Clindamycin Activity Against Chloroquine-Resistant Plasmodium falciparum

• Published in: The Journal of infectious diseases 1984-12, Vol.150 (6), p.904-911
• Main Authors: Seaberg, Lavanya S., Parquette, Arlene R., Gluzman, I1ya Y., Phillips, Grady W., Brodasky, Thomas F., Krogstad, Donald J.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials; Antiparasitic agents; Biological and medical sciences; Chloroquine - pharmacology; Clindamycin - pharmacology; Dose response relationship; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Synergism; Erythrocytes; Falciparum malaria; Hypoxanthine; Hypoxanthines - metabolism; Infections; Malaria; Medical sciences; Nucleic acids; Original Articles; Parasites; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Plasmodium falciparum - metabolism; Protein synthesis; Trophozoites
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/150.6.904

The clindamycin dose-response curves observed with both chloroquine-resistant and chloroquine-susceptible strains of Plasmodium falciparum in vitro demonstrated a plateau region that extended from 10−2 to 101 µg/ml of drug (22 nM to 22 µM. Similar dose-response curves were also observed with the three major metabolites of clindamycin (clindamycin sulfoxide, de-N-methyl clindarnycin, and de-N-methyl clindamycin sulfoxide). The position of this plateau was time dependent and rose from 20%–25% to 90%–95% inhibition of parasite growth between 24 and 72 hr of exposure to the drug. Clindamycin treatment reduced plasmodial protein and nucleic acid synthesis (as measured by the incorporation of [3H]isoleucine and [3H]hypoxanthine, respectively) but 'did not interfere with knob formation. The combination of quinine plus a fixed concentration of clindamycin (0.1 µg/ml) inhibited growth of the quinine-resistant Indochina I strain, although most of the antiplasmodial activity observed at quinine concentrations