Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand

Antibiotics with antimalarial activity may offer an interesting alternative for the treatment of multidrug-resistant falciparum malaria. Azithromycin, a relatively recent semisynthetic derivative of erythromycin, was tested f or its in vitro activity against fresh isolates of Plasmodium falciparum. A s the reportedly slow onset of action of azithromycin suggests its combinat ion with fast-acting substances., such as artemisinin-derivatives, dihydroa rtemisinin (DHA) was tested parallel as a possible combination partner. The effective concentrations found for azithromycin in this study (EC50 = 29.3 mu mol/l, EC90 = 77.1 mu mol/l blood medium mixture (BMM)) are comparable to those of other antimalarials in the antibiotics class and are considerab ly higher than those found for mefloquine or quinine. The absence of an act ivity correlation between azithromycin and chloroquine, quinine and artemis inin emphasises the independence of azithromycin drug response from the sen sitivity to these drugs. A weak activity correlation (rho (EC90) = 0.352 p = 0.028), which could point to a potential cross-sensitivity but is probabl y of little clinical importance, was found with mefloquine above the EC50 l evel. Provided that further clinical trials support the combination of thes e drugs, DHA may offer an interesting combination partner for azithromycin owing to its rapid onset of action and the comparatively low effective conc entrations (EC50 = 1.65 nmol/l, EC90 = 7.10 nmol/l BMM). This combination m ay serve as an interesting alternative for tetracycline and doxycycline, wh ich cannot be used in pregnant women and children, and exhibit phototoxicit y. Nevertheless, the relatively high cost of this combination, as well as t he controversial reports of the clinical efficacy, may limit the usefulness of azithromycin in malaria therapy and require an adjustment of previously used treatment regimens. (C) 2001 Elsevier Science B.V. All rights reserve d.