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...
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| Veröffentlicht in: | The Journal of infectious diseases 2004-11, Vol.190 (9), p.1534-1540 |
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| creator | Borrmann, Steffen Issifou, Saadou Esser, Gilbert Adegnika, Ayola A. Ramharter, Michael Matsiegui, Pierre-Blaise Oyakhirome, Sunny Mboumba, Dénise P. Mawili Missinou, Michel A. Kun, Jürgen F. J. Jomaa, Hassan Kremsner, Peter G. |
| description | 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). Fosmidomycinclindamycin 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. |
| doi_str_mv | 10.1086/424603 |
| format | Article |
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Mawili ; Missinou, Michel A. ; Kun, Jürgen F. J. ; Jomaa, Hassan ; Kremsner, Peter G.</creator><creatorcontrib>Borrmann, Steffen ; Issifou, Saadou ; Esser, Gilbert ; Adegnika, Ayola A. ; Ramharter, Michael ; Matsiegui, Pierre-Blaise ; Oyakhirome, Sunny ; Mboumba, Dénise P. Mawili ; Missinou, Michel A. ; Kun, Jürgen F. J. ; Jomaa, Hassan ; Kremsner, Peter G.</creatorcontrib><description>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). Fosmidomycinclindamycin 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.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/424603</identifier><identifier>PMID: 15478056</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Administration, Oral ; Adolescent ; Animals ; Antimalarials ; Antimalarials - administration & dosage ; Antimalarials - adverse effects ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Biological and medical sciences ; Blood - parasitology ; Blood plasma ; Child ; Clindamycin - administration & dosage ; Clindamycin - adverse effects ; Clindamycin - pharmacology ; Clindamycin - therapeutic use ; Dosage ; Drug Therapy, Combination - therapeutic use ; Falciparum malaria ; Female ; Fever ; Fosfomycin - administration & dosage ; Fosfomycin - adverse effects ; Fosfomycin - analogs & derivatives ; Fosfomycin - pharmacology ; Fosfomycin - therapeutic use ; Fundamental and applied biological sciences. Psychology ; Gabon ; Human protozoal diseases ; Humans ; Infections ; Infectious diseases ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - parasitology ; Male ; Medical cures ; Medical sciences ; Microbiology ; Parasitemia ; Parasites ; Parasitic diseases ; Parasitology ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - isolation & purification ; Protozoal diseases</subject><ispartof>The Journal of infectious diseases, 2004-11, Vol.190 (9), p.1534-1540</ispartof><rights>Copyright 2004 Infectious Diseases Society of America</rights><rights>2004 by the Infectious Diseases Society of America 2004</rights><rights>2005 INIST-CNRS</rights><rights>Copyright University of Chicago Press Nov 1, 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-7dcfe16da8428d088a24b3a137dfbde8224f6d0e13bf17cb7206f9c1879187a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30077889$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30077889$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16311815$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15478056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Borrmann, Steffen</creatorcontrib><creatorcontrib>Issifou, Saadou</creatorcontrib><creatorcontrib>Esser, Gilbert</creatorcontrib><creatorcontrib>Adegnika, Ayola A.</creatorcontrib><creatorcontrib>Ramharter, Michael</creatorcontrib><creatorcontrib>Matsiegui, Pierre-Blaise</creatorcontrib><creatorcontrib>Oyakhirome, Sunny</creatorcontrib><creatorcontrib>Mboumba, Dénise P. Mawili</creatorcontrib><creatorcontrib>Missinou, Michel A.</creatorcontrib><creatorcontrib>Kun, Jürgen F. J.</creatorcontrib><creatorcontrib>Jomaa, Hassan</creatorcontrib><creatorcontrib>Kremsner, Peter G.</creatorcontrib><title>Fosmidomycin-Clindamycin for the Treatment of Plasmodium falciparum Malaria</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><addtitle>J Infect Dis</addtitle><description>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). Fosmidomycinclindamycin 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.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Animals</subject><subject>Antimalarials</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - adverse effects</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood - parasitology</subject><subject>Blood plasma</subject><subject>Child</subject><subject>Clindamycin - administration & dosage</subject><subject>Clindamycin - adverse effects</subject><subject>Clindamycin - pharmacology</subject><subject>Clindamycin - therapeutic use</subject><subject>Dosage</subject><subject>Drug Therapy, Combination - therapeutic use</subject><subject>Falciparum malaria</subject><subject>Female</subject><subject>Fever</subject><subject>Fosfomycin - administration & dosage</subject><subject>Fosfomycin - adverse effects</subject><subject>Fosfomycin - analogs & derivatives</subject><subject>Fosfomycin - pharmacology</subject><subject>Fosfomycin - therapeutic use</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gabon</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Male</subject><subject>Medical cures</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Parasitemia</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Parasitology</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - isolation & purification</subject><subject>Protozoal diseases</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kV1rFDEUhoModl31HyijoHej-ZokcymLbaVVC92L4k04kw_MOjNZkxmw_76ps2xB8CKcQ96H9-S8QeglwR8IVuIjp1xg9gitSMNkLQRhj9EKY0protr2BD3LeYcx5kzIp-iENFwq3IgVujiNeQg2DrcmjPWmD6OFv33lY6qmn67aJgfT4Mapir666iEP0YZ5qDz0JuwhlfYr9JACPEdPymV2Lw51jbann7eb8_ry-9mXzafL2nDeTrW0xjsiLChOlcVKAeUdA8Kk9Z11ilLuhcWOsM4TaTpJsfCtIUq25QBbo_eL7T7F37PLkx5CNq7vYXRxzppIiVXTtAV8-w-4i3May9M0pawlRJY8jm4mxZyT83qfwgDpVhOs76PVS7QFfH1wm7vB2QfskGUB3h0AyAZ6n2A0IT9wghGiyves0ZuFi_P-_8NeLcwuTzEdKYaxlErdr1YvesiT-3PUIf3SQjLZ6PObH5qri2838upaX7M7JwyiAQ</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Borrmann, Steffen</creator><creator>Issifou, Saadou</creator><creator>Esser, Gilbert</creator><creator>Adegnika, Ayola A.</creator><creator>Ramharter, Michael</creator><creator>Matsiegui, Pierre-Blaise</creator><creator>Oyakhirome, Sunny</creator><creator>Mboumba, Dénise P. Mawili</creator><creator>Missinou, Michel A.</creator><creator>Kun, Jürgen F. J.</creator><creator>Jomaa, Hassan</creator><creator>Kremsner, Peter G.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>M7N</scope></search><sort><creationdate>20041101</creationdate><title>Fosmidomycin-Clindamycin for the Treatment of Plasmodium falciparum Malaria</title><author>Borrmann, Steffen ; Issifou, Saadou ; Esser, Gilbert ; Adegnika, Ayola A. ; Ramharter, Michael ; Matsiegui, Pierre-Blaise ; Oyakhirome, Sunny ; Mboumba, Dénise P. Mawili ; Missinou, Michel A. ; Kun, Jürgen F. 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Psychology</topic><topic>Gabon</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Male</topic><topic>Medical cures</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Parasitemia</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Parasitology</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - isolation & purification</topic><topic>Protozoal diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borrmann, Steffen</creatorcontrib><creatorcontrib>Issifou, Saadou</creatorcontrib><creatorcontrib>Esser, Gilbert</creatorcontrib><creatorcontrib>Adegnika, Ayola A.</creatorcontrib><creatorcontrib>Ramharter, Michael</creatorcontrib><creatorcontrib>Matsiegui, Pierre-Blaise</creatorcontrib><creatorcontrib>Oyakhirome, Sunny</creatorcontrib><creatorcontrib>Mboumba, Dénise P. 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Mawili</au><au>Missinou, Michel A.</au><au>Kun, Jürgen F. J.</au><au>Jomaa, Hassan</au><au>Kremsner, Peter G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fosmidomycin-Clindamycin for the Treatment of Plasmodium falciparum Malaria</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>J Infect Dis</stitle><addtitle>J Infect Dis</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>190</volume><issue>9</issue><spage>1534</spage><epage>1540</epage><pages>1534-1540</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>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). Fosmidomycinclindamycin 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.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>15478056</pmid><doi>10.1086/424603</doi><tpages>7</tpages></addata></record> |
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| ispartof | The Journal of infectious diseases, 2004-11, Vol.190 (9), p.1534-1540 |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Administration, Oral Adolescent Animals Antimalarials Antimalarials - administration & dosage Antimalarials - adverse effects Antimalarials - pharmacology Antimalarials - therapeutic use Biological and medical sciences Blood - parasitology Blood plasma Child Clindamycin - administration & dosage Clindamycin - adverse effects Clindamycin - pharmacology Clindamycin - therapeutic use Dosage Drug Therapy, Combination - therapeutic use Falciparum malaria Female Fever Fosfomycin - administration & dosage Fosfomycin - adverse effects Fosfomycin - analogs & derivatives Fosfomycin - pharmacology Fosfomycin - therapeutic use Fundamental and applied biological sciences. Psychology Gabon Human protozoal diseases Humans Infections Infectious diseases Malaria Malaria, Falciparum - drug therapy Malaria, Falciparum - parasitology Male Medical cures Medical sciences Microbiology Parasitemia Parasites Parasitic diseases Parasitology Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - isolation & purification Protozoal diseases |
| title | Fosmidomycin-Clindamycin for the Treatment of Plasmodium falciparum Malaria |
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