Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria

被引:116
作者
Borrmann, S
Issifou, S
Esser, G
Adegnika, AA
Ramharter, M
Matsiegui, PB
Oyakhirome, S
Mawili-Mboumba, DP
Missinou, MA
Kun, JFJ
Jomaa, H
Kremsner, PG
机构
[1] Univ Tubingen, Inst Trop Med, Dept Parasitol, D-72074 Tubingen, Germany
[2] Alberth Schweitzer Hosp, Med Res Unit, Lambarene, Gabon
[3] Univ Giessen, Inst Biochem, Giessen, Germany
[4] Univ Vienna, Dept Internal Med 1, Div Infect Dis, A-1010 Vienna, Austria
关键词
D O I
10.1086/424603
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1534 / 1540
页数:7
相关论文
共 25 条
[1]   Fosmidomycin-clindamycin for plasmodium falciparum infections in African children [J].
Borrmann, S ;
Adegnika, AA ;
Matsiegui, PB ;
Issifou, S ;
Schindler, A ;
Mawili-Mboumba, DP ;
Baranek, T ;
Wiesner, J ;
Jomaa, H ;
Kremsner, PG .
JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (05) :901-908
[2]   Evidence for the efficacy of artesunate in asymptomatic Plasmodium malariae infections [J].
Borrmann, S ;
Szlezák, N ;
Binder, RK ;
Missinou, MA ;
Lell, B ;
Kremsner, PG .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2002, 50 (05) :751-754
[3]  
DEHAAN RM, 1972, INT J CLIN PHARM TH, V6, P105
[4]   A plastid organelle as a drug target in apicomplexan parasites [J].
Fichera, ME ;
Roos, DS .
NATURE, 1997, 390 (6658) :407-409
[5]   The evolution of drug-resistant malaria: the role of drug elimination half-life [J].
Hastings, IM ;
Watkins, WM ;
White, NJ .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 2002, 357 (1420) :505-519
[6]   Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].
Jomaa, H ;
Wiesner, J ;
Sanderbrand, S ;
Altincicek, B ;
Weidemeyer, C ;
Hintz, M ;
Türbachova, I ;
Eberl, M ;
Zeidler, J ;
Lichtenthaler, HK ;
Soldati, D ;
Beck, E .
SCIENCE, 1999, 285 (5433) :1573-1576
[7]   CURING OF CHLOROQUINE-RESISTANT MALARIA WITH CLINDAMYCIN [J].
KREMSNER, PG ;
WINKLER, S ;
BRANDTS, C ;
GRANINGER, W ;
BIENZLE, U .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1993, 49 (05) :650-654
[8]  
KUEMMERLE HP, 1987, CHEMIOTERAPIA, V6, P113
[9]   Merozoite surface antigen 1 and 2 genotypes and resetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon [J].
Kun, JFJ ;
Schmidt-Ott, RJ ;
Lehman, LG ;
Lell, B ;
Luckner, D ;
Greve, B ;
Matousek, P ;
Kremsner, PG .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1998, 92 (01) :110-114
[10]   Malaria chemoprophylaxis with tafenoquine: a randomised study [J].
Lell, B ;
Faucher, JF ;
Missinou, MA ;
Borrmann, S ;
Dangelmaier, O ;
Horton, J ;
Kremsner, PG .
LANCET, 2000, 355 (9220) :2041-2045