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    Comprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.
    McNamara, BJ ; Blasdell, KR ; Yerramilli, A ; Smith, IL ; Clayton, SL ; Dunn, M ; Tay, EL ; Gibney, KB ; Waidyatillake, NT ; Hussain, MA ; Muleme, M ; O'Brien, DP ; Athan, E (Centers for Disease Control and Prevention (CDC), 2023-10)
    To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.
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    Environmental risk factors associated with the presence of Mycobacterium ulcerans in Victoria, Australia
    Blasdell, KR ; McNamara, B ; O'Brien, DP ; Tachedjian, M ; Boyd, V ; Dunn, M ; Mee, PT ; Clayton, S ; Gaburro, J ; Smith, I ; Gibney, KB ; Tay, EL ; Hobbs, EC ; Waidyatillake, N ; Lynch, SE ; Stinear, TP ; Athan, E ; Becker, D (PUBLIC LIBRARY SCIENCE, 2022-09-13)
    In recent years reported cases of Buruli ulcer, caused by Mycobacterium ulcerans, have increased substantially in Victoria, Australia, with the epidemic also expanding geographically. To develop an understanding of how M. ulcerans circulates in the environment and transmits to humans we analyzed environmental samples collected from 115 properties of recent Buruli ulcer cases and from 115 postcode-matched control properties, for the presence of M. ulcerans. Environmental factors associated with increased odds of M. ulcerans presence at a property included certain native plant species and native vegetation in general, more alkaline soil, lower altitude, the presence of common ringtail possums (Pseudocheirus peregrinus) and overhead powerlines. However, only overhead powerlines and the absence of the native plant Melaleuca lanceolata were associated with Buruli ulcer case properties. Samples positive for M. ulcerans were more likely to be found at case properties and were associated with detections of M. ulcerans in ringtail possum feces, supporting the hypothesis that M. ulcerans is zoonotic, with ringtail possums the strongest reservoir host candidate. However, the disparity in environmental risk factors associated with M. ulcerans positive properties versus case properties indicates the involvement of human behavior or the influence of other environmental factors in disease acquisition that requires further study.
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    Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.
    Campbell, AJ ; Mowlaboccus, S ; Coombs, GW ; Daley, DA ; Al Yazidi, LS ; Phuong, LK ; Leung, C ; Best, EJ ; Webb, RH ; Voss, L ; Athan, E ; Britton, PN ; Bryant, PA ; Butters, CT ; Carapetis, JR ; Ching, NS ; Francis, J ; Hung, T-Y ; Nourse, C ; Ojaimi, S ; Tai, A ; Vasilunas, N ; McMullan, B ; Bowen, AC ; Blyth, CC ; Australian and New Zealand Pediatric Infectious Diseases (ANZPID) clinical research network (CRN) of the Australasian Society of Infectious Diseases (ASID) and the Australian Group on Antimicrobial Resistance (AGAR), (Elsevier BV, 2022-06)
    OBJECTIVES: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. METHODS: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. RESULTS: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]). CONCLUSION: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.
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    Pregnancy - a key moment for engaging women with hepatitis B in care
    Roder, C ; Chand, S ; Streat, S ; Beynon, S ; Huning, E ; Dabkowski, P ; Athan, E ; Wade, AJ (WILEY, 2021-06)
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    Predictors of Treatment Success After Periprosthetic Joint Infection: 24-Month Follow up From a Multicenter Prospective Observational Cohort Study of 653 Patients
    Davis, JS ; Metcalf, S ; Clark, B ; Robinson, JO ; Huggan, P ; Luey, C ; McBride, S ; Aboltins, C ; Nelson, R ; Campbell, D ; Solomon, LB ; Schneider, K ; Loewenthal, MR ; Yates, P ; Athan, E ; Cooper, D ; Rad, B ; Allworth, T ; Reid, A ; Read, K ; Leung, P ; Sud, A ; Nagendra, V ; Chean, R ; Lemoh, C ; Mutalima, N ; Tran, T ; Grimwade, K ; Sehu, M ; Looke, D ; Torda, A ; Aung, T ; Graves, S ; Paterson, DL ; Manning, L (OXFORD UNIV PRESS INC, 2022-03-01)
    BACKGROUND: Periprosthetic joint infection (PJI) is a devastating condition and there is a lack of evidence to guide its management. We hypothesized that treatment success is independently associated with modifiable variables in surgical and antibiotic management. METHODS: The is a prospective, observational study at 27 hospitals across Australia and New Zealand. Newly diagnosed large joint PJIs were eligible. Data were collected at baseline and at 3, 12, and 24 months. The main outcome measures at 24 months were clinical cure (defined as all of the following: alive, absence of clinical or microbiological evidence of infection, and not requiring ongoing antibiotic therapy) and treatment success (clinical cure plus index prosthesis still in place). RESULTS: Twenty-four-month outcome data were available for 653 patients. Overall, 449 patients (69%) experienced clinical cure and 350 (54%) had treatment success. The most common treatment strategy was debridement and implant retention (DAIR), with success rates highest in early postimplant infections (119 of 160, 74%) and lower in late acute (132 of 267, 49%) and chronic (63 of 142, 44%) infections. Selected comorbidities, knee joint, and Staphylococcus aureus infections were independently associated with treatment failure, but antibiotic choice and duration (including rifampicin use) and extent of debridement were not. CONCLUSIONS: Treatment success in PJI is associated with (1) selecting the appropriate treatment strategy and (2) nonmodifiable patient and infection factors. Interdisciplinary decision making that matches an individual patient to an appropriate management strategy is a critical step for PJI management. Randomized controlled trials are needed to determine the role of rifampicin in patients managed with DAIR and the optimal surgical strategy for late-acute PJI.
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    Correlation between Buruli Ulcer Incidence and Vectorborne Diseases, Southeastern Australia, 2000-2020
    Linke, JA ; Athan, E ; Friedman, ND (CENTERS DISEASE CONTROL & PREVENTION, 2021-12)
    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.
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    The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study
    Chiong, F ; Wasef, MS ; Liew, KC ; Cowan, R ; Tsai, D ; Lee, YP ; Croft, L ; Harris, O ; Gwini, SM ; Athan, E (BMC, 2021-07-09)
    BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB. METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality. RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups. CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.
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    C-reactive protein predicts complications in community-associated S. aureus bacteraemia: a cohort study
    Botheras, CL ; Bowe, SJ ; Cowan, R ; Athan, E (BMC, 2021-04-01)
    BACKGROUND: Staphylococcus aureus (S. aureus) bacteraemia is increasingly acquired from community settings and is associated with a mortality rate of up to 40% following complications. Identifying risk factors for complicated S. aureus bacteraemia would aid clinicians in targeting patients that benefit from expedited investigations and escalated care. METHODS: In this prospective observational cohort study, we aimed to identify risk factors associated with a complicated infection in community-onset S. aureus bacteraemia. Potential risk factors were collected from electronic medical records and included: - patient demographics, symptomology, portal of entry, and laboratory results. RESULTS: We identified several potential risk factors using univariate analysis. In a multiple logistic regression model, age, haemodialysis, and entry point from a diabetic foot ulcer were all significantly protective against complications. Conversely, an unknown entry point of infection, an entry point from an indwelling medical device, and a C-reactive protein concentration of over 161 mg/L on the day of admission were all significantly associated with complications. CONCLUSIONS: We conclude that several factors are associated with complications including already conducted laboratory investigations and portal of entry of infection. These factors could aid the triage of at-risk patients for complications of S. aureus bacteraemia.
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    The effectiveness of a simple antimicrobial stewardship intervention in general practice in Australia: a pilot study
    Neels, AJ ; Bloch, AE ; Gwini, SM ; Athan, E (BMC, 2020-08-07)
    BACKGROUND: Inappropriate and excessive antimicrobial prescribing can lead to antimicrobial resistance. Antimicrobial Stewardship (AMS) principles are not well established in general practice in Australia despite the relatively high rate of community antimicrobial prescribing. Few interventions have been implemented that have resulted in a significant reduction or improvement in antimicrobial prescribing by General Practitioners (GPs). This study was therefore conducted to assess the impact of a novel GP educational intervention on the appropriateness of antimicrobial prescriptions as well as GP compliance with antimicrobial prescription guidelines. METHODS: In 2018, a simple GP educational intervention was rolled out in a large clinic with the aim of improving antimicrobial prescribing. It included face-to-face education sessions with GPs on AMS principles, antimicrobial resistance, current prescribing guidelines and microbiological testing. An antibiotic appropriateness audit on prescribing practice before and after the educational intervention was conducted. Data were summarised using percentages and compared across time points using Chi-squared tests and Poisson regression (results reported as risk ratios (RR) with 95% confidence intervals (CI)). RESULTS: Data from 376 and 369 prescriptions in July 2016 and July 2018, respectively, were extracted. There were significant improvements in appropriate antimicrobial selection (73.9% vs 92.8%, RR = 1.26; 95% CI = 1.18-1.34), appropriate duration (53.1% vs 87.7%, RR = 1.65; 95% CI = 1.49-1.83) and compliance with guidelines (42.2% vs 58.5%, RR = 1.39, 95% CI = 1.19-1.61) post- intervention. Documentation of antimicrobial duration directions, patient follow-up as well as patient weight significantly increased after the intervention (p < 0.001). There was significant reduction in; prescriptions without a listed indication for antimicrobial therapy, prescriptions without appropriate accompanying microbiological tests and the provision of unnecessary repeat prescriptions (p < 0.001). Inappropriate antimicrobial prescriptions observed pre-intervention for medical termination of pregnancy ceased post-intervention. CONCLUSIONS: Auditing GP antimicrobial prescriptions identified prescribing practices inconsistent with Australian guidelines. However, implementation of a simple education program led to significantly improved antimicrobial prescribing by GPs. These findings indicate the important role of AMS and continued antimicrobial education within general practice.
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    Clinical Characteristics, Etiology, and Initial Management Strategy of Newly Diagnosed Periprosthetic Joint Infection: A Multicenter, Prospective Observational Cohort Study of 783 Patients
    Manning, L ; Metcalf, S ; Clark, B ; Robinson, JO ; Huggan, P ; Luey, C ; McBride, S ; Aboltins, C ; Nelson, R ; Campbell, D ; Solomon, LB ; Schneider, K ; Loewenthal, M ; Yates, P ; Athan, E ; Cooper, D ; Rad, B ; Allworth, T ; Reid, A ; Read, K ; Leung, P ; Sud, A ; Nagendra, V ; Chean, R ; Lemoh, C ; Mutalima, N ; Grimwade, K ; Sehu, M ; Torda, A ; Aung, T ; Graves, S ; Paterson, D ; Davis, J (OXFORD UNIV PRESS INC, 2020-05)
    BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Most observational studies of PJI are retrospective or single-center, and reported management approaches and outcomes vary widely. We hypothesized that there would be substantial heterogeneity in PJI management and that most PJIs would present as late acute infections occurring as a consequence of bloodstream infections. METHODS: The Prosthetic joint Infection in Australia and New Zealand, Observational (PIANO) study is a prospective study at 27 hospitals. From July 2014 through December 2017, we enrolled all adults with a newly diagnosed PJI of a large joint. We collected data on demographics, microbiology, and surgical and antibiotic management over the first 3 months postpresentation. RESULTS: We enrolled 783 patients (427 knee, 323 hip, 25 shoulder, 6 elbow, and 2 ankle). The mode of presentation was late acute (>30 days postimplantation and <7 days of symptoms; 351, 45%), followed by early (≤30 days postimplantation; 196, 25%) and chronic (>30 days postimplantation with ≥30 days of symptoms; 148, 19%). Debridement, antibiotics, irrigation, and implant retention constituted the commonest initial management approach (565, 72%), but debridement was moderate or less in 142 (25%) and the polyethylene liner was not exchanged in 104 (23%). CONCLUSIONS: In contrast to most studies, late acute infection was the most common mode of presentation, likely reflecting hematogenous seeding. Management was heterogeneous, reflecting the poor evidence base and the need for randomized controlled trials.