The Effect of Two Chlorinated Lincomycin Analogues Against Acute Toxoplasmosis in Mice

McMaster, Philip R. B.; Powers, Kendall G.; Finerty, John F.; Lunde, Milford N.

doi:10.4269/ajtmh.1973.22.14

Cited by 55 publications

(26 citation statements)

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“…As alternative treatments, the experimental in vitro and in vivo activities of some new macrolides have been assessed (1,5,(7)(8)(9), but their efficacies in human toxoplasmosis, however, remain to be confirmed in clinical trials. Clindamycin has been shown to have activity in animal models of toxoplasmosis (2,32,41), and its use as an alternative drug in the treatment of patients who do not tolerate sulfonamides has been reported recently (12).…”

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In vitro and in vivo effects of doxycycline on Toxoplasma gondii

Chang

Comte

Péchère

1990

Antimicrob Agents Chemother

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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 ,Ig/ml (95% confidence limits, 5.07 to 8.06 ,ug/ml); the concentration of doxycycline that inhibited 90% of the radioactive uptake was 14 pg/ml. Tetracycline was ineffective up to 40 ,ug/ml. Furthermore, microscopic examination of the infected macrophages after treatment with doxycycline confirmed the inhibition of intracellular growth of T. gondui. Mice acutely infected by the intraperitoneal route with 5 x 103 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 105 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.Infection with Toxoplasma gondii is a potential hazard for immunocompromised patients, such as those suffering from the acquired immune deficiency syndrome (AIDS) (30). Currently, the treatment of choice for toxoplasmosis is the synergistic combination of pyrimethamine with sulfonamides (20,29,43). The treatment of patients with AIDS suffering from toxoplasmic encephalitis with this combination entails a significant mortality rate, usually associated with relapse after withdrawal of therapy for reasons of toxicity, mainly because of the sulfonamide component of the combination (27,30). Moreover, it has been proposed that patients with AIDS suffering from toxoplasmic encephalitis should be maintained on a chronic suppressive (clinical prophylactic) regimen to avoid relapses (23). Thus, the development of effective and safer compounds for treating this disease is critically needed. As alternative treatments, the experimental in vitro and in vivo activities of some new macrolides have been assessed (1,5,(7)(8)(9), but their efficacies in human toxoplasmosis, however, remain to be confirmed in clinical trials. Clindamycin has been shown to have activity in animal models of toxoplasmosis (2, 32, 41), and its use as an alternative drug in the treatment of patients who do not tolerate sulfonamides has been reported recently (12).Among the other possible therapies, the antitoxoplasmic activities of tetracyclines have been studied in animal models. The results of those studies with tetracycl...

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In vitro and in vivo effects of doxycycline on Toxoplasma gondii

Chang

Comte

Péchère

1990

Antimicrob Agents Chemother

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“…Clindamycin has been demonstrated to be effective against acute toxoplasmosis (12) and malaria (10) in animals. This drug acts as an inhibitor of protein synthesis.…”

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Efficacy of Trimethoprim and Sulfamethoxazole in the Prevention and Treatment of Pneumocystis carinii Pneumonitis

Hughes

McNabb

Μακρής

et al. 1974

Antimicrob Agents Chemother

207

105

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A combination of trimethoprim and sulfamethoxazole was effective in the prevention and treatment of Pneumocystis carinii pneumonitis in cortisonetreated rats. Although all of 15 untreated rats died with P. carinii pneumonitis, none of 15 given trimethoprim-sulfamethoxazole prophylactically acquired the infection. After P. carinii pneumonitis was established, 9 of 14 rats recovered after treatment with trimethoprim-sulfamethoxazole compared with only 2 of 14 treated with pentamidine isethionate. Rifampin and clindamycin, separately or in combination with pentamidine, were ineffective in the prevention and treatment of P. carinii infection.

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“…Clindamycin was enthusiastically embraced as part of treatment regimes in the 1980s (Tabbara & O'Connor 1980) since it appeared that the drug was concentrated in ocular tissue and might penetrate tissue cyst walls (Tabbara & O'Connor 1975). In experimental models, the drug reduced the number of tissue cysts (McMaster et al 1973) but subsequent clinical experience showed no effect on disease recurrence (Lakhanpal et al 1983). In the 1990s, azithromycin (Rothova et al 1998) and atovaquone (Pearson et al 1999) were both introduced but have not gained widespread acceptance.…”

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confidence: 99%