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Clinical Therapeutics

Risk Factors Associated with Antibiotic Treatment Failure of Buruli Ulcer

Daniel P. O’Brien, N. Deborah Friedman, Aaron Walton, Andrew Hughes, Eugene Athan
Daniel P. O’Brien
aBarwon Health, University Hospital Geelong, Geelong, Australia
bDepartment of Medicine and Infectious Diseases, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia
cGeelong Centre for Emerging Infectious Diseases, Geelong, Australia
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N. Deborah Friedman
aBarwon Health, University Hospital Geelong, Geelong, Australia
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Aaron Walton
aBarwon Health, University Hospital Geelong, Geelong, Australia
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Andrew Hughes
aBarwon Health, University Hospital Geelong, Geelong, Australia
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Eugene Athan
aBarwon Health, University Hospital Geelong, Geelong, Australia
dDeakin University, School of Medicine, Geelong, Australia
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DOI: 10.1128/AAC.00722-20
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ABSTRACT

Combination antibiotic therapy is highly effective in curing Buruli ulcer (BU) caused by Mycobacterium ulcerans. Treatment failures have been uncommonly reported with the recommended 56 days of antibiotics, and little is known about risk factors for treatment failure. We analyzed treatment failures among BU patients treated with ≥56 days of antibiotics from a prospective observational cohort at Barwon Health, Victoria, from 1 January 1998 to 31 December 2018. Treatment failure was defined as culture-positive recurrence within 12 months of commencing antibiotics under the following conditions: (i) following failure to heal the initial lesion or (ii) a new lesion developing at the original or at a new site. A total of 430 patients received ≥56 days of antibiotic therapy, with a median duration of 56 days (interquartile range [IQR], 56 to 80). Seven (1.6%) patients experienced treatment failure. For six adult patients experiencing treatment failure, all were male, weighed >90 kg, did not have surgery, and received combination rifampin-clarithromycin (median rifampin dose, 5.6 mg per kg of body weight per day; median clarithromycin dose, 8.1 mg/kg/day). When compared to those who did not fail treatment on univariate analysis, treatment failure was significantly associated with a weight of >90 kg (P < 0.001), male gender (P = 0.02), immune suppression (P = 0.04), and a first-line regimen of rifampin-clarithromycin compared to a regimen of rifampin-fluoroquinolone (P = 0.05). There is a low rate of treatment failure in Australian BU patients treated with rifampin-based oral combination antibiotic therapy. Our study raises the possibility that treatment failure risk may be increased in males, those with a body weight of >90 kg, those with immune suppression, and those taking rifampin-clarithromycin antibiotic regimens, but future pharmacokinetic and pharmacodynamics studies are required to determine the validity of these hypotheses.

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Risk Factors Associated with Antibiotic Treatment Failure of Buruli Ulcer
Daniel P. O’Brien, N. Deborah Friedman, Aaron Walton, Andrew Hughes, Eugene Athan
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00722-20; DOI: 10.1128/AAC.00722-20

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Risk Factors Associated with Antibiotic Treatment Failure of Buruli Ulcer
Daniel P. O’Brien, N. Deborah Friedman, Aaron Walton, Andrew Hughes, Eugene Athan
Antimicrobial Agents and Chemotherapy Aug 2020, 64 (9) e00722-20; DOI: 10.1128/AAC.00722-20
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KEYWORDS

Mycobacterium ulcerans
antibiotic
failure
risk factors
treatment

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