Evaluation of Fosmidomycin, in Combination with Clindamycin, in Adult Patients with Acute Uncomplicated Plasmodium falciparum Malaria

Abstract

Abstract

The treatment of malaria is becoming increasingly difficult due to the development of Plasmodium falciparum strains that are resistant to the commonly used antimalarials. It has been shown that fosmidomycin can be used alone to treat uncomplicated P. falciparum infection. However, a high rate of recrudescence has been noted. In Thailand, fosmidomycin alone gave a 100% cure rate at 7 days’ follow-up, but only 22% at 28 days. In Gabon, fosmidomycin yielded a 100% cure rate at 7 days’ follow-up and 78% at 28 days. Therefore, there is a need to find suitable combinations to treat P. falciparum and prevent recrudescence. Clindamycin has been shown to be synergistic in isobolograms. The potentiation of fosmidomycin by clindamycin has also been observed in vivo in a P. vinckei mouse model, in which co-administration resulted in a significantly higher cure rate than individual administration. Enhanced activity was also evident when the drugs were co-administered in the presence of high parasitemia. Combination therapy with fosmidomycin and clindamycin was highly effective with 100% cure rate 28 days’ follow-up. No serious adverse effect was found. Only some cases of diarrhea, vomiting and dizziness were reported.

Keywords: falciparum malaria; fosmidomycin; clindamycin