Maintenance therapy of melioidosis with ciprofloxacin plus azithromycin compared with cotrimoxazole plus doxycycline.

Abstract

Abstract. This is a report of a randomized, open, labeled study of the maintenance treatment of melioidosis using a combination of ciprofloxacin and azithromycin (Regimen A) for 12 weeks versus a combination of cotrimoxazole and doxycycline (Regimen B) for 20 weeks. The study was conducted at two tertiary-care hospitals in northeast Thailand. A total 65 patients were enrolled, 36 and 29, respectively, between August 1997 and July 1998. Subjects were randomly allocated to each arm of the trial, resulting in 32 treated under Regimen A and 33 in B. The main outcome was a culture-proven relapse in melioidosis. There were more relapses under Regimen A at 22% (7 of 32) than in Regimen B, 3% (1 of 33). The 19% difference in the rates was significant (95% confidence interval [CI]: 3% to 34%; exact P-value ϭ 0.027). Based on our data, a combination of cotrimoxazole and doxycycline treatment for 20 weeks should be given further consideration as the maintenance therapy of choice for melioidosis.

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

“…However, the objective endpoint of cultureconfirmed recurrences in our study is quite low compared with other studies. 4,8,10,12,14 In addition, compliance with follow-up was good. All of our patients had attended the follow-up clinics for at least 1 year and most of them received oral therapy for longer than 20 weeks.…”

“…4,5 However, the choice and duration of antibiotic treatment to prevent these recurrences remains unsettled, as evidenced by several different regimen reported in the literatures during the last two decades. 5,8,[10][11][12]14 The currently recommended eradication therapy with the combination of cotrimoxazole and doxycycline, given for 12-20 weeks, has decreased the 1-year recurrence rate of culture-proven melioidosis to~6%. 8 In our study, the 5% recurrence rates in patients who had received this combination regimen drugs is comparable to that of the original clinical trial and the 3.2% culture-proven recurrence rate in recipients of cotrimoxazole alone is quite low.…”

“…8 Because poor adherence to treatment are associated with recurrence of the disease, 5 other less toxic, alternative eradication regimens including amoxicillin-clavulanate with supplemental amoxicillin, quinolone monotherapy, and a combination of azithromycin and ciprofloxacin, have been tried. [10][11][12] However, all these regimens were associated with recurrence rates exceeding 15% and another simple but more effective regimen is needed. [10][11][12] Cotrimoxazole alone had been successfully used to treat an acute form of melioidosis in the Philippines and is used for eradication therapy in Australia.…”

“…[10][11][12] However, all these regimens were associated with recurrence rates exceeding 15% and another simple but more effective regimen is needed. [10][11][12] Cotrimoxazole alone had been successfully used to treat an acute form of melioidosis in the Philippines and is used for eradication therapy in Australia. 5,13 However, there are no published studies that have compared the effectiveness and side-effect profile of cotrimoxazole monotherapy with that of the co-trimoxazole plus doxycycline for the eradication treatment of this condition.…”

Evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis for experimental murine melioidosis

“…Interestingly, treatment failure and relapse were both significantly higher with this regimen than with a combination of co-trimoxazole and doxycycline [11].…”