BackgroundParadoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.MethodsData was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.ResultsThirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p = 0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p < 0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p = 0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p < 0.01) were associated with an increased incidence of paradoxical reactions.ConclusionsParadoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

M. ulcerans infections are increasing in the Bellarine Peninsula. They usually present as single ulcerative lesions on limbs, commonly over joints. Age and sex influence clinical presentation, and PCR of lesions has high diagnostic sensitivity.

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Objective: To describe the effect of antibiotics on outcomes of treatment for Buruli or Bairnsdale ulcer (BU) in patients on the Bellarine Peninsula in south‐eastern Australia. Design: Observational, non‐randomised study with data collected prospectively or through medical record review. Patients and setting: All 40 patients with BU managed by staff of Barwon Health's Geelong Hospital (a public, secondary‐level hospital) between 1 January 1998 and 31 December 2004. Main outcome measures: Epidemiology, clinical presentation, diagnosis, treatment and clinical outcomes. Results: There were 59 treatment episodes; 29 involved surgery alone, 26 surgery plus antibiotics, and four antibiotics alone. Of 55 episodes where surgery was performed, minor surgery was required in 22, and major surgery in 33. Failure rates were 28% for surgery alone, and 19% for surgery plus antibiotics. Adjunctive antibiotic therapy was associated with increased treatment success for lesions with positive histological margins (P < 0.01), and lesions requiring major surgery for treatment of a first episode (P < 0.01). The combination of rifampicin and ciprofloxacin resulted in treatment success in eight of eight episodes, and no patients ceased therapy because of side effects with this regimen. Conclusions: Adjunctive antibiotic therapy may increase the effectiveness of BU surgical treatment, and this should be further assessed by larger randomised controlled trials. The combination of rifampicin and ciprofloxacin appears the most promising.

BackgroundThe World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia.Methodology/Principal FindingsAnalysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was 62 years (range 3–94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p<0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27–2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases.ConclusionsAntibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.