The combination of
primaquine with
clindamycin is effective in both in vitro and in vivo models of
Pneumocystis infection.
Primaquine alone at concentrations from 10 to 300 micrograms/ml reduced the numbers of organisms in cultures to less than 7% of control. Significant inhibition was observed down to 0.1 microgram/ml.
Clindamycin at 5 micrograms/ml was ineffective alone. Combinations of
clindamycin and
primaquine in culture at various concentrations were effective, but there was no evidence of true synergy. In rats with established
Pneumocystis pneumonia,
clindamycin alone at 5 or 225 mg/kg was ineffective.
Primaquine alone at 0.5 or 2 mg/kg did not significantly affect the numbers of organisms remaining. The combination of 0.5 mg of
primaquine per kg and 225 mg of
clindamycin per kg was effective for
therapy, lowering the numbers of organisms in the lungs by about 90%. The combination of 2 mg of
primaquine per kg and 225 mg of
clindamycin per kg was more effective, lowering the numbers of organisms by almost 98%. In the in vivo prophylaxis model,
primaquine at 0.1 or 0.2 mg/kg did not prevent the development of
Pneumocystis pneumonia in immune-suppressed rats.
Clindamycin at 50 mg/kg had a modest effect alone, but at 5 mg/kg all animals became heavily infected. At 0.5 mg/kg,
primaquine alone reduced the severity of
infection, but seven of eight rats were still infected. In contrast, the combination of 5 mg of
clindamycin per kg and 0.5 mg of
primaquine per kg prevented
infection in 8 of 10 rats; 2 rats had minimal
infection. These studies suggest that the combination of
clindamycin and
primaquine should be tested in
therapy or prophylaxis of
Pneumocystis infections in humans.