In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62,993), and A-56268) on Toxoplasma gondii

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Antimicrob. Agents Chemother.; (United States)

DOI:https://doi.org/10.1128/AAC.32.4.524· OSTI ID:6840945

Chang, H R; Pechere, J C

The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with (/sup 3/H)uracil, which is incorporated by the parasite but not the host cell. The 50% inhibitory concentrations (IC50s) and 95% confidence limits were calculated at 54 (38 to 73), 140 (98 to 201), 147 (101 to 214), and 246 (187 to 325) micron for roxithromycin, azithromycin (CP-62,993), A-56268, and spiramycin, respectively. Inhibition of Toxoplasma growth was confirmed by microscopic examination of the infected macrophages after treatment with roxithromycin. Compared with untreated controls, roxithromycin concentrations near the IC50s decreased the number of infected cells, the number of tachyzoites per vacuole, and the number of cells containing rosettes (i.e., clusters of more than eight tachyzoites). After treatment with the four macrolides, tachyzoites were released from the macrophages and subcultured in HeLa cells, which are nonprofessional phagocytes, to assess the viability of the remaining parasites. This showed that the macrolides at concentrations corresponding to four times their 90% inhibitory concentrations (IC90s) had no significant killing effect. At 8 times the IC90, roxithromycin showed an incomplete killing effect, similar to that of the combination of pyrimethamine (0.41 microM)-sulfadiazine (99.42 microM). All macrolides tested showed inhibitory effects against intracellular T. gondii, but amounts of azithromycin and A-56268 corresponding to the IC90 appeared to be toxic against the host macrophages, which might have had nonspecific activity against Toxoplasma metabolism.

• Research Organization: Centre Medical Universitaire (Switzerland)
• OSTI ID: 6840945
• Journal Information: Antimicrob. Agents Chemother.; (United States), Journal Name: Antimicrob. Agents Chemother.; (United States) Vol. 32:4; ISSN AMACC
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AZINES
BIOLOGICAL EFFECTS
CONNECTIVE TISSUE CELLS
DRUGS
ERYTHROMYCIN
GROWTH
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MACROPHAGES
MAMMALS
MICE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
PHAGOCYTES
PYRIMIDINES
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URACILS
VERTEBRATES
VIABILITY