Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis.
Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX],...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797060802568519680 |
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| author | Chaowagul, W Chierakul, W Simpson, A Short, J Stepniewska, K Maharjan, B Rajchanuvong, A Busarawong, D Limmathurotsakul, D Cheng, A Wuthiekanun, V Newton, P White, N Day, N Peacock, S |
| author_facet | Chaowagul, W Chierakul, W Simpson, A Short, J Stepniewska, K Maharjan, B Rajchanuvong, A Busarawong, D Limmathurotsakul, D Cheng, A Wuthiekanun, V Newton, P White, N Day, N Peacock, S |
| author_sort | Chaowagul, W |
| collection | OXFORD |
| description | Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis. |
| first_indexed | 2024-03-06T20:22:03Z |
| format | Journal article |
| id | oxford-uuid:2e25222a-c2fb-4e8e-9df4-aa211324b149 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:22:03Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:2e25222a-c2fb-4e8e-9df4-aa211324b1492022-03-26T12:47:13ZOpen-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2e25222a-c2fb-4e8e-9df4-aa211324b149EnglishSymplectic Elements at Oxford2005Chaowagul, WChierakul, WSimpson, AShort, JStepniewska, KMaharjan, BRajchanuvong, ABusarawong, DLimmathurotsakul, DCheng, AWuthiekanun, VNewton, PWhite, NDay, NPeacock, SMelioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis. |
| spellingShingle | Chaowagul, W Chierakul, W Simpson, A Short, J Stepniewska, K Maharjan, B Rajchanuvong, A Busarawong, D Limmathurotsakul, D Cheng, A Wuthiekanun, V Newton, P White, N Day, N Peacock, S Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title | Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title_full | Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title_fullStr | Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title_full_unstemmed | Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title_short | Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. |
| title_sort | open label randomized trial of oral trimethoprim sulfamethoxazole doxycycline and chloramphenicol compared with trimethoprim sulfamethoxazole and doxycycline for maintenance therapy of melioidosis |
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