title: Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria.
abstract: Fosmidomycin plus clindamycin was shown to be efficacious in the treatment of uncomplicated Plasmodium falciparum malaria in a small cohort of pediatric patients aged 7 to 14 years, but more data, including data on younger children with less antiparasitic immunity, are needed to determine the potential value of this new antimalarial combination. We conducted a single-arm study to improve the precision of efficacy estimates for an oral 3-day fixed-ratio combination of fosmidomycin and clindamycin at 30 and 10 mg/kg of body weight, respectively, every 12 hours for the treatment of uncomplicated P. falciparum malaria in 51 pediatric outpatients aged 1 to 14 years. Fosmidomycin plus clindamycin was generally well tolerated, but relatively high rates of treatment-associated neutropenia (8/51 [16%]) and falls of hemoglobin concentrations of > or =2 g/dl (7/51 [14%]) are of concern. Asexual parasites and fever were cleared within median periods of 42 h and 38 h, respectively. All patients who could be evaluated were parasitologically and clinically cured by day 14 (49/49; 95% confidence interval [CI], 93 to 100%). The per-protocol, PCR-adjusted day 28 cure rate was 89% (42/47; 95% CI, 77 to 96%). Efficacy appeared to be significantly reduced in children aged 1 to 2 years, with a day 28 cure rate of only 62% for this small subgroup (5/8). The inadequate efficacy in children of <3 years highlights the need for continued systematic studies of the current dosing regimen, which should include randomized trial designs.
authors.affiliation: Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lundgren
authors.forename: Sunny
authors.initials: S
authors.lastname: Oyakhirome
authors.forename: Bénido
authors.initials: B
authors.lastname: Impouma
authors.forename: Pierre-Blaise
authors.initials: PB
authors.lastname: Matsiegui
authors.forename: Ayola A
authors.initials: AA
authors.lastname: Adegnika
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: David
authors.initials: D
authors.lastname: Hutchinson
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
mesh_terms: 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; D005500:Follow-Up Studies; D005578:Fosfomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification
chemical_list: D000962:Antimalarials; D006454:Hemoglobins; D005578:Fosfomycin; D002981:Clindamycin; C024640:fosmidomycin