In vitro activity of tigecycline in Plasmodium falciparum culture-adapted strains and clinical isolates from Gabon

Abstract

Emerging drug resistance in Plasmodium falciparum and its rapid spread in endemic countries have made the quest for new antimalarials a research priority. Tetracycline and its derivatives are well-established compounds for combination with faster-acting drugs in the current practice of malaria treatment. Tigecycline is the first marketed derivative of a new class of tetracycline antibiotics. Its altered structure leads to enhanced activity against bacteria and may also be associated with improved antimalarial activity. Using the histidine-rich protein 2 (HRP2) drug sensitivity assay, we determined the geometric mean 50% inhibitory concentrations (IC(50)) of tigecycline in culture-adapted strains as well as in 23 clinical P. falciparum isolates from Lambaréné, Gabon. These values were compared with other tetracyclines as well as with clindamycin. Assays with 3 days and 6 days of incubation were evaluated to explore the impact of delayed parasite death on drug activity. IC(50) values in clinical isolates after 6 days of incubation were 160.0 nM [95% confidence interval (CI) 114.6-223.4 nM] for tigecycline, 739.4 nM (445.9-1226.1 nM) for doxycycline and 9.2 nM (95% CI 6.6-12.9 nM) for clindamycin. Tigecycline was found to act faster against plasmodia than any of the other antibiotics tested. This study demonstrates the potential of tetracycline derivatives in the development of improved antimalarials.