Aaron Walton

Epidemiology, clinical features and diagnosis of Mycobacterium ulcerans in an Australian population.

Objective: To describe the epidemiology, clinical features and diagnosis of Mycobacterium ulcerans infection occurring on the Bellarine Peninsula in Victoria.

Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study.

Background The 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 Findings Analysis 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. Conclusions Antibiotics 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.

Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections.

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.

Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort

Objective: To describe risk factors for recurrence after exclusive surgical treatment of Mycobacterium ulcerans infection.

Carbapenem-Resistant Enterobacteriaceae : A Strategic Roadmap for Infection Control

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has increased worldwide with great regional variability. Infections caused by these organisms are associated with crude mortality rates of up to 70%. The spread of CRE in healthcare settings is both an important medical problem and a major global public health threat. All countries are at risk of falling victim to the emergence of CRE; therefore, a preparedness plan is required to avoid the catastrophic natural course of this epidemic. Proactive and adequate preventive measures locally, regionally, and nationally are required to contain the spread of these bacteria. The keys to success in preventing the establishment of CRE endemicity in a region are early detection through targeted laboratory protocols and containment of spread through comprehensive infection control measures. This guideline provides a strategic roadmap for infection control measures based on the best available evidence and expert opinion, to enable preparation of a multifaceted preparedness plan to abort epidemics of CRE. Infect Control Hosp Epidemiol 2017;38:580-594.

Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort

ABSTRACT Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic-associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU.

The effectiveness of a single-stage versus traditional three-staged protocol of hospital disinfection at eradicating vancomycin-resistant Enterococci from frequently touched surfaces

BACKGROUND Environmental contamination is a reservoir for vancomycin-resistant enterococcus (VRE) in hospitals. METHODS Environmental sampling of surfaces was undertaken anytime before disinfection and 1 hour after disinfection utilizing a sodium dichloroisocyanurate-based, 3-staged protocol (phase 1) or benzalkonium chloride-based, single-stage clean (phase 2). VRE colonization and infection rates are presented from 2010 to 2011, and audits of cleaning completeness were also analyzed. RESULTS Environmental samples collected before disinfection were significantly more likely to be contaminated with VRE during phase 1 than phase 2: 25.2% versus 4.6%, respectively; odds ratio (OR), 7.01 (P < .01). Environmental samples collected after disinfection were also significantly more likely to yield VRE during phase 1 compared with phase 2: 11.2% versus 1.1%, respectively; OR, 11.73 (P < .01). Rates of VRE colonization were higher during 2010 than 2011. Cleaning audits showed similar results over both time periods. CONCLUSION During use of a chlorine-based, 3-staged protocol, significantly higher residual levels of VRE contamination were identified, compared with levels detected during use of a benzalkonium chloride-based product for disinfection. This reduction in VRE may be due to a new disinfection product, more attention to the thoroughness of cleaning, or other supplementary efforts in our institution.

Increased Severity and Spread of Mycobacterium ulcerans, Southeastern Australia

Reported cases of Mycobacterium ulcerans disease (Buruli ulcer) have been increasing in southeastern Australia and spreading into new geographic areas. We analyzed 426 cases of M. ulcerans disease during January 1998–May 2017 in the established disease-endemic region of the Bellarine Peninsula and the emerging endemic region of the Mornington Peninsula. A total of 20.4% of cases patients had severe disease. Over time, there has been an increase in the number of cases managed per year and the proportion associated with severe disease. Risk factors associated with severe disease included age, time period (range of years of diagnosis), and location of lesions over a joint. We highlight the changing epidemiology and pathogenicity of M. ulcerans disease in Australia. Further research, including genomic studies of emergent strains with increased pathogenicity, is urgently needed to improve the understanding of this disease to facilitate implementation of effective public health measures to halt its spread.

Wound healing: Natural history and risk factors for delay in Australian patients treated with antibiotics for Mycobacterium ulcerans disease

Background Healing times following treatment with antibiotics, and factors that influence healing, have not been reported in Australian patients with Mycobacterium ulcerans. Methodology/Principal findings Healing times were determined for all M. ulcerans cases treated by a single physician with antibiotics at Barwon Health, Victoria, from 1/1/13-31/12/16. Lesions were categorised by induration size: category A ≤ 400mm2, Category B 401-1600mm2 and Category C ≥1601mm2. A logistic regression analysis was performed to determine risk factors for prolonged wound healing (>150 days from antibiotic commencement). 163 patients were included; 92 (56.4%) were male and median age was 58 years (IQR 39–73 years). Baseline lesion size [available in 145 (89.0%) patients] was categorised as A in 46 (31.7%), B in 67 (46.2%) and C in 32 (22.1%) patients. Fifty (30.7%) patients had surgery. In those treated with antibiotics alone, 83.0% experienced a reduction in induration size after 2 weeks, then 70.9% experienced an increase in induration size from the lowest point, and 71.7% experienced an increase in ulceration size. A linear relationship existed between the time induration resolved and wound healing began. Median time to heal was 91 days (IQR 70–148 days) for category A lesions; significantly shorter than for category B lesions (128 days, IQR 91–181 days, p = 0.05) and category C lesions (169 days, IQR 159–214 days, p<0.001). Fifty-seven (35.0%) patients experienced a paradoxical reaction. Of those treated with antibiotics alone, lesions experiencing a paradoxical reaction had longer healing times [median time to heal 177 days (IQR 154–224 days) compared to 107 days (IQR 79–153 days), p<0.001]. On multivariable logistic regression, lesion size at baseline (p<0.001) and paradoxical reactions (p<0.001) were independently associated with prolonged healing times. For category A and B lesions, healing time was significantly shorter with antibiotics plus excision and direct closure compared with antibiotics alone [Category A lesions median 55 days (IQR 21–63 days) compared with 91 days (IQR 70–148 days), p<0.001; Category B lesions median 74 days (IQR 21–121 days) compared to 128 days (IQR 97–181 days), p<0.001]. Conclusions In Australian patients treated with antibiotics M. ulcerans lesions usually initially improve, then clinically deteriorate with increased induration and ulceration, before healing after the inflammation associated with lesions resolves. The time to complete healing of lesions is generally long, and is further prolonged in those with larger initial lesion size or who develop paradoxical reactions. For small lesions (<4cm2), excisional surgery may reduce healing times.

Antibiotic complications during the treatment of Mycobacterium ulcerans disease in Australian patients

Antibiotics are the recommended first‐line treatment for Mycobacterium ulcerans disease. Antibiotic toxicity is common in Australian patients, yet antibiotic complication rates and their risk factors have not been determined.