Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria.
It has been demonstrated that fosmidomycin has good tolerability and rapid onset of action, but late recrudescences preclude its use alone; in vitro, clindamycin has been shown to act synergistically with fosmidomycin against Plasmodium falciparum. We conducted a study in pediatric outpatients with P. falciparum malaria in Gabon to evaluate the efficacy and safety of an oral combination of fosmidomycin-clindamycin of 30 mg/kg and 10 mg/kg of body weight, respectively, every 12 h. Patients 7-14 years old were recruited in cohorts of 10. The first 10 patients were treated for 5 days. The duration of treatment was then incrementally shortened in intervals of 1 day if >85% of the patients in a cohort were cured by day 14. All dosing regimens were well tolerated, and no serious adverse events occurred. Asexual parasites and fever rapidly cleared in all patients. Cure ratios of 100% on day 14 were achieved with treatment durations of 5 (10/10 patients), 4 (10/10 patients), 3 (10/10 patients), and 2 days (10/10 patients); 1 day of treatment led to a cure ratio of 50% (5/10 patients). Fosmidomycin-clindamycin is safe and well tolerated, and short-course regimens achieved high efficacy in children with P. falciparum malaria. Fosmidomycin-clindamycin is a promising novel treatment option for malaria.
Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon, Germany.
Steffen
S
Borrmann
Saadou
S
Issifou
Gilbert
G
Esser
Ayola A
AA
Adegnika
Michael
M
Ramharter
Pierre-Blaise
PB
Matsiegui
Sunny
S
Oyakhirome
Dénise P
DP
Mawili-Mboumba
Michel A
MA
Missinou
Jürgen F J
JF
Kun
Hassan
H
Jomaa
Peter G
PG
Kremsner
D000284:Administration, Oral; D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001769:Blood / Q000469:parasitology; D002648:Child; D002981:Clindamycin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D005334:Fever; D005578:Fosfomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D005681:Gabon; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification
D000962:Antimalarials; D005578:Fosfomycin; D002981:Clindamycin; C024640:fosmidomycin