Risk factors associated with antibiotic treatment failure of buruli ulcer

O’Brien, DP, Deborah Friedman, N, Walton, A, Hughes, A and Athan, Eugene 2020, Risk factors associated with antibiotic treatment failure of buruli ulcer, Antimicrobial Agents and Chemotherapy, vol. 64, no. 9, pp. 1-9, doi: 10.1128/AAC.00722-20.


Title Risk factors associated with antibiotic treatment failure of buruli ulcer
Author(s) O’Brien, DP
Deborah Friedman, N
Walton, A
Hughes, A
Athan, EugeneORCID iD for Athan, Eugene orcid.org/0000-0001-9838-6471
Journal name Antimicrobial Agents and Chemotherapy
Volume number 64
Issue number 9
Start page 1
End page 9
Total pages 9
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2020-09-01
ISSN 0066-4804
1098-6596
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Microbiology
Pharmacology & Pharmacy
Mycobacterium ulcerans
antibiotic
failure
risk factors
treatment
MYCOBACTERIUM-ULCERANS
DRUG CONCENTRATIONS
IN-VITRO
RIFAMPIN
CLARITHROMYCIN
STREPTOMYCIN
PHARMACOKINETICS
CIPROFLOXACIN
RESISTANCE
INFECTION
Summary 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.
Language eng
DOI 10.1128/AAC.00722-20
Indigenous content off
Field of Research 0605 Microbiology
1108 Medical Microbiology
1115 Pharmacology and Pharmaceutical Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30139642

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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