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INTRODUCTION: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. METHODS: The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. RESULTS: There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. DISCUSSION: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in thes

Researchers have hypothesized that mosquitoes are vectors involved in Mycobacterium ulcerans transmission. Previous findings of a correlation between incidence of M. ulcerans, which causes Buruli ulcer, and locally acquired vectorborne diseases in southeastern Australia further strengthened this argument. However, our updated data indicate that this correlation has not continued beyond 2008.

Despite the availability of evidence-based guidelines, antibiotics for cellulitis remain inappropriately prescribed. This evidence-practice gap is more evident in low-resource settings, such as rural hospitals. This implementation study developed and introduced a cellulitis management plan to improve antibiotic prescribing for cellulitis in three health services in regional Australia. Appropriateness of antibiotic prescribing for cellulitis at Day 1 was the primary outcome measure. Adults with ICD-10-AM codes for lower-limb cellulitis admitted as inpatients of the three health services between May and November 2019 (baseline, n = 165) and March and October 2020 (post-implementation, n = 127) were included in the assessment. The uptake of the cellulitis management plan was 29.1% (37/127). The appropriateness of antibiotic prescribing for cellulitis at Day 1 was similar at baseline (78.7%, 144/183) and in the intention-to-treat post-implementation group (81.8%, 126/154) [95% CI -5.6% to 11.3%, p = 0.50]. Commencement of the cellulitis management plan resulted in a non-statistically significant increase in antibiotic appropriateness at Day 1 compared to when a cellulitis management plan was not commenced (88.1% vs. 79.5%; 95% CI -5.6% to 19.8%; p = 0.20) Evaluation of more real-world strategies to address evidence-practice gaps, such as the appropriateness of antibiotic prescribing for cellulitis, is required.

OBJECTIVES: There have been efforts to promote timely antimicrobial administration for patients with sepsis, but the importance for other infections is uncertain. This study analysed whether time to first antimicrobial dose (TFAD) in patients with lower limb cellulitis influenced outcome measures such as acute length of stay (LOS) in hospital and 30-day hospital readmission rates for cellulitis. METHODS: Medical records of patients admitted with lower limb cellulitis or erysipelas over a 15-month period (1 May 2019 to 30 November 2019 and 1 March 2020 to 31 October 2020) were reviewed. Patients requiring intensive care unit (ICU) admission were excluded. The TFAD was the difference (in minutes) between the emergency department triage time and the time that the antimicrobial was first recorded as administered. Analysis included log-transformed linear regression (for LOS) and logistic regression (for 30-day readmission with cellulitis), controlling for confounders where possible. RESULTS: The study included 282 patients with lower limb cellulitis. The median TFAD was 177 min (interquartile range, 98-290 min). Linear regression suggested a weak association between TFAD and LOS (P = 0.05; adjusted R2 = 0.01), which was non-significant after adjusting for confounders (P = 0.18). There were too few patients readmitted within 30 days with cellulitis for meaningful analysis. CONCLUSION: After controlling for confounders, no association between increased TFAD and increased acute LOS was identified for patients with lower limb cellulitis who did not require ICU admission (i.e. without septic shock). Conclusions could not be made for 30-day readmission rates for cellulitis.

Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing 'big data' on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years.

BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. CASE PRESENTATIONS: Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. CONCLUSIONS: Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infect

BACKGROUND: Antimicrobial stewardship programmes are important in driving safety and quality of antimicrobial prescribing. The National Antimicrobial Prescribing Survey (NAPS) is a point-prevalence audit of inpatient antimicrobial prescribing in Australian hospitals. OBJECTIVES: To design and adapt the NAPS tool for use in the outpatient parenteral antimicrobial therapy (OPAT) and hospital-in-the-home (HITH) setting. METHODS: An inter-disciplinary working group with expertise in OPAT and HITH services was established to adapt the NAPS template for use in the OPAT setting-called HITH-NAPS. This was initially trialled in 5 HITH services, subsequently adapted following participant feedback, then offered nationally to 50 services in 2017. RESULTS: There were 1154 prescriptions for 715 patients audited via the HITH-NAPS. The most common antimicrobials prescribed were cefazolin (22%), flucloxacillin (12%), piperacillin/tazobactam (10%) and ceftriaxone (10%). The most common infections treated were cellulitis (30%) and respiratory tract infections (14%). Eighty-seven percent of prescriptions were assessed as appropriate, 11% inappropriate and 2% not assessable. Prolonged durations of antimicrobials and unnecessarily broad-spectrum antibiotics were used in 9% of prescriptions. CONCLUSIONS: The HITH-NAPS pilot project revealed that auditing of this type is feasible in HITH. It showed that antibiotic use in these HITH services was generally appropriate, but there are some areas for improvement. A national OPAT/HITH-NAPS can facilitate benchmarking between services, identify potentially inappropriate prescribing and help guide quality improvement.

OBJECTIVE: To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype-protein structure-phenotype relationships. METHODS: We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three-dimensional structural protein model. RESULTS: The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic. We attributed the same variant in two siblings to parental mosaicism. Patients initially presented with seizures beginning in the first 3 months of life (8/14), developmental delay (4/14), hypotonia (1/14), or movement disorder (1/14). All patients had hypotonia and developmental delay ranging from mild to severe. Nine had epilepsy, and nine had movement disorders, including dystonia, ataxia, chorea, and dyskinesia. The 13 GNAO1 variants in our patients are predicted to result in amino acid substitutions or deletions in the GNAO1 guanosine triphosphate (GTP)-binding region, analogous to those in previous publications. Patients with variants affecting amino acids 207-221 had only movement disorder and hypotonia. Patients with variants affecting the C-terminal region had the mildest phenotypes. SIGNIFICANCE: GNAO1 encephalopathy most frequently presents with seizures beginning in the first 3 months of life. Concurrent movement disorders are also a prominent feature in the spectrum of GNAO1 encephalopathy. All variants affected the GTP-binding domain of GNAO1, highlighting the importance of this region for G-protein signaling and neurodevelopment.

BACKGROUND: Diagnostic testing using polymerase chain reaction (PCR) is infrequently initiated for diagnosis of respiratory tract infections (RTIs) in nursing homes. The objectives of this study were to determine the feasibility of implementing nurse-initiated PCR testing of respiratory specimens in nursing home settings and to compare antibiotic prescribing prior to and during the implementation. METHODS: This was a pragmatic, historically controlled study in 3 nursing homes (181 total beds) in Melbourne, Australia. RESULTS: The number of PCR tests of respiratory specimens (over 12 months) increased from 5 to 67 when nurses could initiate the tests. Residents with RTI symptoms had a virus identified by PCR in 50.7% of tests, including 14 positive for influenza. Six outbreaks were identified. When clustering was taken into consideration, incidence rates of antibiotic days of therapy did not change (incidence rate ratio = 0.94, 95% confidence interval, 0.25-3.35, P = .92) despite identification of more viral pathogens. CONCLUSIONS: In nursing homes, nurse-initiated PCR testing of respiratory specimens is feasible and useful in terms of identifying the cause of many RTIs and outbreaks, and viruses are common in this context. However, the current study suggests the availability of these test results alone does not impact antibiotic prescribing.

With the demonstration of the effectiveness of antibiotic treatment, the management of Mycobacterium ulcerans disease has changed from a predominantly surgically to a predominantly medically treated disease. However, research among Australian patients has revealed that antibiotic treatment alone is associated with prolonged wound healing times, high rates of treatment toxicity, and the potential for significant tissue destruction associated with severe paradoxical reactions. We present the current state of M. ulcerans management in Barwon Health, Australia, where a close working relationship exists between the Plastic Surgical and Infectious Diseases units. Here treatment has evolved based on nearly 20 years of experience gained from managing more around 600 patients from a M. ulcerans epidemic on the nearby Bellarine and Mornington Peninsulas. In our experience, surgery has re-emerged to play an important role in the treatment of M. ulcerans in improving the rate of wound healing, minimizing antibiotic associated toxicity and preventing further tissue loss associated with severe paradoxical reactions. For selected small lesions surgery without antibiotics may also be an effective treatment option, however aggressive surgical resection of lesions with wide margins through uninvolved tissue should no longer be performed. Furthermore, extensive excisional surgery that will require the use of split skin grafts and vascularized tissue flaps to repair skin defects should be avoided if possible.

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 c

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, are urgently needed to improve the understanding of disease to facilitate implementation of effective public health measures to halt its spread.

We conducted epidemiologic and genetic analyses of family clusters of Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found that the incidence of M. ulcerans disease in family members was increased. However, the risk for exposure appeared short-term and not related to human-human transmission.

BACKGROUND: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is increasing in incidence in Victoria, Australia. To improve understanding of disease transmission, we aimed to map the location of BU lesions on the human body. METHODS: Using notification data and clinical records review, we conducted a retrospective observational study of patients diagnosed with BU in Victoria from 1998-2015. We created electronic density maps of lesion locations using spatial analysis software and compared lesion distribution by age, gender, presence of multiple lesions and month of infection. FINDINGS: We examined 579 patients with 649 lesions; 32 (5.5%) patients had multiple lesions. Lesions were predominantly located on lower (70.0%) and upper (27.1%) limbs, and showed a non-random distribution with strong predilection for the ankles, elbows and calves. When stratified by gender, upper limb lesions were more common (OR 1·97, 95% CI 1·38-2·82, p<0·001) while lower limb lesions were less common in men than in women (OR 0·48, 95% CI 0·34-0·68, p<0·001). Patients aged ≥ 65 years (OR 3·13, 95% CI 1·52-6·43, p = 0·001) and those with a lesion on the ankle (OR 2·49, 95% CI 1·14-5·43, p = 0·02) were more likely to have multiple lesions. Most infections (71.3%) were likely acquired in the warmer 6 months of the year. INTERPRETATION: Comparison with published work in Cameroon, Africa, showed similar lesion distribution and suggests the mode of M. ulcerans transmission may be the same across the globe. Our findings also aid clinical diagnosis and provide quantitative background information for further research investigating disease transmission.

OBJECTIVES: To investigate how patients prefer to be addressed by healthcare providers and to assess their knowledge of their attending medical team's identity in an Australian Hospital. SETTING: Single-centre, large tertiary hospital in Australia. PARTICIPANTS: 300 inpatients were included in the survey. Patients were selected in a sequential, systematic and whole-ward manner. Participants were excluded with significant cognitive impairment, non-English speaking, under the age of 18 years or were too acutely unwell to participate. The sample demographic was predominately an older population of Anglo-Saxon background. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients preferred mode of address from healthcare providers including first name, title and second name, abbreviated first name or another name. Whether patients disliked formal address of title and second name. Secondarily, patient knowledge of their attending medical team members name and role and if correct, what position within the medical hierarchy they held. RESULTS: Over 99% of patients prefer informal address with greater than one-third having a preference to being called a name other than their legal first name. 57% of patients were unable to correctly name a single member of their attending medical team. CONCLUSIONS: These findings support patient preference of informal address; however, healthcare providers cannot assume that a documented legal first name is preferred by the patient. Patient knowledge of their attending medical team is poor and suggests current introduction practices are insufficient.

BACKGROUND: The clinical presentation of M. ulcerans disease and the safety and effectiveness of treatment may differ in elderly compared with younger populations related to relative immune defficiencies, co-morbidities and drug interactions. However, elderly populations with M. ulcerans disease have not been comprehensively studied. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective analysis was performed on an observational cohort of all confirmed M. ulcerans cases managed at Barwon Health from 1/1/1998-31/12/2014. The cohort included 327 patients; 131(40.0%) ≥65 years and 196(60.0%) <65 years of age. Patients ≥65 years had a shorter median duration of symptoms prior to diagnosis (p<0.01), a higher proportion with diabetes (p<0.001) and immune suppression (p<0.001), and were more likely to have lesions that were multiple (OR 4.67, 95% CI 1.78-12.31, p<0.001) and WHO category 3 (OR 4.59, 95% CI 1.98-10.59, p<0.001). Antibiotic complications occurred in 69(24.3%) treatment episodes at an increased incidence in those aged ≥65 years (OR 5.29, 95% CI 2.81-9.98, p<0.001). There were 4(1.2%) deaths, with significantly more in the age-group ≥65 years (4 compared with 0 deaths, p = 0.01). The overall treatment success rate was 92.2%. For the age-group ≥65 years there was a reduced rate of treatment success overall (OR 0.34, 95% CI 0.14-0.80, p = <0.01) and when surgery was used alone (OR 0.21, 95% CI 0.06-0.76, p<0.01). Patients ≥65 years were more likely to have a paradoxical reaction (OR 2.06, 95% CI 1.17-3.62, p = 0.01). CONCLUSIONS/SIGNIFICANCE: Elderly patients comprise a significant proportion of M. ulcerans disease patients in Australian populations and present with more severe and advanced disease forms. Currently recommended treatments are associated with increased toxicity and reduced effectiveness in elderly populations. Increased efforts are required to diagnose M. ulcerans earlier in elderly populations, and research is urgently required to develop more effective

INTRODUCTION: Mycobacterium ulcerans (M. ulcerans) is a necrotizing skin infection endemic to the Bellarine Peninsula, Australia. Current treatment recommendations include 8 weeks of combination antibiotics, with adjuvant surgery if necessary. However, antibiotic toxicity often results in early treatment cessation and local experience suggests that shorter antibiotic courses may be effective with concurrent surgery. We report the outcomes of patients in the Barwon Health M. ulcerans cohort who received shorter courses of antibiotic therapy than 8 weeks. METHODOLOGY / PRINCIPAL FINDINGS: A retrospective analysis was performed of all M. ulcerans infections treated at Barwon Health from March 1, 1998 to July 31, 2013. Sixty-two patients, with a median age of 65 years, received < 56 days of antibiotics and 51 (82%) of these patients underwent concurrent surgical excision. Most received a two-drug regimen of rifampicin combined with either ciprofloxacin or clarithromycin for a median 29 days (IQR 21-41 days). Cessation rates were 55% for adverse events and 36% based on clinician decision. The overall success rate was 95% (98% with concurrent surgery; 82% with antibiotics alone) with a 50% success rate for those who received < 14 days of antibiotics increasing to 94% if they received 14-27 days and 100% for 28-55 days (p<0.01). A 100% success rate was seen for concurrent surgery and 14-27 days of antibiotics versus 67% for concurrent surgery and < 14 days of antibiotics (p = 0.12). No previously identified risk factors for treatment failure with surgery alone were associated with reduced treatment success rates with < 56 days of antibiotics. CONCLUSION: In selected patients, antibiotic treatment durations for M. ulcerans shorter than the current WHO recommended 8 weeks duration may be associated with successful outcomes.

BACKGROUND: Information about the feasibility, barriers and facilitators of antimicrobial stewardship (AMS) in residential aged care facilities (RACFs) has been scant. Exploring the prevailing perceptions and attitudes of key healthcare providers towards antibiotic prescribing behaviour, antibiotic resistance and AMS in the RACF setting is imperative to guide AMS interventions. METHODS: Semi-structured interviews and focus groups were conducted with key RACF healthcare providers until saturation of themes occurred. Participants were recruited using purposive and snowball sampling. The framework approach was applied for data analysis. RESULTS: A total of 40 nurses, 15 general practitioners (GPs) and 6 pharmacists from 12 RACFs were recruited. Five major themes emerged; perceptions of current antibiotic prescribing behaviour, perceptions of antibiotic resistance, attitude towards and understanding of AMS, perceived barriers to and facilitators of AMS implementation, and feasible AMS interventions. A higher proportion of GPs and pharmacists compared with nurses felt there was over-prescribing of antibiotics in the RACF setting. Antibiotic resistance was generally perceived as an issue for infection control rather than impacting clinical decisions. All key stakeholders were supportive of AMS implementation in RACFs; however, they recognized barriers related to workload and logistical issues. A range of practical AMS interventions were identified, with nursing-based education, aged-care specific antibiotic guidelines and regular antibiotic surveillance deemed most useful and feasible. CONCLUSIONS: Areas of antibiotic over-prescribing have been identified from different healthcare providers' perspectives. However, concern about the clinical impact of antibiotic resistance was generally lacking. Importantly, information gathered about feasibility, barriers and facilitators of various AMS interventions will provide important insights to guide development of AMS programs in

INTRODUCTION: Oedematous lesions are a less common but more severe form of Mycobacterium ulcerans disease. Misdiagnosis as bacterial cellulitis can lead to delays in treatment. We report the first comprehensive descriptions of the clinical features and risk factors of patients with oedematous disease from the Bellarine Peninsula of south-eastern Victoria, Australia. METHODS: Data on all confirmed Mycobacterium ulcerans cases managed at Barwon Health, Victoria, were collected from 1/1/1998-31/12/2012. A multivariate logistic regression model was used to assess associations with oedematous forms of Mycobacterium ulcerans disease. RESULTS: Seventeen of 238 (7%) patients had oedematous Mycobacterium ulcerans lesions. Their median age was 70 years (IQR 17-82 years) and 71% were male. Twenty-one percent of lesions were WHO category one, 35% category two and 41% category three. 16 (94%) patients were initially diagnosed with cellulitis and received a median 14 days (IQR 9-17 days) of antibiotics and 65% required hospitalization prior to Mycobacterium ulcerans diagnosis. Fever was present in 50% and pain in 87% of patients. The WCC, neutrophil count and CRP were elevated in 54%, 62% and 75% of cases respectively. The median duration of antibiotic treatment was 84 days (IQR 67-96) and 94% of cases required surgical intervention. On multivariable analysis, there was an increased likelihood of a lesion being oedematous if on the hand (OR 85.62, 95% CI 13.69-535.70; P<0.001), elbow (OR 7.83, 95% CI 1.39-43.96; p<0.001) or ankle (OR 7.92, 95% CI 1.28-49.16; p<0.001), or if the patient had diabetes mellitus (OR 9.42, 95% CI 1.62-54.74; p = 0.02). CONCLUSIONS: In an Australian population, oedematous Mycobacterium ulcerans lesions present with similar symptoms, signs and investigation results to, and are commonly mistakenly diagnosed for, bacterial limb cellulitis. There is an increased likelihood of oedematous lesions affecting the hand, elbow or ankle, and in patients with diabet

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons. © 2013 Cheng et al.

BACKGROUND: Mycobacterium ulcerans (MU) is responsible for disfiguring skin lesions and is endemic on the Bellarine peninsula of southeastern Australia. Antibiotics have been shown to be highly effective in sterilizing lesions and preventing disease recurrences when used alone or in combination with surgery. Our practice has evolved to using primarily oral medical therapy. METHODS: From a prospective cohort of MU patients managed at Barwon Health, we describe those treated with primary medical therapy defined as treatment of a M. ulcerans lesion with antimicrobials either alone or in conjunction with limited surgical debridement. RESULTS: From 1/10/2010 through 31/12/11, 43 patients were treated with exclusive medical therapy, of which 5 (12%) also underwent limited surgical debridement. The median patient age was 50.2 years, and 86% had WHO category 1 and 91% ulcerative lesions. Rifampicin was combined with ciprofloxacin in 30 (70%) and clarithromycin in 12 (28%) patients. The median duration of antibiotic therapy was 56 days, with 7 (16%) receiving less than 56 days. Medication side effects requiring cessation of one or more antibiotics occurred in 7 (16%) patients. Forty-two (98%) patients healed without recurrence within 12 months, and 1 patient (2%) experienced a relapse 4 months after completion of 8 weeks of antimicrobial therapy. CONCLUSION: Our experience demonstrates the efficacy and safety of primary oral medical management of MU infection with oral rifampicin-based regimens. Further research is required to determine the optimal and minimum durations of antibiotic therapy, and the most effective antibiotic dosages and formulations for young children.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.

BACKGROUND: Paradoxical 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. METHODS: Data 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. RESULTS: Thirty-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. CONCLUSIONS

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 antibioti