteremia from other causes were tested in vitro against each antibiotic using agar dilution methods. Minimal concentration of antibiotic to inhibit 90% of strains tested was 2 micrograms/ml for cefmenoxime and cefotaxime, 8 micrograms/ml for latamoxef and only 0.5 microgram/ml for nafcillin, cefazolin and vancomycin. The newer beta-lactam antibiotics may not be preferred to nafcillin, cefazolin or vancomycin in the treatment of serious staphylococcal infections.

Topics: Anti-Bacterial Agents; Cefazolin; Cefmenoxime; Cefotaxime; Endocarditis, Bacterial; Humans; Microbial Sensitivity Tests; Moxalactam; Nafcillin; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Antistaphylococcal activity of three beta-lactam antibiotics, i.e. cefmenoxime, cefotaxime and latamoxef (moxalactam) was compared with that of nafcillin by studying cure rates of aortic valvular endocarditis caused by one of three clinical isolates of Staphylococcus aureus in New Zealand white male rabbits. The animals were randomly allocated to a control and four antibiotic treatment groups. Each animal except the controls received 60 mg/kg of one antibiotic intramuscularly twice daily for two weeks, beginning 24 h after induction of endocarditis. The aortic valve was sterilized in 11 of 15 (73%) animals treated with cefmenoxime, nine of 13 (69%) treated with cefotaxime, 11 of 13 (85%) treated with latamoxef and 12 of 15 (80%) treated with nafcillin. All nine animals in the control group developed aortic valvular vegetations with an average of 2.4 X 10(9) cfu/g. The differences in sterility rates resulting from treatment with the four antibiotics were not statistically significant (P greater than 0.70).

Topics: Animals; Cefmenoxime; Cefotaxime; Endocarditis, Bacterial; Humans; Male; Microbial Sensitivity Tests; Moxalactam; Nafcillin; Rabbits; Staphylococcal Infections