Outcomes of Patients with Melioidosis Treated with Cotrimoxazole Alone for Eradication Therapy

Chusri, Sarunyou; Hortiwakul, Thanaporn; Charoenmak, Boonsri; Silpapojakul, Khachornsakdi

doi:10.4269/ajtmh.2012.12-0136

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…Co-trimoxazole alone has been used for several years for the eradication phase of treatment in northern Australia with apparently excellent results [45] . In 2013, a group from southern Thailand published their experience of using co-trimoxazole alone, with similarly good results [46] . In a retrospective review over a 10-year period, only 1 (3.2%) of 31 patients who received co-trimoxazole alone relapsed compared with 5 (4.6%) of 109 treated with co-trimoxazole plus doxycycline.…”

Section: Treatmentmentioning

confidence: 99%

Treatment and prophylaxis of melioidosis

Dance

2014

International Journal of Antimicrobial Agents

244

257

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Melioidosis, infection with Burkholderia pseudomallei, is being recognised with increasing frequency and is probably more common than currently appreciated. Treatment recommendations are based on a series of clinical trials conducted in Thailand over the past 25 years. Treatment is usually divided into two phases: in the first, or acute phase, parenteral drugs are given for ≥10 days with the aim of preventing death from overwhelming sepsis; in the second, or eradication phase, oral drugs are given, usually to complete a total of 20 weeks, with the aim of preventing relapse. Specific treatment for individual patients needs to be tailored according to clinical manifestations and response, and there remain many unanswered questions. Some patients with very mild infections can probably be cured by oral agents alone. Ceftazidime is the mainstay of acute-phase treatment, with carbapenems reserved for severe infections or treatment failures and amoxicillin/clavulanic acid (co-amoxiclav) as second-line therapy. Trimethoprim/sulfamethoxazole (co-trimoxazole) is preferred for the eradication phase, with the alternative of co-amoxiclav. In addition, the best available supportive care is needed, along with drainage of abscesses whenever possible. Treatment for melioidosis is unaffordable for many in endemic areas of the developing world, but the relative costs have reduced over the past decade. Unfortunately there is no likelihood of any new or cheaper options becoming available in the immediate future. Recommendations for prophylaxis following exposure to B. pseudomallei have been made, but the evidence suggests that they would probably only delay rather than prevent the development of infection.

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Section: Treatmentmentioning

confidence: 99%

Treatment and prophylaxis of melioidosis

Dance

2014

International Journal of Antimicrobial Agents

244

257

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“…This recommendation has not been tested in a clinical trial evaluating patient outcome. Alternatively, using the dosage of 160/800 mg twice daily for three months has been shown to be effective in eradication of the infection [ 70 ].…”

Section: Reviewmentioning

confidence: 99%

Cotrimoxazole - optimal dosing in the critically ill

Brown

2014

Ann Intensive Care

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The optimum dosage regimen for cotrimoxazole in the treatment of life threatening infections due to susceptible organisms encountered in critically ill patients is unclear despite decades of the drug’s use. Therapeutic drug monitoring to determine the appropriate dosing for successful infection eradication is not widely available. The clinician must utilize published pharmacokinetic, pharmacodynamic, and effective inhibitory concentration information to determine potential dosing regimens for individual patients when treating specific pathogens. Using minimum inhibitory concentrations known to successfully block growth for target pathogens, the pharmacokinetics of both trimethoprim and sulfamethoxazole can be utilized to establish empiric dosing regimens for critically ill patients while considering organ of clearance impairment. The author’s recommendations for appropriate dosing regimens are forwarded based on these parameters.

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“…Such adverse reactions often results in a switch to second-line treatment (usually amoxicillin-clavulanic acid), which is strongly associated with an increased risk of relapse 6 . Findings from a descriptive 10 year cohort study done in Australia reported recurrent infection in less than 2% of patients (one of 60 patients) who had oral treatment with TMP-SMX alone; 8 TMP-SMX has since become the standard regimen in Australia 3 and is occasionally used in Thailand 9 . We proposed that TMP-SMX alone was an adequate treatment for melioidosis, and did a clinical trial to compare the efficacy and safety of TMP-SMX versus TMP-SMX plus doxycycline for the oral treatment phase of melioidosis.…”

Section: Introductionmentioning

confidence: 99%

Trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (MERTH): a multicentre, double-blind, non-inferiority, randomised controlled trial

et al. 2014

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SummaryBackgroundMelioidosis, 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.MethodsFor 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.FindingsWe 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%]).InterpretationOur 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.FundingThailand Research Fund, the Melioidosis Research Center, the Center of Excellence in Specific Health Problems in Greater Mekong Sub-region cluster, and the Wellcome Trust.

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Outcomes of Patients with Melioidosis Treated with Cotrimoxazole Alone for Eradication Therapy

Cited by 12 publications

References 19 publications

Treatment and prophylaxis of melioidosis

Treatment and prophylaxis of melioidosis

Cotrimoxazole - optimal dosing in the critically ill

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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