Azithromycin Combination Therapy with Artesunate or Quinine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Adults: A Randomized, Phase 2 Clinical Trial in Thailand

Abstract

These data suggest that azithromycin-artesunate, even when given only once daily for 3 days, and azithromycin-quinine, given 3 times daily, are safe and efficacious combination treatments for uncomplicated falciparum malaria, and they deserve additional study in special patient populations.

In Vitro Antimalarial Activity of Azithromycin, Artesunate, and Quinine in Combination and Correlation with Clinical Outcome

“…Both drugs have in common that they are relatively fast acting and that they have short halflives. Despite the reduced in vitro drug sensitivity to quinine, the overall cure rates were similar in the artesunate and higherdose quinine arms (10).…”

“…Recently, azithromycin in combination with faster-acting antimalarials has demonstrated efficacy in phase 2 trials in treating P. falciparum malaria (3,8,10). As an antimalarial, azithromycin is relatively slow acting and therefore has to be combined with fast-acting compounds that will quickly reduce the initial parasite burden.…”

“…both in vitro (11,14) and in vivo for prophylaxis and treatment (1,3,4,6,8,10,15). Compared to other antibiotics used for malaria treatment (e.g., tetracyclines), azithromycin offers unique advantages due to its safety in children and experience with use in pregnant subjects (5), the populations most affected by malaria.…”

“…With an average terminal half-life of almost 3 days, azithromycin also has favorable pharmacokinetic properties, resulting in practical dosing regimens of as short as 3 days. Recent studies (8,10) indicate good efficacy in phase 2 trials for the treatment of uncomplicated falciparum malaria when used in combination with artesunate or quinine.…”

Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis

“…Like all macrolide antibiotics, it prevents bacteria from growing by interfering with their ability to make proteins. Its antiprotozoal activity has been shown both in vitro and in vivo as a mono or combination therapy against Toxoplasma gondii (Blais et al 1993), Cryptosporidium parvum (Hicks et al 1996), Acanthamoeba (Schuster and Visvesvara 1998), and Plasmodium (Noedl et al 2006). As it concentrates in tissues and especially in macrophages, and may reach levels 100 to 200 times higher than those in serum (Gladue et al 1989) therefore, its potential role as antileishmanial agent was evaluated.…”