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.
Fishman
J A
JA
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Queener
S F
SF
Roth
R S
RS
Bartlett
M S
MS
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