Efficacy of rifampicin in experimental Bacteroides fragilis and Pseudomonas aeruginosa mixed infections.

Experimental intraabdominal abscesses were produced in mice by intraperitoneal injection of Bacteroides fragilis and Pseudomonas aeruginosa. The therapeutic efficacy of rifampicin and cefsulodin alone, and in combination was investigated in this in-vivo experimental mixed intraabdominal abscess model. Treatment with rifampicin at 10, and 25 mg/kg or cefsulodin at 50, and 100 mg/kg singly or in combinations prevented mortality as compared to 68% mortality rate occurring in the untreated mice. Rifampicin, at 25 mg/kg dose, was very effective in preventing abscess formation and produced bacterial eradication. It prevented abscess formation in 80% of the mice and eradicated both Bacteroides and Pseudomonas in 100% and 75% of the abscesses of the mice. Cefsulodin failed to reduce the incidence of abscess formation, and to eradicate Bact. fragilis from the abscesses, although it significantly decreased Ps. aeruginosa in the abscesses. The combination of rifampicin at 10 mg/kg and cefsulodin at 100 mg/kg was more effective than either of the antibiotics alone and was as effective as rifampicin alone at 25 mg/kg levels. This combination was bactericidal against both organisms in the infected mice.

Therapeutic efficacy and pharmacokinetic properties of rifampicin in a Bacteroides fragilis intra-abdominal abscess.

The efficacy of rifampicin in treating a Bacteroides fragilis infection was investigated and compared to clindamycin and metronidazole in an experimental model of intra-abdominal abscess in mice. Rifampicin, when given subcutaneously, showed activity superior to that of clindamycin in reducing the incidence of abscess formation as well as the number of Bacteroides organisms recovered from the abscess, and rifampicin was comparable in efficacy to metronidazole when given orally at the same dose level. The comparative pharmacokinetic properties of rifampicin and clindamycin demonstrated that the peak serum and abscess levels reached with rifampicin were significantly higher than those of clindamycin. The half-life of rifampicin in serum and in the abscess was longer than that of clindamycin.

Synergistic activity of cefsulodin combined with cefoxitin and sulbactam against Bacteroides species.

The in-vitro activity of cefsulodin combined with sulbactam, cefoxitin or cefotaxime was investigated against 32 strains of beta-lactamase-producing Bacteroides species. Synergy of cefsulodin-sulbactam or cefsulodin-cefoxitin could be demonstrated against 30 of 32 and 32 of 32 strains tested at the concentrations readily achievable in serum. In the presence of 1 mg/l of sulbactam or cefoxitin, more than 90% of the Bacteroides isolated were inhibited by 32 mg/l of cefsulodin. The inhibitory activity of cefsulodin-sulbactam or cefsulodin-cefoxitin combinations was bactericidal against Bact. fragilis and Bact. vulgatus. In contrast, no synergistic inhibitory or bactericidal activities can be observed by the cefsoludin-cefotaxime combination. Both sulbactam and cefoxitin were potent inhibitors of beta-lactamases produced by Bact. fragilis and Bact. melaninogenicus suggesting that this inhibitory activity might be one of the factors contributing to the synergistic combinations.

Antimicrobial susceptibility, growth kinetic and pathogenicity of thymidine-requiring Streptococcus species.

18 strains of thymidine-requiring streptococcal mutants (thy-) were isolated from urines of patients with urinary tract infection treated with trimethoprim-sulfameth-oxazole (TMP-SMZ) or trimethoprim-sulfadiazine (TMP-SDZ). All thy- mutants were catalase- and beta-lactamase-negative, grew in the presence of bile and esculin, and required from 0.3 to greater than 1280 micrograms/ml of thymidine for normal growth. The antibiotic susceptibility of wild-type and thy- mutants to 21 antimicrobial agents tested were comparable except to trimethoprim (TMP), TMP-SMZ and TMP-SDZ. Ampicillin, penicillin G, erythromycin and rifampin were among the most active compounds tested. Growth kinetic studies with a Streptococcus faecalis thy- mutant in a synthetic basal medium without thymidine resulted in a decrease of 2-3 logarithmic units in viable cells after 24 h of incubation. The addition of thymidine to this thymidine-deprived culture prevented the thymineless death of the cells. In vivo, this thy- mutant was less virulent than the wild-type strain in producing kidney infection in mice.

Analysis of rifampin disk diffusion and stability in 7H10 agar.

Rifampin was incorporated into Middlebrook 7H10 medium either by adding an aliquot of the antibiotic into melted agar (final concentration 1.0 and 3.0 mug/ml) or by submerging a 5 or 15 mug of rifampin paper disk into 5 ml of melted agar contained in one quadrant of a Felson "X" plate. At intervals, plugs of agar were removed from the stored plates and assayed. Plates stored at 5 C for 28 days showed no loss of potency; at 37 C, the half-life of rifampin was 9 days. Stability of rifampin at these concentrations in 7H10 medium was independent of the method used for incorporation. Using the disk method, uniform rifampin concentrations of 0.75 mug/ml on day 5 for the 5-mug disk and 2.7 mug/ml on day 6 for the 15-mug disk were observed. Results indicated that the rifampin concentrations within the agar dilution and disk diffusion plates were equivalent at these times.

Antimicrobial effectiveness of Locacorten-Vioform cream in Secondary infections of common dermatoses.

In a double-blind study involving 430 patients, Locacorten (0.02%)-Vioform (3%) cream was found to be highly effective in the treatment of dermatological conditions complicated by secondary bacterial involvement. Themicrobiological conversion and clinical improvement in patients treated with Locacorten-Vioform combinations were markedly greater than those achieved in the groups medicated with (1) Vioform 3%, (2) Locacorten 0.02%, and (3) placebo cream. Staphylococcus aureus was the most prevalent organism isolated from the skin lesions. All strains were sensitive to Vioform, as compared to 62% found to be resistant to other antimicrobials.