Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial
Summary Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei , is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on tria...
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| Veröffentlicht in: | The Lancet (British edition) 2014-03, Vol.383 (9919), p.807-814 |
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| creator | Chetchotisakd, Ploenchan, Prof Chierakul, Wirongrong, MD Chaowagul, Wipada, Prof Anunnatsiri, Siriluck, MD Phimda, Kriangsak, MD Mootsikapun, Piroon, MD Chaisuksant, Seksan, MD Pilaikul, Jiraporn, MD Thinkhamrop, Bandit, PhD Phiphitaporn, Sunchai, MD Susaengrat, Wattanachai, MD Toondee, Chalongchai, MD Wongrattanacheewin, Surasakdi, PhD Wuthiekanun, Vanaporn, BSc Chantratita, Narisara, PhD Thaipadungpanit, Janjira, PhD Day, Nicholas P, Prof Limmathurotsakul, Direk, Dr Peacock, Sharon J, Prof |
| description | Summary Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei , is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1·7. This study is registered with www.controlled-trials.com , number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0·81; 95% CI 0·42–1·55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. Funding Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust. |
| doi_str_mv | 10.1016/S0140-6736(13)61951-0 |
| format | Article |
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Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1·7. This study is registered with www.controlled-trials.com , number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0·81; 95% CI 0·42–1·55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. Funding Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(13)61951-0</identifier><identifier>PMID: 24284287</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Administration, Oral ; Adult ; Anti-Bacterial Agents - administration & dosage ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimicrobial agents ; Bacillus ; Bacterial diseases ; Biological and medical sciences ; Double-Blind Method ; Doxycycline - administration & dosage ; Drug therapy ; Fatalities ; Female ; General aspects ; Health problems ; Human bacterial diseases ; Humans ; Infectious diseases ; Internal Medicine ; Kaplan-Meier Estimate ; Male ; Medical sciences ; Melioidosis ; Melioidosis - drug therapy ; Melioidosis - mortality ; Middle Aged ; Mortality ; Pharmacology. Drug treatments ; Recurrence ; Side effects ; Thailand - epidemiology ; Treatment Outcome ; Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage ; Tropical bacterial diseases</subject><ispartof>The Lancet (British edition), 2014-03, Vol.383 (9919), p.807-814</ispartof><rights>Chetchotisakd et al. Open Access article distributed under the terms of CC BY</rights><rights>2014 Chetchotisakd et al. Open Access article distributed under the terms of CC BY</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2014 Chetchotisakd et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Mar 1, 2014</rights><rights>2014 Chetchotisakd et al. Open Access article distributed under the terms of CC BY 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-2ff919271403d13ddbaeeecf369c4dd1c0e681b46baaa8648912427014966a683</citedby><cites>FETCH-LOGICAL-c543t-2ff919271403d13ddbaeeecf369c4dd1c0e681b46baaa8648912427014966a683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673613619510$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28212818$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24284287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chetchotisakd, Ploenchan, Prof</creatorcontrib><creatorcontrib>Chierakul, Wirongrong, MD</creatorcontrib><creatorcontrib>Chaowagul, Wipada, Prof</creatorcontrib><creatorcontrib>Anunnatsiri, Siriluck, MD</creatorcontrib><creatorcontrib>Phimda, Kriangsak, MD</creatorcontrib><creatorcontrib>Mootsikapun, Piroon, MD</creatorcontrib><creatorcontrib>Chaisuksant, Seksan, MD</creatorcontrib><creatorcontrib>Pilaikul, Jiraporn, MD</creatorcontrib><creatorcontrib>Thinkhamrop, Bandit, PhD</creatorcontrib><creatorcontrib>Phiphitaporn, Sunchai, MD</creatorcontrib><creatorcontrib>Susaengrat, Wattanachai, MD</creatorcontrib><creatorcontrib>Toondee, Chalongchai, MD</creatorcontrib><creatorcontrib>Wongrattanacheewin, Surasakdi, PhD</creatorcontrib><creatorcontrib>Wuthiekanun, Vanaporn, BSc</creatorcontrib><creatorcontrib>Chantratita, Narisara, PhD</creatorcontrib><creatorcontrib>Thaipadungpanit, Janjira, PhD</creatorcontrib><creatorcontrib>Day, Nicholas P, Prof</creatorcontrib><creatorcontrib>Limmathurotsakul, Direk, Dr</creatorcontrib><creatorcontrib>Peacock, Sharon J, Prof</creatorcontrib><title>Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Summary Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei , is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1·7. This study is registered with www.controlled-trials.com , number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0·81; 95% CI 0·42–1·55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. Funding Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimicrobial agents</subject><subject>Bacillus</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Double-Blind Method</subject><subject>Doxycycline - administration & dosage</subject><subject>Drug therapy</subject><subject>Fatalities</subject><subject>Female</subject><subject>General aspects</subject><subject>Health problems</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Internal Medicine</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melioidosis</subject><subject>Melioidosis - drug therapy</subject><subject>Melioidosis - mortality</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Pharmacology. Drug treatments</subject><subject>Recurrence</subject><subject>Side effects</subject><subject>Thailand - epidemiology</subject><subject>Treatment Outcome</subject><subject>Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage</subject><subject>Tropical bacterial diseases</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNktGK1DAUhoso7rj6CEpAhFmYatKkmXYvVmRZXWFF0BG8C5nk1M2aacakHXZ8Th_I05lxVvdChUJa-p2Pc07-LHvM6HNGmXzxkTJBcznlcsz4kWR1yXJ6JxsxMRV5Kaaf72ajPXKQPUjpilIqJC3vZweFKCp8pqPsxyy6BXSXYYlnnnrf6M3ntf4ePJAVxNQn0v0VWnpEbLhem7XxrgWiEwlRewJRW2d051aACtDdAtqONCGSBXgXnA3JJTJ-d_Zhdn50TDRZ9L5zBqEIEzT2cw_5HJV2QtrQ5q5tILoQXbeekKhbGxYugSUmYEXwHl-xU-0fZvca7RM82p2H2afXZ7PT8_zi_Zu3p68uclMK3uVF09SsLqa4JW4Zt3auAcA0XNZGWMsMBVmxuZBzrXUlRVUzXNwUt1pLqWXFD7OTrXfZzxdgN41rr4Yt6bhWQTv155_WXaovYaV4zeuaMxSMd4IYvvWQOoUDGfBetxD6pFhZUF4JUdL_QKlAvJAFok9voVehjy1uAimGvrKsBmG5pUwMKUVo9n0zqoaIqU3E1JAfxbjaREwNdU9-H3pf9StTCDzbAToZ7Ru8KOPSDVcVrKjYsL2XWw7wilYOokrGQWvAugimUza4f7Zycssw5A8T57_CGtLN1CoVim4lg4PxjYHynzX-CW8</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>Chetchotisakd, Ploenchan, Prof</creator><creator>Chierakul, Wirongrong, MD</creator><creator>Chaowagul, Wipada, Prof</creator><creator>Anunnatsiri, Siriluck, MD</creator><creator>Phimda, Kriangsak, MD</creator><creator>Mootsikapun, Piroon, MD</creator><creator>Chaisuksant, Seksan, MD</creator><creator>Pilaikul, Jiraporn, MD</creator><creator>Thinkhamrop, Bandit, PhD</creator><creator>Phiphitaporn, Sunchai, MD</creator><creator>Susaengrat, Wattanachai, MD</creator><creator>Toondee, Chalongchai, MD</creator><creator>Wongrattanacheewin, Surasakdi, PhD</creator><creator>Wuthiekanun, Vanaporn, BSc</creator><creator>Chantratita, Narisara, PhD</creator><creator>Thaipadungpanit, Janjira, PhD</creator><creator>Day, Nicholas P, Prof</creator><creator>Limmathurotsakul, Direk, Dr</creator><creator>Peacock, Sharon J, Prof</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140301</creationdate><title>Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial</title><author>Chetchotisakd, Ploenchan, Prof ; 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Drug treatments</topic><topic>Recurrence</topic><topic>Side effects</topic><topic>Thailand - epidemiology</topic><topic>Treatment Outcome</topic><topic>Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage</topic><topic>Tropical bacterial diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chetchotisakd, Ploenchan, Prof</creatorcontrib><creatorcontrib>Chierakul, Wirongrong, MD</creatorcontrib><creatorcontrib>Chaowagul, Wipada, Prof</creatorcontrib><creatorcontrib>Anunnatsiri, Siriluck, MD</creatorcontrib><creatorcontrib>Phimda, Kriangsak, MD</creatorcontrib><creatorcontrib>Mootsikapun, Piroon, MD</creatorcontrib><creatorcontrib>Chaisuksant, Seksan, MD</creatorcontrib><creatorcontrib>Pilaikul, Jiraporn, MD</creatorcontrib><creatorcontrib>Thinkhamrop, Bandit, PhD</creatorcontrib><creatorcontrib>Phiphitaporn, Sunchai, MD</creatorcontrib><creatorcontrib>Susaengrat, Wattanachai, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chetchotisakd, Ploenchan, Prof</au><au>Chierakul, Wirongrong, MD</au><au>Chaowagul, Wipada, Prof</au><au>Anunnatsiri, Siriluck, MD</au><au>Phimda, Kriangsak, MD</au><au>Mootsikapun, Piroon, MD</au><au>Chaisuksant, Seksan, MD</au><au>Pilaikul, Jiraporn, MD</au><au>Thinkhamrop, Bandit, PhD</au><au>Phiphitaporn, Sunchai, MD</au><au>Susaengrat, Wattanachai, MD</au><au>Toondee, Chalongchai, MD</au><au>Wongrattanacheewin, Surasakdi, PhD</au><au>Wuthiekanun, Vanaporn, BSc</au><au>Chantratita, Narisara, PhD</au><au>Thaipadungpanit, Janjira, PhD</au><au>Day, Nicholas P, Prof</au><au>Limmathurotsakul, Direk, Dr</au><au>Peacock, Sharon J, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>383</volume><issue>9919</issue><spage>807</spage><epage>814</epage><pages>807-814</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Summary Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei , is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1·7. This study is registered with www.controlled-trials.com , number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0·81; 95% CI 0·42–1·55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients. Funding Thailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>24284287</pmid><doi>10.1016/S0140-6736(13)61951-0</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2014-03, Vol.383 (9919), p.807-814 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3939931 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Administration, Oral Adult Anti-Bacterial Agents - administration & dosage Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Antimicrobial agents Bacillus Bacterial diseases Biological and medical sciences Double-Blind Method Doxycycline - administration & dosage Drug therapy Fatalities Female General aspects Health problems Human bacterial diseases Humans Infectious diseases Internal Medicine Kaplan-Meier Estimate Male Medical sciences Melioidosis Melioidosis - drug therapy Melioidosis - mortality Middle Aged Mortality Pharmacology. Drug treatments Recurrence Side effects Thailand - epidemiology Treatment Outcome Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage Tropical bacterial diseases |
| title | Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial |
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