Experimental studies on the chemoprophylaxis for Pneumocystis carinii pneumonia with intermittent administration of trimethoprim-sulfamethoxazole and pyrimethamine-sulfamonomethoxine.
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Chemoprophylaxis for <I>Pneumocystis carinii</I> pneumonia with trimethoprim-sulfamethoxazole (TMPSMZ) has recently been widely applied in the clinical field since Hughes <I>et al</I>. (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 <I>P. carinii</I> pneumonia by means of intermittent administrations of TMP-SMZ and pyrimethamine-sulfamonomethoxine (PRM-SMM) in immunosuppressed rats. The results are summarized as follows : <BR>Group A. Twenty-nine out of 30 control rats which were not given prophylactic drug but given cortisone acetate showed severe <I>P. carinii</I> pneumonia.<BR>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 <I>P. carinii</I>.<BR>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 <I>P. carinii</I>. The prophylactic effect seemed not enough by this procedure.<BR>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 <I>P. carinii</I>.<BR>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 <I>P. carinii</I>.<BR>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 <I>P. carinii</I>.<BR>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 <I>P. carinii</I> 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.
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