Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia.

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.

Exploring the Preferences of the Australian Public for Antibiotic Treatments: A Discrete Choice Experiment.

OBJECTIVES: Identify Australian public preferences for antibiotic treatments in the context of antibiotic stewardship. METHODS: A discrete choice experiment (DCE) was conducted in Australia to investigate the importance of seven attributes associated with antibiotic treatments and related stewardship practices: contribution to antimicrobial resistance (AMR), treatment duration, side effects, days needed to recover, days before taking antibiotics, treatment failure and out-of-pocket costs. The DCE data were analysed using conditional logit, mixed logit and latent class conditional logit models. The relative importance of each attribute was calculated. RESULTS: A total of 1882 respondents completed the survey; the main study sample consist of 1658 respondents (mean age 48 years) who passed quality checks. All seven attributes significantly influenced respondents' preferences for antibiotic treatments. Based on the designed attribute levels in the DCE, on average, out-of-pocket costs (32.8%) and contribution to antibiotic resistance (30.3%) were the most important attributes, followed by side effects (12.9%). Days before starting medication was least important (3.9%). Three latent classes were identified. Class 1 (including respondents who were more likely to be older and more health literate; 24.5%) gave contribution to antibiotic resistance greater importance in treatment preferences. Class 2 (including respondents more likely to report poorer health; 25.2%) gave out-of-pocket costs greater importance. The remaining (50.4%), who were generally healthier, perceived side effects as the most important attribute. CONCLUSIONS: Despite concerted public awareness raising campaigns, our results suggest that several factors may influence the preferences of Australians when considering antibiotic use. However, for those more likely to be aware of the need to preserve antibiotics, out-of-pocket costs and limiting the contribution to antibiotic resistance are the dominant influence. Delays in starting treatment were not important for any latent class, suggesting public tolerance for this measure. These results could help inform strategies to promote prudent antibiotic stewardship.

The efficacy and safety of a shortened duration of antimicrobial therapy for group A Streptococcus bacteremia.

OBJECTIVES: To determine if shorter courses of antibiotic therapy for group A Streptococcus (GAS) bacteremia are associated with excess mortality. METHODS: In this retrospective study of consecutive cases of GAS bacteremia in tropical Australia, the duration of antibiotic therapy was correlated with 90-day all-cause mortality. RESULTS: There were 286 episodes of GAS bacteremia; the patients' median (interquartile range) age was 60 (48-71) years and 169/286 (59.1%) patients identified as an Indigenous Australian. There were 227/286 (79.4%) patients with a significant comorbidity. The all-cause 90-day mortality was 16/286 (5.6%); however, 12/16 (81.3%) patients died while still receiving their initial course of antibiotics and only 7/16 (43.8%) deaths were directly attributable to the GAS infection. After excluding patients who died while taking their initial course of antibiotics and those in whom the duration of therapy was uncertain, there was no difference in 90-day mortality between patients receiving ≤5 days of intravenous antibiotics and those receiving longer courses (1/137 [0.7%] vs 3/107 [2.8%], P-value = 0.32) nor in patients receiving ≤10 days of total therapy and those receiving longer courses (1/67 [1.5%] vs 3/178 [1.7%], P-value = 1.0). CONCLUSION: Even among patients with significant comorbidity, shorter antibiotic courses for GAS bacteremia are not associated with excess mortality.

How accurate is presumptive Chlamydia trachomatis treatment? A 6-month clinical audit of a walk-in sexual health service.

Background Chlamydia trachomatis (chlamydia) is highly prevalent and is an important sexually transmitted infection as it can lead to increased risk of HIV seroconversion; and if left untreated, can cause infertility in women. Clinical guidelines recommend treating chlamydia presumptively when presenting symptomatically; however, clinicians are now questioning this due to increasing prevalence of antimicrobial resistance. Methods To determine the accuracy of presumptive chlamydia treatment practices at a walk-in sexual health service in regional Australia, we audited all same-day screen and treat presentations prescribed azithromycin over a 6-month period in 2018. Results A total of 325 cases were included in the analysis. Over half (54%) the presentations returned negative pathology for all pathogens investigated. One quarter (25%) of presentations were positive for chlamydia, and (4%) reported a dual infection. A further one fifth (20%) were negative for chlamydia but positive for another pathogen. More symptomatic males than females returned positive pathology for chlamydia (8% vs 4%). Conclusions While presumptive treatment is recommended in the current guidelines, our findings indicate this resulted in over-treatment. Considering the increasing resistance patterns for Mycoplasma genitalium, which include azithromycin, presumptive treatments need to balance immediate client care needs against long-term community antimicrobial resistance outcomes. This internal audit provided a feedback mechanism to the walk-in sexual service, enabling modification of practices to provide more precise, individual clinical care within the bounds of current STI guidelines, while balancing wider the objectives of antimicrobial stewardship.

Antibiotic resistance in uropathogens across northern Australia 2007-20 and impact on treatment guidelines.

BACKGROUND: Urinary tract infections are common and are increasingly resistant to antibiotic therapy. Northern Australia is a sparsely populated region with limited access to healthcare, a relatively high burden of disease, a substantial regional and remote population, and high rates of antibiotic resistance in skin pathogens. OBJECTIVES: To explore trends in antibiotic resistance for common uropathogens Escherichia coli and Klebsiella pneumoniae in northern Australia, and how these relate to current treatment guidelines in the community and hospital settings. METHODS: We used data from an antibiotic resistance surveillance system. We calculated the monthly and yearly percentage of isolates that were resistant in each antibiotic class, by bacterium. We analysed resistance proportions geographically and temporally, stratifying by healthcare setting. Using simple linear regression, we investigated longitudinal trends in monthly resistance proportions and correlation between community and hospital isolates. RESULTS: Our analysis included 177 223 urinary isolates from four pathology providers between 2007 and 2020. Resistance to most studied antibiotics remained <20% (for E. coli and K. pneumoniae, respectively, in 2019: amoxicillin/clavulanate 16%, 5%; cefazolin 17%, 8%; nitrofurantoin 1%, 31%; trimethoprim 36%, 17%; gentamicin 7%, 2%; extended-spectrum cephalosporins 8%, 5%), but many are increasing by 1%-3% (absolute) per year. Patterns of resistance were similar between isolates from community and hospital patients. CONCLUSIONS: Antibiotic resistance in uropathogens is increasing in northern Australia, but treatment guidelines generally remain appropriate for empirical therapy of patients with suspected infection (except trimethoprim in some settings). Our findings demonstrate the importance of local surveillance data (HOTspots) to inform clinical decision making and guidelines.

Where to from here? Identifying and prioritising future directions for addressing drug-resistant infection in Australia.

BACKGROUND: The Australian National Antimicrobial Resistance Strategy calls for a collaborative effort to change practices that have contributed to the development of drug-resistance and for implementation of new initiatives to reduce antibiotic use. METHODS: A facilitated workshop was undertaken at the 2019 National Australian Antimicrobial Resistance Forum to explore the complexity of antimicrobial stewardship (AMS) implementation in Australia and prioritise future action. Participants engaged in rotating rounds of discussion using a world café format addressing six topics relating to AMS implementation. Once all tables had discussed all themes the discussion concluded and notes were summarised. The documents were independently openly coded by two researchers to identify elements relating to the implementation of antimicrobial stewardship. RESULTS: There were 39 participants in the facilitated discussions, including pharmacists, infectious disease physicians, infection prevention nurses, and others. Participants discussed strategies they had found successful, including having a regular presence in clinical areas, adapting messaging and implementation strategies for different disciplines, maintaining positivity, and being patient-focused. Many of the recommendations for the next step involved being patient focussed and outcomesdriven. This involves linking data to practice, using patient stories, using data to celebrate wins and creating incentives. DISCUSSION: Recommendations from the workshop should be included in priority setting for the implementation of AMS initiatives across Australia.

Antimicrobial stewardship in remote primary healthcare across northern Australia.

BACKGROUND: The high burden of infectious disease and associated antimicrobial use likely contribute to the emergence of antimicrobial resistance in remote Australian Aboriginal communities. We aimed to develop and apply context-specific tools to audit antimicrobial use in the remote primary healthcare setting. METHODS: We adapted the General Practice version of the National Antimicrobial Prescribing Survey (GP NAPS) tool to audit antimicrobial use over 2-3 weeks in 15 remote primary healthcare clinics across the Kimberley region of Western Australia (03/2018-06/2018), Top End of the Northern Territory (08/2017-09/2017) and far north Queensland (05/2018-06/2018). At each clinic we reviewed consecutive clinic presentations until 30 presentations where antimicrobials had been used were included in the audit. Data recorded included the antimicrobials used, indications and treating health professional. We assessed the appropriateness of antimicrobial use and functionality of the tool. RESULTS: We audited the use of 668 antimicrobials. Skin and soft tissue infections were the dominant treatment indications (WA: 35%; NT: 29%; QLD: 40%). Compared with other settings in Australia, narrow spectrum antimicrobials like benzathine benzylpenicillin were commonly given and the appropriateness of use was high (WA: 91%; NT: 82%; QLD: 65%). While the audit was informative, non-integration with practice software made the process manually intensive. CONCLUSIONS: Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems.

Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries.

BACKGROUND: Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies - pathogen whole genome sequencing (WGS) and Big Data analytics - promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy. METHOD: Four community juries were convened in two demographically different Sydney municipalities and two regional cities in New South Wales, Australia (western Sydney, Wollongong, Tamworth, eastern Sydney) to elicit the views of well-informed community members on the acceptability and legitimacy of: making pathogen WGS and linked administrative data available for public health researchusing this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts. RESULTS: Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems. CONCLUSIONS: Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.

Medical authority, managerial power and political will: A Bourdieusian analysis of antibiotics in the hospital.

Antibiotic resistance poses a significant global threat, yet clinically inappropriate antibiotic use within hospitals continues despite the implementation of abatement strategies. Antibiotic use and the viability of existing antibiotic options now sit precariously at the nexus of political will, institutional governance and clinical priorities 'at the bedside'. Yet no study has hitherto explored the perspectives of managers, instead of focusing on clinicians. In this article, drawing on qualitative interviews with hospital managers, we explore accounts of responding to antimicrobial resistance, managing antibiotic governance and negotiating clinical and managerial priorities. We argue that the managers' accounts articulate the problematic nexus of measurement and accountability, the downflow effects of political will, and core tensions within the hospital between moral, managerial and medical authority. We apply Bourdieu's theory of practice to argue that an understanding of the logics of practice within the 'hospital management classes' will be critical in efforts to protect antibiotics for future generations.

Sexual transmission of HIV and the law: an Australian medical consensus statement.

INTRODUCTION: Criminal cases involving human immunodeficiency virus transmission or exposure require that courts correctly comprehend the rapidly evolving science of HIV transmission and the impact of an HIV diagnosis. This consensus statement, written by leading HIV clinicians and scientists, provides current scientific evidence to facilitate just outcomes in Australian criminal cases involving HIV.Main recommendations: Caution should be exercised when considering charges or prosecutions regarding HIV transmission or exposure because:Scientific evidence shows that the risk of HIV transmission during sex between partners of different HIV serostatus can be low, negligible or too low to quantify, even when the HIV-positive partner is not taking effective antiretroviral therapy, depending on the nature of the sexual act, the viral load of the partner with HIV, and whether a condom or pre-exposure prophylaxis is employed to reduce risk.The use of phylogenetic analysis in cases of suspected HIV transmission requires careful consideration of its limited probative value as evidence of causation of HIV infection, although such an approach may provide valuable information, particularly in relation to excluding HIV transmission between individuals.Most people recently infected with HIV are able to commence simple treatment providing them a normal and healthy life expectancy, largely comparable with their HIV-negative peers. Among people who have been diagnosed and are receiving treatment, HIV is rarely life threatening. People with HIV can conceive children with negligible risk to their partner and low risk to their child.Changes in management as result of the consensus statement: Given the limited risk of HIV transmission per sexual act and the limited long term harms experienced by most people recently diagnosed with HIV, appropriate care should be taken before HIV prosecutions are pursued. Careful attention should be paid to the best scientific evidence on HIV risk and harms, with consideration given to alternatives to prosecution, including public health management.

Epidemiology and significance of coagulase-negative staphylococci isolated in blood cultures from critically ill adult patients.

BACKGROUND: Little published data are available on the epidemiology and significance of coagulase-negative staphylococci (CoNS) in blood culture isolates among critically ill adult patients. OBJECTIVES: To describe the epidemiology and frequency of CoNS blood culture isolates in critically ill adults, and investigate the association between time to positivity (TTP) of blood cultures and number of culture-positive bottles with organ dysfunction and mortality. DESIGN, SETTING AND PARTICIPANTS: A retrospective chart audit in the intensive care unit of a tertiary hospital comprising all patients who had positive blood cultures for CoNS in 2009. MAIN OUTCOME MEASURES: TTP, number of culture-positive bottles, Sequential Organ Failure Assessment (SOFA) scores, resolution of fever and white cell response and inotrope requirement, length of stay in ICU and mortality. RESULTS: In 2009, there were 1514 and 109 positive blood culture sets for the hospital and ICU patients, respectively. Of these, 515 sets from patients outside the ICU (34% of all hospital positive blood cultures) and 54 from the ICU (49.5% of all ICU positive blood cultures) were positive for CoNS. Patients with TTP ≤24 hours had higher organ failure scores by 0.9 (95% CI, 0-3.4; P = 0.052). There was a trend towards an association between increased 28-day mortality and TTP ≤24 hours (7/22 v 3/32; P = 0.071). There was no significant correlation between number of bottles positive for culture and mortality, length of stay, SOFA score, resolution of fever, white cell response, and inotrope requirement. CONCLUSIONS: Early TTP of blood cultures with CoNS may be associated with poorer outcome and may be a marker of true infection. Given the relatively high frequency of this microbiological problem, larger prospective observational studies are required to more clearly define the significance of a CoNS blood culture isolates in critically ill adult patients.