Clinical Efficacy of Combination of Rifampin and Streptomycin for Treatment ofMycobacterium ulceransDisease

Abstract

We have evaluated the clinical efficacy of the combination of oral rifampin at 10 mg/kg of body weight and intramuscular streptomycin at 15 mg/kg for 8 weeks (RS8), as recommended by the WHO, in 160 PCRconfirmed cases of Mycobacterium ulcerans disease. In 152 patients (95%) with all forms of disease from early nodules to large ulcers, with or without edema, the lesions healed without recourse to surgery. Eight patients whose ulcers were healing poorly had skin grafting after completion of antibiotics. There were no recurrences among 158 patients reviewed at the 1-year follow-up. The times to complete healing ranged from 2 to 48 weeks, according to the type and size of the lesion, but the average rate of healing (rate of reduction in ulcer diameter) varied widely. Thirteen subjects had positive cultures for M. ulcerans during or after treatment, but all the lesions healed without further antibiotic treatment. Adverse events were rare. These results confirm the efficacy of RS8 delivered in a community setting.Mycobacterium ulcerans disease, known as Buruli ulcer, is a chronic subcutaneous infection which is common in humid rural tropical areas. The majority of patients are children aged less than 15 years living in rural areas remote from a hospital (29). Infection initially manifests as a painless nodule or plaque which breaks down centrally to form an ulcer with undermined edges (11). In a small proportion of lesions, there is edema around the ulcer which spreads rapidly, resulting in a very large ulcer. Significant morbidity results from Mycobacterium ulcerans disease when there is extensive scarring or functional limitation from contractures at joints, and there is occasionally a need for amputation of a limb. Ulcers or scars rarely undergo malignant transformation (12).Until recently, the mainstay of treatment for Buruli ulcer was excision of lesions with a wide margin to ensure complete removal of infected tissue. Recurrence rates after surgery varied between 6 and 17%, depending on the type and extent of the lesion and on the experience and skill of the surgeon (1,6,22). Recent evidence that antibiotics are effective has shifted the balance between surgery and antibiotics. In vitro, M. ulcerans has been shown to be susceptible to rifampin (13), aminoglycosides (7), macrolides (21), and quinolones (26). Infection of mouse footpads has been used as a model for susceptibility testing, and after treatment with the same antibiotics, the lesions became smaller and the total number of M. ulcerans organisms in tissue was reduced (2,8,25). The combination of rifampin with amikacin or streptomycin for 8 weeks has been the most effective in reducing the bacterial load in a number of studies, and the low relapse rate after treatment suggested that this combination was bactericidal (2, 15). An important reason for using more than one drug is that resistant mutants were found after rifampin monotherapy in mice (16).The bactericidal effect of rifampin at 10 mg/kg of body weight orally combined with streptomycin at 15 mg/k...

Challenges Associated with Management of Buruli Ulcer/Human Immunodeficiency Virus Coinfection in a Treatment Center in Ghana: A Case Series Study

“…1,5,6 The efficacy of this treatment regimen has been confirmed in several studies. [7][8][9] Active lesions present with large focal clusters of extracellular acid-fast bacilli (AFB) and only minor leukocyte infiltration. 10,11 Antimicrobial therapy leads to massive leukocyte infiltration, which culminates in the development of ectopic lymphoid structures in the lesions.…”

Buruli ulcer: wound care and rehabilitation

“…8,11,59,[61][62][63] This is important because it can be confused with recurrence. Paradoxical reaction is defined as an episode of new inflammation, with or without pus formation, with significant enlargement of a healing lesion during or after antibiotic treatment.…”

“…This has been shown to result in healing of all forms of M. ulcerans disease with few exceptions. 8 expert advisors after a study showed that M. ulcerans organisms were still viable in early lesions excised after treatment for 2 weeks, whereas cultures were sterile when treatment was extended to 4 weeks, 8 weeks, or 12 weeks. 6 Further studies on antibiotic therapy are in progress.…”

“…There is no need to give additional antibiotics when the initial course has been completed as cultures are sterile, and there is no evidence that corticosteroid treatment is beneficial. 8,59,64 The immunological mechanism underpinning paradoxical reactions requires clearer elucidation in order to design appropriate evidencebased interventions for this important clinical phenomenon.…”

“…8 Despite antibiotic efficacy with healing of up to two-thirds of patients within 25 weeks after initiation of treatment, the time to healing differs significantly for similar-sized lesions, [9][10][11] and this is influenced by the quality of wound care. As ulcerative disease forms the majority of lesions in many treatment centers, [7][8][9]12 wound care plays a pivotal role in the care and treatment outcomes of patients. 13 In addition, as a result of late presentation to health facilities, scarring and contractures may complicate the healing process, particularly among patients who are not treated early, leading to long-term functional disability and occasionally amputation of affected limbs.…”