minocycline and Cryptosporidiosis

The anticryptosporidial activity of four macrolides alone and in combination with other antimicrobial agents was investigated against ten clinical isolates of Cryptosporidium parvum recovered from stools of AIDS patients. The susceptibility tests were performed by inoculation of the protozoa on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of azithromycin, clarithromycin, roxithromycin, spiramycin, alone or in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine. Most of the agents had an inhibitory effect on parasite growth, but only at high concentrations. No agent was able to inhibit parasite growth completely, even at the highest concentrations used. The more effective agents, azithromycin, clarithromycin, roxithromycin, minocycline and pyrimethamine, produced no more than a 13.1-27.8% reduction in oocyst count and no more than a 15.1-35.7% in schizont count. Positive interaction was clearly demonstrated when macrolides were tested in combination with minocycline or pyrimethamine.

Topics: Acquired Immunodeficiency Syndrome; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Artemisinins; Atovaquone; Cryptosporidiosis; Cryptosporidium parvum; Dapsone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Lactones; Macrolides; Minocycline; Naphthoquinones; Pyrimethamine; Sesquiterpenes

Glycoside antibiotics including the macrolide antibiotics azithromycin, clarithromycin, and erythromycin and the aminoglycoside paromomycin were administered alone or combined with doxycycline, minocycline, or tetracycline to neonatal BALB/c mice experimentally infected with Cryptosporidium parvum. Glycosides at 100 or 200 mg/kg of body weight and tetracyclines at 50 mg/kg of body weight were dissolved in dimethylsulfoxide (DMSO), which was then diluted with phosphate-buffered saline (PBS) and given orally by gavage. Drugs were administered at 0, 24, 48, and 72 hr postinfection (PI) for prophylaxis. Histologic sections of ileum, cecum, and colon from tissues fixed at 96 hr PI were examined microscopically to determine the number of developing parasites and assign a quantitative score based on infectivity. All groups that received glycosides had significantly (P < 0.01) lower scores than controls that received only DMSO/PBS. A range in efficacy was apparent. None or extremely few parasites were found in paromomycin- and azithromycin-treated groups, whereas few to moderate numbers of parasites were found in erythromycin- and clarithromycin-treated groups. The addition of tetracyclines did not consistently result in significantly lower scores.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cryptosporidiosis; Cryptosporidium parvum; Disease Models, Animal; Doxycycline; Drug Synergism; Drug Therapy, Combination; Erythromycin; Mice; Mice, Inbred BALB C; Minocycline; Paromomycin; Tetracyclines