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R Comte

Publications and source records attributed to R Comte.

6 recordsLinked to original sources
PubMed1994

Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis.

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Animals↗
PubMed1994

Activity of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii.

We examined the effect of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone, against Toxoplasma gondii. In vitro, the anti-T. gondii effects of epiroprim and dapsone were observed at nanogram-per-milliliter levels when a 72-h uracil assay and an infection rate of one parasite per 120 macrophages were used. In combination, these drugs exerted a synergistic effect that, however, was only parasitostatic. In a model of acute infection, mice were infected intraperitoneally with 10(4) parasites of the RH strain of T. gondii and were treated for 14 days by gavage (therapy divided into two daily dosages), starting 24 h after infection. Used alone, dapsone and epiroprim, each at a dose of 50 mg/kg of body weight per day, protected 10 and 0% of the mice, respectively. When these drugs were administered simultaneously, a 100% survival rate was observed. Pyrimethamine-sulfadiazine (4 and 250 mg/kg/day, respectively) protected 100% of the mice. A 3-week therapy of chronically infected mice with either epiroprim (50 mg/kg/day), dapsone (50 mg/kg/day), or pyrimethamine (15 mg/kg/day) reduced the numbers of T. gondii cysts and the inflammation in their brains. A combination of epiroprim and dapsone, both at 50 mg/kg/day, further reduced the number of brain cysts in comparison with the number after the corresponding monotherapies. Epiroprim may have a role in the prophylaxis or therapy of human toxoplasmosis, especially when combined with other drugs active against T. gondii, such as dapsone.

Animals↗
PubMed1991

Prevention of vascular graft infection by rifampin bonding to a gelatin-sealed Dacron graft.

This study examines the efficacy of rifampin bonding to a gelatin-sealed knitted Dacron graft to prevent perioperative bacteremic vascular graft infection. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 1 mg/ml saline solution of rifampin at 37 degrees C. Nineteen dogs had thoracoabdominal aortic bypass: seven (group I) received a rifampin treated graft; six (group II) received an untreated gelatin-coated graft; and six (group III) received an uncoated Dacron graft. Two days later bacteremic challenge was produced by rapid intravenous injection of 5 x 10(5) colony forming units of methicillin resistant Staphylococcus aureus. Grafts were harvested five days after this challenge and cut into 10 fragments, each submitted to bacterial counts. Results were expressed as CFU/cm2 of graft material. In group I, no graft was infected, whereas all grafts in groups II and III were infected (p less than 0.05). Median bacterial counts from the infected fragments (median +/- SD) were similar in groups II (2.5 x 10(5) CFU/cm2) and III (4 x 10(4) CFU/cm2). Blood cultures at time of sacrifice were negative in all dogs in group I and positive in five of six dogs in groups II and III. Cultures of liver, spleen, kidney, and lung specimens were always negative in group I and positive in 22 of 24 specimens in group II and 23 of 24 specimens in group III. Soaking a gelatin-sealed Dacron graft in rifampin solution evidently prevents early bacteremic graft infection and secondary foci of infection in this model.

Animals↗
PubMed1991

Activity of minocycline against Toxoplasma gondii infection in mice.

The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10(5) tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8.5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1.8 mg/l and 10 mg/l after 1 h, respectively, and showed an extended half-life.

Acute Disease↗
PubMed1990

In vitro and in vivo effects of doxycycline on Toxoplasma gondii.

We investigated the effects of doxycycline on Toxoplasma gondii infections in vitro and in vivo. Resident peritoneal macrophages were infected with the virulent RH strain of T. gondii and exposed to doxycycline at different concentrations. The antitoxoplasmic activity of doxycycline was first assessed with [3H]uracil, which is incorporated by the parasite but not the host cell. The concentration of doxycycline that inhibited 50% of the radioactive uptake was calculated to be 6.4 micrograms/ml (95% confidence limits, 5.07 to 8.06 micrograms/ml); the concentration of doxycycline that inhibited 90% of the radioactive uptake was 14 micrograms/ml. Tetracycline was ineffective up to 40 micrograms/ml. Furthermore, microscopic examination of the infected macrophages after treatment with doxycycline confirmed the inhibition of intracellular growth of T. gondii. Mice acutely infected by the intraperitoneal route with 5 x 10(3) tachyzoites of T. gondii were protected against death with a dose of 300 mg of doxycycline per kg (body weight) administered by the oral route for 10 days, starting 24 h after challenge. When mice were infected with 10(5) tachyzoites of T. gondii and treated 12 days starting 2 h after challenge, the protection and the cure rates were, respectively, 100 and 0% after doxycycline alone (300 mg/kg per day), 0 and 0% after pyrimethamine alone (12.5 mg/kg per day), and 100 and 60% after the combination of these two drugs at the same dosages given above. These results suggest that doxycycline may prove to be useful in the treatment of toxoplasmic infections.

Animals↗