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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/13365

Title: Kinetics of mycolactone in human subcutaneous tissue during antibiotic therapy for Mycobacterium ulcerans disease
Authors: Sarfo, Fred Stephen
Phillips, Richard Odame
Zhang, Jihui
Abass, Mohammed K.
Justice, Abotsi
Amoako, Yaw A.
Adu-Sarkodie, Yaw
Robinson, Clive
Wansbrough-Jones, Mark H.
Keywords: Mycobacterium ulcerans
Antibiotic therapy
Treatment response
Issue Date: 2014
Publisher: BMC Infectious Diseases
Citation: BMC Infectious Diseases 2014, 14:202; http://www.biomedcentral.com/1471-2334/14/202
Abstract: Background: Mycobacterium ulcerans (M. ulcerans) causes a devastating necrotising infection of skin tissue leading to progressive ulceration. M. ulcerans is the only human pathogen that secretes mycolactone, a polyketide molecule with potent cytotoxic and immunomodulatory properties. These unique features make mycolactone an attractive biomarker for M. ulcerans disease. We sought to measure the concentration of mycolactone within lesions of patients with Buruli ulcer before, during and after antibiotic treatment to evaluate its association with the clinical and bacteriological response to therapy. Methods: Biopsies of M. ulcerans infected skin lesions were obtained from patients before, during and after antibiotic therapy. Lipids were extracted from the biopsies and concentration of mycolactone was assayed by mass spectrometry and a cytotoxicity assay and correlated with clinical and bacteriological response to therapy. Results: Baseline concentration of mycolactone measured by mass spectrometry predicted time to complete healing of small nodules and ulcers. Even though intra-lesional concentrations of mycolactone declined with antibiotic treatment, the toxin was still present after antibiotic treatment for 6 weeks and also 4 weeks after the end of treatment for 8 weeks in a subgroup of patients with slowly healing lesions. Additionally viable bacilli were detected in a proportion of these slowly healing lesions during and after treatment. Conclusions: Our findings indicate that baseline intra-lesional mycolactone concentration and its kinetics with antibiotic therapy are important prognostic determinants of clinical and bacteriological response to antibiotic treatment for Mycobacterium ulcerans disease. Mycolactone may be a useful biomarker with potential utility in optimising antibiotic therapy.
Description: An article published by BMC Infectious Diseases 2014, 14:202; http://www.biomedcentral.com/1471-2334/14/202
URI: http://hdl.handle.net/123456789/13365
Appears in Collections:College of Health Sciences

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