Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis

Allen Cheng, Emma S. McBryde, Vanaporn Wuthiekanun, W Chierakul, P Amornchai, Nicholas Day, Sharon J Peacock

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (?1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of ?1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of ?1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis. � 2009, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)4193-4199
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number10
Publication statusPublished - 2009

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Melioidosis
Sulfamethoxazole Drug Combination Trimethoprim
Pharmacokinetics
Thailand
Thymidine Monophosphate
Microbiology
Protein Binding
Population
Biological Availability
Communicable Diseases
Body Weight
Anti-Bacterial Agents
Weights and Measures
Recurrence

Cite this

Cheng, A., McBryde, E. S., Wuthiekanun, V., Chierakul, W., Amornchai, P., Day, N., & Peacock, S. J. (2009). Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. Antimicrobial Agents and Chemotherapy, 53(10), 4193-4199.
Cheng, Allen ; McBryde, Emma S. ; Wuthiekanun, Vanaporn ; Chierakul, W ; Amornchai, P ; Day, Nicholas ; Peacock, Sharon J. / Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 10. pp. 4193-4199.
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abstract = "Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (?1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of ?1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of ?1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis. � 2009, American Society for Microbiology. All Rights Reserved.",
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Cheng, A, McBryde, ES, Wuthiekanun, V, Chierakul, W, Amornchai, P, Day, N & Peacock, SJ 2009, 'Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis', Antimicrobial Agents and Chemotherapy, vol. 53, no. 10, pp. 4193-4199.

Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. / Cheng, Allen; McBryde, Emma S.; Wuthiekanun, Vanaporn; Chierakul, W; Amornchai, P; Day, Nicholas; Peacock, Sharon J.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 10, 2009, p. 4193-4199.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis

AU - Cheng, Allen

AU - McBryde, Emma S.

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AU - Day, Nicholas

AU - Peacock, Sharon J

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N2 - Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (?1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of ?1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of ?1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis. � 2009, American Society for Microbiology. All Rights Reserved.

AB - Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (?1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of ?1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of ?1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis. � 2009, American Society for Microbiology. All Rights Reserved.

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Cheng A, McBryde ES, Wuthiekanun V, Chierakul W, Amornchai P, Day N et al. Dosing regimens of cotrimoxazole (trimethoprim-sulfamethoxazole) for melioidosis. Antimicrobial Agents and Chemotherapy. 2009;53(10):4193-4199.