Efficacy of Trimethoprim and Sulfamethoxazole in the Prevention and Treatment of
            <i>Pneumocystis carinii</i>
            Pneumonitis

Hughes, Walter T.; McNabb, Paul C.; Μακρής, Θωμάς; Feldman, Sandor

doi:10.1128/aac.5.3.289

Cited by 207 publications

(110 citation statements)

References 11 publications

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“…The compounds were well tolerated by the animals and no gross toxicity was observed. Although the efficacy of these compounds against P. carinii has not been demonstrated in humans, it is encouraging that drugs currently used to treat P. carinji pneumonia, such as pentamidine and TMP/SMZ, are effective in the rat model (15,28). All previous treatments for P. carinji pneumonia have been limited by the lack of specificity, resulting in adverse reactions in the patient.…”

Section: Resultsmentioning

confidence: 99%

“…L-671,329 was used at a dose of 10 mg/kg and TMP and SMZ were used at doses of 0.2 and 1 g/liter, respectively. *Total cysts were determined by microscopic examination of 50 fields (x1000) of homogenized lung tissue on slides fixed with ether/sulfuric acid and stained with toluidine blue (15). tTotal nuclei were determined from duplicate slides stained with Diff-Quick.…”

Section: Resultsmentioning

confidence: 99%

“…L-671,329 is a natural product, which is a member of the echinocandin family, and was produced and isolated at Merck Sharp & Dohme Research Laboratories as described (12,13 (15), or left untreated for 14 days. Immunosuppression was continued during this period.…”

Section: Methodsmentioning

confidence: 99%

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Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Schmatz

Romancheck

Pittarelli

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

153

102

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Pneumocystis carini pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease. Recent evidence has suggested that P. carinn is related to fungi and that the wall ofthe cyst form contains 1,3-13-glucan as a major constituent. Based on this, several proposed 1,3-f3-glucan synthesis inhibitors were evaluated for their ability to control P. carinu pneumonia in vivo. Compounds from two classes of 1,3-13-glucan synthesis inhibitors, the echinocandins and papulacandins, were found to be effective against P. carinii.Pneumocystis carinii pneumonia is the most prevalent opportunistic infection and a frequent cause of death in AIDS

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Schmatz

Romancheck

Pittarelli

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

153

102

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“…Ϫ/Ϫ mice received sulfamethoxazole and trimethoprim (GensiaSicor Pharmaceuticals, Irvine, CA) treated water throughout the study to prevent opportunistic infection by Pneumocystis carinii (28).…”

Section: Micementioning

confidence: 99%

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

Kim

Flaño

Woodland

et al. 2002

The Journal of Immunology

127

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The human γ-herpesviruses, EBV and Kaposi’s sarcoma-associated herpesvirus, establish life-long latency and can reactivate in immunocompromised individuals. T cells play an important role in controlling persistent EBV infection, whereas a role for humoral immunity is less clear. The murine γ-herpesvirus-68 has biological and structural similarities to the human γ-herpesviruses, and provides an important in vivo experimental model for dissecting mechanisms of immune control. In the current studies, CD28−/− mice were used to address the role of Abs in control of persistent murine γ-herpesvirus-68 infection. Lytic infection was controlled in the lungs of CD28−/− mice, and latency was maintained in B cells at normal frequencies. Although class-switched virus-specific Abs were initially generated in the absence of germinal centers, titers and viral neutralizing activity rapidly waned. T cell depletion in CD28−/− mice with compromised Ab responses, but not in control mice with intact Ab responses, resulted in significant recrudescence from latency, both in the spleen and the lung. Recrudescence could be prevented by passive transfer of immune serum. These data directly demonstrate an important contribution of humoral immunity to control of γ-herpesvirus latency, and have significant implications for clinical intervention.

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“…The usual in-vivo model for experimental P. carinii research is the dexamethasone immunosuppressed rat, which relies on chemical immunosuppression to allow either the growth of endogenous P. carinii (Hughes et al, 1974;Kovacs et al, 1988;Masur et al, 1989;Davey & Masur, 1990), or exogenous P. carinii following intratracheal infection (Bartlett et al, 1990;Boylan & Current, 1992). Cortisone-immunosuppressed mice have also been used (Walzer, Powell & Yoneda, 1979a;Powles et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy

Kunz¹,

Junker²,

Blaser³

et al. 1995

J Antimicrob Chemother

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The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/ sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/ sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

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

Cited by 207 publications

References 11 publications

Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy

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