EXPERIMENTAL STUDIES ON THE CHEMO-PROPHYLAXIS FOR PNEUMOCYSTIS CARINII PNEUMONIA WITH INTERMITTENT ADMINISTRATION OF TRIMETHOPRIM-SULFAMETHOXAZOLE AND PYRIMETHAMINE-SULFAMONOMETHOXINE

Chemoprophylaxis for Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole (TMPSMZ) has recently been widely applied in the clinical field since Hughes et al. (1977) established a regimen, which indicated daily administration of the drug for several months or sometimes over a year. In order to avoid the adverse effect, search for a minimum-effective dose or more convenient way of administration hasbeen desired. The present paper describes the chemoprophylactic effect of P. carinii pneumonia by means of intermittent administrations of TMP-SMZ and pyrimethamine-sulfamonomethoxine (PRM-SMM) in immunosuppressed rats. The results are summarized as follows : Group A. Twenty-nine out of 30 control rats which were not given prophylactic drug but given cortisone acetate showed severe P. carinii pneumonia.Group B. In a group of prophylactic regimen as PRM 15 mg/kg-SMM 300 mg/kg, once a week, 3 out of 21 rats showed light infection with P. carinii.Group C. In a group of TMP 100 mg/kg-SMZ 500 mg/kg administration, once a week, 5 out of 10 rats were moderately infected with P. carinii. The prophylactic effect seemed not enough by this procedure.Group D. All of 12 rats which received TMP 200 mg/kg-SMZ 1, 000 mg/kg (twice as much as Group C), once a week, showed negative for P. carinii.Group E. All of 21 rats which received TMP 100 mg/kg-SMZ 500 mg/kg, twice a week (2 consecutive days), were negative for P. carinii.Group F. All of 22 rats which received TMP 100 mg/kg-SMZ 500 mg/kg, twice a week (3-4 days interval), were also negative for P. carinii.From the results mentioned above, it can be said that intermittent prophylactic regimens in Group D, E and F showed satisfactory effect for preventing the onset of P. carinii pneumonia. Among those, the methodused in Group F seems to be most applicable in the clinical field, considering the side effects and in practical point of view.