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 microgram/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 micrograms/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.
Infectious Disease Unit, Massachusetts General Hospital, Boston.
J A
JA
Fishman
S F
SF
Queener
R S
RS
Roth
M S
MS
Bartlett
D000818:Animals; D004195:Disease Models, Animal; D016576:Fleroxacin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011010:Pneumocystis / Q000187:drug effects* / Q000201:enzymology*; D016720:Pneumocystis Infections / Q000188:drug therapy*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D013713:Teniposide / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
D059005:Topoisomerase II Inhibitors; D013713:Teniposide; D016576:Fleroxacin