Drug Evaluation of Concurrent Pneumocystis Carinii, Toxoplasma Gondii, and Mycobacterium Avium Complex Infections in a Rat Model

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1998 May 21

PMID 9593128

Citations 3

Authors

F Chau

G Bertrand

L Garry

F Derouin

P M Girard

Affiliations

Soon will be listed here.

Abstract

We present a new experimental model for the simultaneous evaluation of the activities of drugs against Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium complex infections. Rats latently infected with P. carinii were challenged with the MO-1 strain of M. avium and then immunosuppressed with corticosteroids for 7 weeks. At week 5 the RH strain of T. gondii was intraperitoneally injected. Organs were examined for the three pathogens after death or killing of the animals at week 7. Without treatment, rats challenged with T. gondii died with pulmonary P. carinii infection and disseminated T. gondii and M. avium infections. In order to assess the value of the model for evaluation of the activities of drugs, we administered by oral gavage for 7 weeks drugs or combinations of drugs selected for their individual efficacies against at least one pathogen. We found that clarithromycin with sulfamethoxazole, clarithromycin with atovaquone, roxithromycin with sulfamethoxazole or dapsone, and rifabutin with atovaquone were effective against the three infections, whereas PS-15 with dapsone and trimethoprim with sulfamethoxazole were active against Toxoplasma and Pneumocystis infections only. This triple-infection rat model offers a new tool for the simultaneous evaluation of the activities of drugs against three of the major opportunistic infections occurring in immunosuppressed individuals.

Citing Articles

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice.

Dunay I, Gajurel K, Dhakal R, Liesenfeld O, Montoya J Clin Microbiol Rev. 2018; 31(4).

PMID: 30209035 PMC: 6148195. DOI: 10.1128/CMR.00057-17.

Atovaquone maintenance therapy prevents reactivation of toxoplasmic encephalitis in a murine model of reactivated toxoplasmosis.

Dunay I, Heimesaat M, Bushrab F, Muller R, Stocker H, Arasteh K Antimicrob Agents Chemother. 2004; 48(12):4848-54.

PMID: 15561866 PMC: 529229. DOI: 10.1128/AAC.48.12.4848-4854.2004.

Prediction of quinolone activity against Mycobacterium avium by molecular topology and virtual computational screening.

Gozalbes R, Garcia-Domenech R, Galvez J, Girard P, Doucet J, Derouin F Antimicrob Agents Chemother. 2000; 44(10):2764-70.

PMID: 10991858 PMC: 90149. DOI: 10.1128/AAC.44.10.2764-2770.2000.

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