Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.
Pneumocystis carinii pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease. Recent evidence has suggested that P. carinii is related to fungi and that the wall of the cyst form contains 1,3-beta-glucan as a major constituent. Based on this, several proposed 1,3-beta-glucan synthesis inhibitors were evaluated for their ability to control P. carinii pneumonia in vivo. Compounds from two classes of 1,3-beta-glucan synthesis inhibitors, the echinocandins and papulacandins, were found to be effective against P. carinii.
Department of Biochemical Parasitology, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
D M
DM
Schmatz
M A
MA
Romancheck
L A
LA
Pittarelli
R E
RE
Schwartz
R A
RA
Fromtling
K H
KH
Nollstadt
F L
FL
Vanmiddlesworth
K E
KE
Wilson
M J
MJ
Turner
D000818:Animals; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004195:Disease Models, Animal; D054714:Echinocandins; D005936:Glucans / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D011010:Pneumocystis / Q000187:drug effects / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000473:pathology; D011714:Pyrans / Q000506:poisoning / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013420:Sulfamethoxazole / Q000494:pharmacology / Q000627:therapeutic use; D014295:Trimethoprim / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005936:Glucans; D010455:Peptides; D010456:Peptides, Cyclic; D011714:Pyrans; C058995:pneumocandin A(0); C065110:L 687781; D014295:Trimethoprim; D013420:Sulfamethoxazole