ACTIVITY OF TERBINAFINE AGAINST PNEUMOCYSTIS-CARINII IN-VITRO AND ITSEFFICACY IN THE TREATMENT OF EXPERIMENTAL PNEUMONIA

The antiprotozoan and antifungal agent, the terbinafine, was investiga ted for its potential activity against Pneumocystis carinii infection of the A549 cell line culture and on immunosuppressed Sprague Dawley r ats in comparison with trimethoprim-sulphamethoxazole and pentamidine isethionate. Terbinafine suppressed P. carinii growth at doses up to 3 g/L within 24 h and it was able to inhibit cyst forms at 60 h post in oculation. With respect to trimethoprim-sulphamethoxazole raze le and pentamidine isethionate P. carinii organisms decreased at the same tim e interval but cyst form elimination was less apparent than with terbi nafine. The results of the in-vitro culture were consistent with the i n-vivo observations. Of the 3 groups of rats tested, the occurrence of P. carinii pneumonia was documented in 18 (60%) of the control rats ( group 3) which showed a high degree of P. carinii burden and a marked weight loss with respect to the beginning of the experiment. Among ter binafine treated rats (group 1), P. carinii pneumonia was present in o ne rat (3.3%), while no P. carinii infection occurred in the pentamidi ne isethionate and in trimethoprim-sulphamethoxazole treatment rat gro ups (group 2). All the agents investigated showed no particular signs of toxicity. These preliminary results suggest further explorations of the terbinafine in clinical trials for treatment and prophylaxis of P . carinii pneumonia.