Clinically used antimicrobial drugs against experimental pneumocystosis, singly and in combination: analysis of drug interactions and efficacies.
AUTOR(ES)
Walzer, P D
RESUMO
We analyzed single drugs and combinations of drugs used clinically in the treatment of opportunistic infections and other conditions for their activities against Pneumocystis carinii pneumonia in immunosuppressed rats. When they were used alone, atovaquone, rifabutin, and dapsone were more active than clarithromycin or trimethoprim. Drug combinations were evaluated for synergistic activity by an analysis of variance model for two-way factorial experiments and a response surface model. Atovaquone combined with trimethoprim trimethoprim and some combinations of dapsone and clarithromycin was synergistic; however, the activities of combinations of atovaquone and rifabutin, atovaquone and clarithromycin, and atovaquone and dapsone were simply additive. Lovastatin, which inhibits 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive whether it was used alone or in combination with other agents. None of the synergistic drug combinations was as effective as trimethoprim-sulfamethoxazole. We conclude that the rat model can be used to test combinations of anti-P. carinii agents for synergistic activity by well-established statistical techniques. While some combinations of clinically used antimicrobial drugs have enhanced anti-P. carinii activity, further studies are needed before clinical trials can be contemplated.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=163696Documentos Relacionados
- In Vitro Activities of Polycationic Peptides Alone and in Combination with Clinically Used Antimicrobial Agents against Rhodococcus equi
- In Vitro Activities of Membrane-Active Peptides Alone and in Combination with Clinically Used Antimicrobial Agents against Stenotrophomonas maltophilia
- Inhibitory and bactericidal activities of levofloxacin, ofloxacin, erythromycin, and rifampin used singly and in combination against Legionella pneumophila.
- Susceptibility of Pseudomonas maltophilia to antimicrobial agents, singly and in combination.
- In vitro activity of moxalactam and mecillinam, singly and in combination, against multi-drug-resistant Enterobacteriaceae and Pseudomonas species.