ACTIVITY OF TOPOISOMERASE INHIBITORS AGAINST PNEUMOCYSTIS-CARINII IN-VITRO AND IN AN INOCULATED MOUSE MODEL

Five topoisomerase II inhibitors (amsacrine [m-AMSA], two epipodophyllotoxins, and two quinolones) and the alkaloid camptothecin (a topoisomerase I inhibitor) were evaluated to assess their activities against Pneumocystis carinii. In vitro, both etoposide (VP-16) and teniposide (VM-26) at 1 mug/ml suppressed P. carinii growth. Amsacrine was toxic to P. carinii and to the feeder cells in vitro. Camptothecin suppressed the growth of P. carinii in vitro only at 100 mug/ml. Studies in immunosuppressed mice demonstrated the efficacy of teniposide against P. carinii pneumonia, but successful administration of teniposide was schedule dependent with significant toxicity at therapeutic dosages.