The Journal of Infectious Diseases · 2004 · 134 citations · 20 references
PharmacyInfectious DiseasesPharmacologyChemotherapyClinical PharmacologyPediatric Infectious DiseasesAntimicrobial DosingAntiparasitic PharmacotherapyCombination Antimicrobial TherapyMalariaPediatric Antibiotic TherapyPediatric Antimicrobial TherapyAntimalarial ChemotherapyAntimalarial Drug CombinationsChemotherapy Of MalariaClindamycin TherapyOral Combination TherapyPlasmodium FalciparumTherapy TolerabilityTreatment Of 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.
20
Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs
Hassan Jomaa, Jochen Wiesner, Silke Sanderbrand et al. · Science · 1999 · 1.2K citations
A plastid organelle as a drug target in apicomplexan parasites
Maria E. Fichera, David S. Roos · Nature · 1997 · 587 citations
Life Sciences, Biology, Cell Biology +15
Michel A. Missinou, Steffen Borrmann, Andreas Schindler et al. · The Lancet · 2002 · 221 citations