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Background This systematic review had 2 aims. First to identify the incidence of urinary tract infection (UTI) and bacteriuria in people undertaking intermittent catheterization (IC), second to determine the effectiveness of antiseptic cleaning of the meatal area prior to IC in reducing the incidence of UTI and bacteriuria. Methods A systematic review was conducted. Medline and the Cumulative Index to Nursing and Allied Health Literature electronic databases were systematically searched between January 1, 1990 and January 31, 2020, to identify studies that reported either the incidence of UTI or bacteriuria or the impact of using antiseptics for meatal cleaning prior to IC on incidence of these same outcomes. Results Twenty-five articles were identified for the first aim, 2 articles for the second. The proportion of participants experiencing ≥1 UTIs per year ranged from 15.4% to 86.6%. Synthesis of these studies suggest a combined incidence of 44.2% (95%CI 40.2%-48.5%) of participants having ≥1 UTIs per year. One of the 2 studies exploring the benefit of antiseptics in reducing UTI suggest some potential benefit of using chlorhexidine in reducing UTIs. Both studies have significant limitations, making interpretation difficult. Conclusions A large proportion of people undertaking IC in the community have UTIs each year. Evidence on the role of antiseptics in the prevention of UTI for people who undertake IC remains unclear.

In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia.

Background: Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab. Methods: This observational, dose-finding study was done in a clinical trials facility in Melbourne (VIC, Australia). Groups of healthy volunteers aged 18–40 years, at low risk of complicated S pyogenes disease, and without high type-specific anti-emm75 IgG antibodies against the challenge strain were challenged and closely monitored as inpatients for up to 6 days, and then as outpatients for 6 months. Antibiotics were started upon diagnosis (clinical signs and symptoms of pharyngitis and a positive rapid molecular test) or after 5 days in those without pharyngitis. Rapid test results were confirmed by standard bacterial culture. After a sentinel participant, cohorts of five and then ten participants were challenged, with protocol-directed dose-escalation or de-escalation for subsequent cohorts. The primary outcome was the proportion of participants at each dose level with pharyngitis by day 5 after challenge. The study is registered with ClinicalTrials.gov, NCT03361163. Findings: Between July 10, 2018, and Sept 23, 2019, 25 healthy adults were challenged with emm75 S pyogenes and included in analyses. Pharyngitis was diagnosed in 17 (85%; 95% CI 62–97) of 20 participants at the starting dose level (1–3 × 105 colony-forming units [CFU]/mL). This high proportion prompted dose de-escalation. At the lower dose level (1–3 × 104 CFU/mL), pharyngitis was diagnosed in one of five participants. Immunological, biochemical, and microbiological results supported the clinical picture, with acute symptomatic pharyngitis characterised by pharyngeal colonisation by S pyogenes accompanied by significantly elevated C-reactive protein and inflammatory cytokines (eg, interferon-γ and interleukin-6), and modest serological responses to streptolysin O and deoxyribonuclease B. There were no severe (grade 3) or serious adverse events related to challenge. Interpretation: We have established a reliable pharyngitis human infection model with reassuring early safety findings to accelerate development of vaccines and other interventions to control disease due to S pyogenes. Funding: Australian National Health and Medical Research Council., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? Methods Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. Findings At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). Conclusions Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

Background ICU-specific tables of antimicrobial susceptibility for key microbial species (‘antibiograms’), antimicrobial stewardship (AMS) programmes and routine rounds by infectious diseases (ID) physicians are processes aimed at improving patient care. Their impact on patient-centred outcomes in Australian and New Zealand ICUs is uncertain. Objectives To measure the association of these processes in ICU with in-hospital mortality. Methods The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database and Critical Care Resources registry were used to extract patient-level factors, ICU-level factors and the year in which each process took place. Descriptive statistics and hierarchical logistic regression were used to determine the relationship between each process and in-hospital mortality. Results The study included 799 901 adults admitted to 173 ICUs from July 2009 to June 2016. The proportion of patients exposed to each process of care was 38.7% (antibiograms), 77.5% (AMS programmes) and 74.0% (ID rounds). After adjusting for confounders, patients admitted to ICUs that used ICU-specific antibiograms had a lower risk of in-hospital mortality [OR 0.95 (99% CI 0.92–0.99), P = 0.001]. There was no association between the use of AMS programmes [OR 0.98 (99% CI 0.94–1.02), P = 0.16] or routine rounds with ID physicians [OR 0.96 (99% CI 0.09–1.02), P = 0.09] and in-hospital mortality. Conclusions Use of ICU-specific antibiograms was associated with lower in-hospital mortality for patients admitted to ICU. For hospitals that do not perform ICU-specific antibiograms, their implementation presents a low-risk infection management process that might improve patient outcomes.

Antimicrobial stewardship (AMS) is well established in Australian hospitals. Electronic medical record (EMR) implementation has lagged in Australia, with two Healthcare Information and Management Systems Society (HIMSS) Stage 6 hospitals and one Stage 7 hospital as of September 2020. Specific barriers faced by AMS teams with paper-based prescribing and medical records include real-time identification of antimicrobials orders; the ability to prospectively monitor antimicrobial use; and the integration of fundamental point of prescribing AMS principles into routine clinical practice. There are few local guidelines to assist Australian hospitals and AMS teams beyond “out of the box” EMR functionality. EMR implementation has enormous potential to positively impact AMS teams through more efficient workflows and the ability to expand the reach and coverage of AMS activities. There are inevitable limitations associated with EMR implementation that must be considered. In this paper, four Australian hospitals share their experience with EMR roll out, AMS customisation and how they have overcome specific barriers in local AMS practice.

The ability of health systems to cope with coronavirus disease (COVID-19) cases is of major concern. In preparation, we used clinical pathway models to estimate healthcare requirements for COVID-19 patients in the context of broader public health measures in Australia. An age- and risk-stratified transmission model of COVID-19 demonstrated that an unmitigated epidemic would dramatically exceed the capacity of the health system of Australia over a prolonged period. Case isolation and contact quarantine alone are insufficient to constrain healthcare needs within feasible levels of expansion of health sector capacity. Overlaid social restrictions must be applied over the course of the epidemic to ensure systems do not become overwhelmed and essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed, along with ongoing strengthening of capacity.

Evidence on the effectiveness of influenza vaccine in preventing antibiotic prescriptions for influenza-like illness (ILI) in adults is limited.A primary care-based case-control study was conducted to estimate influenza vaccine effectiveness (VE) against influenza-like illness (ILI) and antibiotic prescribing for ILI in adults aged ≥40 years. Cases were patients diagnosed with ILI from 1The number of ILI cases varied from 558 in 2018 to 2901 in 2017 and controls from 86618 in 2015 to 136763 in 2017. Over 4 years the pooled estimate of VE was 24% (95%CI, 11% to 34%) against ILI and 15% (95%CI, -3% to 29%) against antibiotic prescription for ILI. Influenza vaccine was effective in reducing ILI with an associated antibiotic prescriptions in patients aged65 years (VE=23%, 95%CI, 3% to 38%) and if no comorbidities were recorded (VE=22%, 95%CI, 1% to 39%) but not in other subgroups.Influenza vaccine reduced the likelihood of antibiotic prescriptions for ILI in low-risk adults (40-64 years and those without comorbidities).

Background The increasing availability of electronic healthcare data offers an opportunity to enhance adverse events following immunisation (AEFI) signal monitoring in near real-time. Aim To evaluate the potential use of telephone helpline data to augment the existing AEFI surveillance system in Victoria, Australia. Methods Anonymised telephone helpline call data were extracted between 2009 and 2017. For comparison, we included AEFI reports to the Victorian enhanced passive surveillance system, SAEFVIC-“Surveillance of Adverse Events Following Vaccination In the Community”. The temporal pattern cross-correlation coefficient at different time lags was estimated as a measure of timeliness evaluation. Historically known AEFI signals in 2010 and 2015 were examined using the Farrington statistical signal detection algorithm. Result During the study period, overall, the telephone helpline centre received 2,005,226 calls. Of these, 0.68% (13,719) were AEFI-related. In the same period, SAEFVIC received 10,367 AEFI related reports. Cross-correlation analysis, generally, showed that the two datasets were moderately correlated (r = 0.4) at a negative lag of 1 week. For individual years, the cross-correlation coefficient was highest (r = 0.66) in 2010 with the telephone helpline data leading by 2 weeks. Our analysis indicated the 2010 reported incidence of febrile convulsions and the 2015 reported increased allergic-related reactions following seasonal influenza vaccination three weeks and one week earlier respectively. Conclusion Telephone helpline data was able to detect an increased rate of AEFI earlier than the enhanced passive AEFI surveillance system. This dataset offers a valuable and near real-time component of an integrated AEFI early signal detection system in Australia.

INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.

Consumption of unsafe drinking water contributes to the global disease burden, necessitating identification and implementation of effective, acceptable, and sustainable water interventions in resource-limited settings. In a quantitative stepped-wedge cluster randomized trial of a community-based water intervention in rural India, we identified low rates of intervention uptake and reported diarrhea. To better understand and explain these findings, we performed a qualitative study examining barriers and enablers to intervention uptake and health reporting using the COM-B model, where capabilities, opportunities, and motivators interact to generate behavior. We conducted 20 focus groups and one semi-structured interview with participants and four focus groups with data collectors. Multifactorial barriers to intervention uptake included distorted perceptions of water-related health effects, implementation issues that reduced treated water availability; convenience of, and preference for, alternative drinking water sources; delivery of water to plastic storage tanks (perceived as affecting water quality and taste); and resistance to change. Enablers included knowledge of water-related health risks, proximity to tanks, and social opportunity. Barriers to health reporting included variability in interpretation of illness, suspicion regarding the consequences of reporting disease, weariness with repeated questions, and perceived inaction on health data already provided; low survey implementation fidelity was also important. Enablers included surveyor initiatives to encourage reporting and a sense of social responsibility. This qualitative explanatory study allowed better understanding of our quantitative results. It also identified obstacles and facilitators to implementing and evaluating community water interventions, providing insight on how to achieve better intervention uptake and health reporting in future studies.

Sustainable and low-cost methods for delivery of safe drinking water in resource-limited settings remain suboptimal, which contributes to global diarrhea morbidity. We aimed to assess whether delivery of riverbank filtration-treated water to newly installed water storage tanks (improved quality and access, intervention condition) reduced reported diarrhea in comparison to delivery of unfiltered river water (improved access alone, control condition) in rural Indian villages. We used a stepped wedge cluster-randomized trial (SW-CRT) design involving four clusters (villages). Selection criteria included village size, proximity to a river, and lack of existing or planned community-level safe water sources. All adults and children were eligible for enrollment. All villages started in the control condition and were sequentially randomized to receive the intervention at 3-month intervals. Our primary outcome was 7-day-period prevalence of self- or caregiver-reported diarrhea, measured at 3-month intervals (five time points). Analysis was by intention to treat. Because blinding was not possible, we incorporated questions about symptoms unrelated to water consumption to check response validity (negative control symptoms). We measured outcomes in 2,222 households (9,836 participants). We did not find a measurable reduction in diarrhea post-intervention (RR: 0.98 [95% CI: 0.24-4.09]); possible explanations include low intervention uptake, availability of other safe water sources, low baseline diarrheal prevalence, and reporting fatigue. Our study highlights both the difficulties in evaluating the impact of real-world interventions and the potential for an optimized SW-CRT design to address budgetary, funding, and logistical constraints inherent in such evaluations.

Background Sepsis is a medical emergency; timely management has been shown to reduce mortality. We aimed to improve the care of inpatients who developed sepsis after hospital admission by integrating a sepsis bundle with an existing medical emergency team (MET). Methods We performed a before-and-after study at an Australian institution. A multimodal intervention was implemented including formation of a working group, development of a guideline, standard documentation, education, audit and feedback. The primary outcome was the proportion of MET calls where there was compliance with the sepsis resuscitation bundle within one hour of MET call. Results There was an improvement in completion of the entire resuscitation bundle (OR 2.33, 95%, CI: 1.23 – 4.41) and lactate measurement (OR 2.72, CI: 1.53, 4.84) within one hour of MET call. There was a non-significant reduction in the median time to antibiotic administration in patients where antibiotics were initiated or changed at the MET call (60 mins vs. 44 mins, p=0.8). In hospital mortality was observed to fall from 22.1% to 11.4%, but after adjusting for age and baseline illness severity this differences was not statistically significant (OR 0.52, CI: 0.23, 1.19, p=0.12). Conclusion The implementation of a multimodal sepsis bundle and the utilisation of an existing MET call system demonstrated an increase in the overall uptake of a sepsis bundle. This was associated with an observed reduction in all-cause in-hospital mortality, although this difference was not statistically significant after adjustment for confounders. Further interventions with a focus on nursing education and engagement may improve timely antibiotic administration.

Positron emission tomography (PET) imaging necessitates the use of multidose vials for radiopharmaceutical delivery to patients. Conventional practices involve manual extraction of radiopharmaceuticals from a multidose vial prior to each PET procedure, which exposes the technologist to increasing levels of radiation and poses a potential infection risk to patients with frequent handling and access of the vial. New technologies for automated dosing and infusion delivery are available, however these incorporate both a multidose vial and a multi-patient infusion set. There is an absence of guidance for infection prevention (IP) units regarding the safety and acceptability of these devices. This paper describes the process of risk assessment and the mitigation measures for training, workflows, and documentation which led to the safe introduction of an automated PET infusion device in a large tertiary public healthcare facility.

Background Non-antibiotic interventions for urinary tract infection (UTI) prevention have been investigated as a strategy to reduce antibiotic prescribing for UTI and subsequent antibiotic resistance. Increased hydration is widely advocated for preventing UTI; however, evidence for its effectiveness is unknown. Aim To systematically review the published literature on the effectiveness of increased fluid intake as a preventive intervention for UTI in adults and children in any setting. Methods Five electronic databases were searched from inception to February 2019 to identify published randomized controlled trials (RCTs) and quasi-experimental studies evaluating the effectiveness of high (≥1.5 L/24 h) versus normal/low (

BACKGROUND:\ud Point prevalence studies identify that pneumonia is the most common healthcare associated infection. However, non-ventilator associated healthcare associated pneumonia (NV-HAP) is both underreported and understudied. Most research conducted to date, focuses on ventilator associated pneumonia. We conducted a systematic review, to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used.\ud \ud METHODS:\ud We performed a systematic search to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities. The electronic database Medline was searched, for peer-reviewed articles published between 1st January 1998 and 31st August 2018. An assessment of the study quality and risk of bias of included articles was conducted using the Newcastle-Ottawa Scale.\ud \ud RESULTS:\ud The literature search yielded 1551 articles, with 15 articles meeting the inclusion criteria. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9). Three studies evaluated a form of physical activity, such as passive movements, two studies used dysphagia screening and management; and another study evaluated prophylactic antibiotics. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials.\ud \ud CONCLUSION:\ud There was considerable heterogeneity in the included studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management.

Background: Children with comorbidities are at greater risk of severe influenza outcomes compared with healthy children. In Australia, influenza vaccination was funded for those with comorbidities from 2010 and all children aged

The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ten COVID-19 patients sampled longitudinally and ten age and gender matched healthy donors. We observed 55 miRNAs that were altered in COVID-19 patients during early-stage disease, with the inflammatory miR-31-5p the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-423-5p, miR-23a-3p and miR-195-5p) independently classified COVID-19 cases with an accuracy of 99.9%. In a ferret COVID-19 model, the three-miRNA signature again detected SARS-CoV-2 infection with 99.7% accuracy, and distinguished SARS-CoV-2 infection from influenza A (H1N1) infection and healthy controls with 95% accuracy. Distinct miRNA profiles were also observed in COVID-19 patients requiring oxygenation. This study demonstrates that SARS-CoV-2 infection induces a robust host miRNA response that could improve COVID-19 detection and patient management., Author summary While it is recognized that the host response to infection plays a critical role in determining the severity and outcome of COVID-19, the host microRNA (miRNA) response to SARS-CoV-2 infection is poorly defined. Here we have used next-generation sequencing and bioinformatics to profile circulating miRNAs in 10 COVID-19 patients that were sampled longitudinally over time. COVID-19 was associated with altered expression of 55 plasma miRNAs, with miR-776-3p and miR-1275 among the most strongly down-regulated, and miR-4742-3p, miR-31-5p and miR-3215-3p the most up-regulated. An artificial intelligence methodology was used to identify a miRNA signature, consisting of miR423-5p, miR-23a-3p, miR-195-5p, which could independently classify COVID-19 patients from healthy controls with 99.9% accuracy. When applied to the ferret model of COVID-19, the same signature classified COVID-19 cases with 99.8% accuracy and could distinguish between COVID-19 and influenza A(H1N1) infection with >95% accuracy. In summary this study profiles the host miRNA response to COVID-19 and suggests that the measurement of select host molecules may have potential to independently detect disease cases.

Background: Saudi Arabia being a major pilgrimage center with an annual turnover of millions of pilgrims from all over the world has a high risk for transmission of infections; Ebola virus disease (EVD) being one of them. Health care workers (HCWs) are particularly vulnerable to these infections. The objectives of this research were to assess the overall knowledge and infection control practices of HCWs about EVD, and to evaluate and compare the role of pre deployment Hajj training of HCWs assigned Hajj duties with those HCWs who did not receive this training. Methods: Through a comparative cross sectional study design a randomly selected representative sample of HCWs who performed Hajj duties in 2015 were compared with those who were not part of Hajj. Participants were taken from different Makkah and Jeddah region hospitals. A validated self-administered questionnaire was used to assess EVD awareness of 1216 HCWs. Chi square test was applied to check the association between the two groups using SPSS 22. Results: Overall, medical practitioners had a higher level of knowledge (76.5%) about EVD (in-terms of average correct answers) compared to nurses (59.6%) and other HCWs (56.7%). There was relatively poor knowledge about the EVD management, the Ebola cases fatality rate and the risk of the health care workers from this infectious disease. However, it was obvious that the HCWs who performed Hajj duties and underwent pre-deployment training had more knowledge and better practices about EVD compared to the Non Hajj HCWs and the difference was statistically significant (p

Background Recent criteria which can identify patients with Staphylococcus aureus bacteraemia (SAB) who are at very low risk of endocarditis raise the question of whether transoesophageal echocardiography (TOE) is appropriate for these patients. Aims To estimate the probability of occult endocarditis complicating SAB below which a TOE-guided treatment strategy no longer offers the best 180-day survival, and to examine the key uncertainties affecting this result. Sources Estimates of the parameters required to calculate the Pauker–Kassirer testing threshold were identified from studies published prior to 1 June 2017 using a composite search strategy that involved a systematic search for relevant controlled trials and guidelines, followed by a non-systematic iterative search of the observational literature. Content Estimates of the necessary parameters were generally consistent across the literature with the exception of the procedural mortality of TOE. In our base-case scenario (TOE mortality 0.1%), the testing threshold for TOE in apparently uncomplicated SAB was a 1.1% probability of occult endocarditis. Sensitivity analyses revealed that the procedural mortality of TOE was a key uncertainty affecting estimates of the testing threshold. Implications None of the available clinical tools can place patients with SAB below this probability of endocarditis with 95% confidence. Future work in this area should concentrate on improving the precision of these tools and on exploring the value of alternative echocardiography strategies. In addition, a better understanding of the harms of TOE is required to ensure that recommendations regarding the role of this investigation in the management of patients with SAB are appropriate.

Summary Background Healthcare-associated Staphylococcus aureus bloodstream infection (HA-SAB) causes preventable harm in hospitalized patients. Currently, there is no standardized method available to review HA-SAB events in order to identify and target preventable risks requiring action at an organizational level. Aim To develop a tool to classify SAB events, and the necessary response actions, according to the degree of preventability. Methods Following a literature review, a tool was developed. Consensus feedback and development of the tool was sought from experts (N = 11) in healthcare-associated infection surveillance using a Delphi technique. The completed tool was retrospectively applied to HA-SAB events (N = 43) that occurred at a large healthcare organization. Findings Survey completion rates were high (91–100%). Clinicians' poor adherence to infection prevention practices and lack of engagement with feedback processes was established as the key modifiable element. A second key theme was the need for structured and detailed response actions. This feedback was incorporated into the tool and refined until consensus on all elements was achieved. Pilot application of the tool found that 56% of HA-SAB events were highly or possibly preventable; modifiable factors for HA-SAB prevention were not present in the remainder of cases. Conclusion A prevention assessment and response tool was successfully developed via a consensus method to assist organizations in investigating and responding to individual cases of HA-SAB and identify future priority areas for SAB reduction strategies. Wider use of the tool with routine surveillance activities is required to evaluate impact upon infection prevention programmes and patient outcomes.

Objectives To assess the risks associated with relaxing coronavirus disease 2019 (COVID‐19)‐related physical distancing restrictions and lockdown policies during a period of low viral transmission. Design Network‐based viral transmission risks in households, schools, workplaces, and a variety of community spaces and activities were simulated in an agent‐based model, Covasim. Setting The model was calibrated for a baseline scenario reflecting the epidemiological and policy environment in Victoria during March–May 2020, a period of low community viral transmission. Intervention Policy changes for easing COVID‐19‐related restrictions from May 2020 were simulated in the context of interventions that included testing, contact tracing (including with a smartphone app), and quarantine. Main outcome measure Increase in detected COVID‐19 cases following relaxation of restrictions. Results Policy changes that facilitate contact of individuals with large numbers of unknown people (eg, opening bars, increased public transport use) were associated with the greatest risk of COVID‐19 case numbers increasing; changes leading to smaller, structured gatherings with known contacts (eg, small social gatherings, opening schools) were associated with lower risks. In our model, the rise in case numbers following some policy changes was notable only two months after their implementation. Conclusions Removing several COVID‐19‐related restrictions within a short period of time should be undertaken with care, as the consequences may not be apparent for more than two months. Our findings support continuation of work from home policies (to reduce public transport use) and strategies that mitigate the risk associated with re‐opening of social venues.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

Countries worldwide are experiencing a second wave of coronavirus disease 2019 (COVID-19), which is proving to be difficult to control. We describe the combination of physical distancing, mandatory mask wearing, movement restrictions, and enhanced test, trace, and isolation efforts that can be used to successfully suppress community transmission to zero.

To better understand primary and recall T cell responses during COVID-19, it is important to examine unmanipulated SARS-CoV-2-specific T cells. Using peptide-HLA tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed towards subdominant epitopes – B7/N257, A2/S269 and A24/S1208 – CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequency in pre-pandemic samples, and at increased frequency during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults and elderly individuals predominantly displayed a naïve phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαβ repertoires and promiscuous αβ-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαβ diversity within immunodominant B7/N105-specific CD8+ T cells, and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses., Graphical Abstract, Examining unmanipulated SARS-CoV-2-specific T cells is important for understanding primary and recall responses during COVID-19. Nguyen et al. analyze ex vivo CD8+ T cells specific for SARS-CoV-2 epitopes and find that immunodominant B7/N105-specific CD8+ T cells are present at high frequencies in blood samples from unexposed, acute COVID-19, and convalescence individuals, which is underpinned by diverse TCR repertoires.

Background It is commonly recommended that microbiological assessment should accompany the use of antibiotics prone to resistance. We sought to estimate the rate of microbiology testing and compare this to dispensing of the World Health Organization classified “watch” group antibiotics in primary care. Methods Data from a cohort of older adults (mean age 69 years) were linked to Australian national health insurance (Pharmaceutical Benefits Scheme & Medicare Benefits Schedule) records of community-based antibiotic dispensing and microbiology testing in 2015. Participant characteristics associated with greater watch group antibiotic dispensing and microbiology testing were estimated using adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) in multivariable zero-inflated negative binomial regression models. Results In 2015, among 244,299 participants, there were 63,306 watch group antibiotic prescriptions dispensed and 149,182 microbiology tests conducted; the incidence rate was 0.26 per person-year for watch group antibiotic dispensing and 0.62 for microbiology testing. Of those antibiotic prescriptions, only 19% were accompanied by microbiology testing within − 14 to + 7 days. After adjusting for socio-demographic factors and co-morbidities, individuals with chronic respiratory diseases were more likely to receive watch group antibiotics than those without, e.g. asthma (aIRR:1.59, 95%CI:1.52–1.66) and chronic obstructive pulmonary disease (COPD) (aIRR:2.71, 95%CI:2.48–2.95). However, the rate of microbiology testing was not comparably higher among them (with asthma aIRR:1.03, 95%CI:1.00–1.05; with COPD aIRR:1.00, 95%CI:0.94–1.06). Conclusions Priority antibiotics with high resistance risk are commonly dispensed among community-dwelling older adults. The discord between the rate of microbiology testing and antibiotic dispensing in adults with chronic respiratory diseases suggests the potential for excessive empirical prescribing.

Background Healthcare-associated infections (HAIs) and antimicrobial use (AMU) are important drivers of antimicrobial resistance, yet there is minimal data from the Pacific region. We sought to determine the point prevalence of HAIs and AMU at Fiji’s largest hospital, the Colonial War Memorial Hospital (CWMH) in Suva. A secondary aim was to evaluate the performance of European Centre for Diseases Prevention and Control (ECDC) HAI criteria in a resource-limited setting. Methods We conducted a point prevalence survey of HAIs and AMU at CWMH in October 2019. Survey methodology was adapted from the ECDC protocol. To evaluate the suitability of ECDC HAI criteria in our setting, we augmented the survey to identify patients with a clinician diagnosis of a HAI where diagnostic testing criteria were not met. We also assessed infection prevention and control (IPC) infrastructure on each ward. Results We surveyed 343 patients, with median (interquartile range) age 30 years (16–53), predominantly admitted under obstetrics/gynaecology (94, 27.4%) or paediatrics (83, 24.2%). Thirty patients had one or more HAIs, a point prevalence of 8.7% (95% CI 6.0% to 12.3%). The most common HAIs were surgical site infections (n = 13), skin and soft tissue infections (7) and neonatal clinical sepsis (6). Two additional patients were identified with physician-diagnosed HAIs that failed to meet ECDC criteria due to insufficient investigations. 206 (60.1%) patients were receiving at least one antimicrobial. Of the 325 antimicrobial prescriptions, the most common agents were ampicillin (58/325, 17.8%), cloxacillin (55/325, 16.9%) and metronidazole (53/325, 16.3%). Use of broad-spectrum agents such as piperacillin/tazobactam (n = 6) and meropenem (1) was low. The majority of prescriptions for surgical prophylaxis were for more than 1 day (45/76, 59.2%). Although the number of handwashing basins throughout the hospital exceeded World Health Organization recommendations, availability of alcohol-based handrub was limited and most concentrated within high-risk wards. Conclusions The prevalence of HAIs in Fiji was similar to neighbouring high-income countries, but may have been reduced by the high proportion of paediatric and obstetrics patients, or by lower rates of inpatient investigations. AMU was very high, with duration of surgical prophylaxis an important target for future antimicrobial stewardship initiatives.

Background Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). Methods A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program’s first 3 years (2016–2018). Results CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45–0.60 infections/100 000 population, P = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9–14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1–19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4–13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. Conclusions We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally., A statewide multimodal intervention for the control of carbapenemase-producing Enterobacterales was associated with a significant increase in case ascertainment, with no rise in clinical infections. Timely prospective epidemiological and genomic surveillance identified numerous small local transmission networks permitting rapid response.

Background The use of invasive devices increases the risk of healthcare associated infections (HAI). The recent national HAI point prevalence survey secondary outcomes aimed to estimate the prevalence of patients with an indwelling urinary catheter device and vascular access devices; and also identify prevalence of those managed under transmission based precautions (TBP); and those colonised or infected with a multi drug resistant organism (MDRO). Methods A point prevalence study was conducted in large acute care Australian public hospitals. All data were collected by two trained Research Assistants. Surveillance methodology was based on the European Centre for Disease Prevention and Control PPS Protocol. Data was also collected on prevalence of TBPs and MDROs. Results A total of 2767 acute adult inpatients were sampled across 19 hospitals. The prevalence of peripheral vascular, central vascular and urinary catheters devices was 55.2% (95%CI: 53.3%–57.1%), 14.8% (95%CI: 13.5%–16.1%) and 20.7% (95%CI: 19.2%–22.3%) respectively. Of the 2767 patients sampled 285 (10.3%, 95%CI: 9.2%–11.5%) were documented as either being infected or colonised with a MDRO, and 781 (11.8%) patients were being managed under the hospital TBP policy. Conclusion This is the first national study to describe the prevalence of devices, TBPs and MDROs in Australian healthcare settings. In an era where device use should be constantly reviewed to minimise risk of HAI, and the increasing challenges of managing patients with MDROs, this data can serve as a benchmark for future studies.

Acute lower respiratory infection (ALRI) is a major cause of hospitalization for Indigenous children in remote regions of Australia. The associated microbiology remains unclear. Our aim was to determine whether the microbes present in the nasopharynx before an ALRI were associated with its onset. A retrospective case-control/crossover study among Indigenous children aged up to 2 years. ALRI cases identified by medical note review were eligible where nasopharyngeal swabs were available: (1) 0–21 days before ALRI onset (case); (2) 90–180 days before ALRI onset (same child controls); and (3) from time and age-matched children without ALRI (different child controls). PCR assays determined the presence and/or load of selected respiratory pathogens. Among 104 children (182 recorded ALRI episodes), 120 case-same child control and 170 case-different child control swab pairs were identified. Human adenoviruses (HAdV) were more prevalent in cases compared to same child controls (18 vs 7%; OR = 3.08, 95% CI 1.22–7.76, p = 0.017), but this association was not significant in cases versus different child controls (15 vs 10%; OR = 1.93, 95% CI 0.97–3.87 (p = 0.063). No other microbes were more prevalent in cases compared to controls. Streptococcus pneumoniae (74%), Haemophilus influenzae (75%) and Moraxella catarrhalis (88%) were commonly identified across all swabs. In a pediatric population with a high detection rate of nasopharyngeal microbes, HAdV was the only pathogen detected in the period before illness presentation that was significantly associated with ALRI onset. Detection of other potential ALRI pathogens was similar between cases and controls. Electronic supplementary material The online version of this article (10.1007/s10096-018-3314-7) contains supplementary material, which is available to authorized users.

Background Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. Methods Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. Results Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. Conclusions This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications. Electronic supplementary material The online version of this article (10.1186/s12879-018-3011-2) contains supplementary material, which is available to authorized users.

Background Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia. Clinical guidelines recommend numerous measures to reduce the risk of OPSI, but awareness and adherence to preventative measures are generally poor. We aimed to determine whether a registry for asplenic/hyposplenic patients was associated with a reduction in the incidence of infection with encapsulated bacteria. Methods We performed a retrospective cohort study of asplenic/hyposplenic patients in the state of Victoria, Australia, who registered with Spleen Australia from 2003 through 2014. Spleen Australia provides education, clinical guidance, and annual vaccination reminders to registrants and their healthcare providers. We compared the incidence of infection with Streptococcus pneumoniae, Haemophilus influenzae type B (Hib), and Neisseria meningitidis before and after registration. Registry data were linked with Victorian notifiable disease data on invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD), and Hib between 2000 and 2014. Results Twenty-seven cases of IPD and 1 of IMD occurred among 3221 registrants. No cases of Hib were reported. The rate of IPD/IMD was 150 per 100000 patient-years prior to registration and 36 per 100000 patient-years after registration; registration was associated with a 69% reduction in the risk of infection (incidence rate ratio, 0.31; 95% confidence interval, 0.12 to 0.83; P = .019). Based on the absolute reduction in incidence, we estimate that Spleen Australia prevents 5-6 invasive infections with encapsulated organisms annually among registrants. Conclusions Systematic, long-term approaches to post-splenectomy care can significantly reduce the risk of infection with encapsulated organisms among individuals with asplenia/hyposplenism.

Gram-negative bacteria that are resistant to antimicrobials, including carbapenems, have emerged as a significant global public health threat. Multidrug-resistant gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae (CPE), place patients at risk of potentially untreatable infection. Australia has not reported a large number of CPE cases compared to Europe, North America, and the Middle East, creating an opportunity to prevent CPE from becoming established in Australia. An outbreak of Klebsiella pneumoniae carbapenemase in 2014 demonstrated there was variable testing, reporting, response to and communication of CPE. In response, the Australian Commission on Safety and Quality in Health Care formed a taskforce to assist health facilities to respond to the threat of CPE. Recommendations for state and territory health departments include coordinating a risk assessment, undertaking epidemiological and microbiological investigations, determining the requirement for control measures, and coordinating risk-communication activities. The response should take advice from experts in infectious diseases, microbiology, public health, infection prevention and control and epidemiologists. The guide aims to: •Alert healthcare professionals, health departments and hospital executives to the emerging threat of CPE in Australia •Recommend strategies to prevent, detect and contain CPE •Provide information and resources for hospital executives, healthcare professionals and consumers •Recommend laboratory screening and confirmation methods. The recommendations with rationale and commentary have been structured into sections depending on the burden of CPE in the health facility. The sections include: planning, preparing and prevention; CPE screening and surveillance; strategies to reduce CPE transmission; outbreak management; laboratory screening and confirmation methods.

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study.Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature.We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%).The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

Background There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. Methods We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Results Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Conclusions Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

Background A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications. Methods In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining. Results At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α-positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively). Conclusions Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes.

Background. Annual influenza vaccine is recommended for those at greatest risk of severe influenza infection. Recent reports of a negative impact of serial influenza vaccination on vaccine effectiveness (VE) raises concerns about the recommendation for annual influenza vaccines, particularly in persons at greatest risk. Methods. The Influenza Complications Alert Network (FluCAN) is an Australian hospital-based sentinel surveillance program. In this observational study, cases were defined as subjects aged >9 years admitted with influenza confirmed by polymerase chain reaction. Controls were subjects with acute respiratory illness testing negative for influenza. Propensity scores were used to adjust for the likelihood of being vaccinated. VE was calculated as 1 - adjusted odds ratio of vaccination in cases compared with test-negative controls. Results. Over 2010-2015, 6223 cases and 6505 controls were hospitalized with confirmed influenza and influenza test-negative acute respiratory illness, respectively. Following stratification by quintile of propensity score, site, and year, VE was estimated to be 43% (95% confidence interval [CI], 37%-49%) overall. VE was estimated to be 51% (95% CI, 45%-57%) in those vaccinated in both the current and previous season, compared with 33% (95% CI, 17%-47%) vaccinated in the current season only and 35% (95% CI, 21%-46%) in the previous season only. Similar results were observed for influenza A/H1N1, influenza A/H3N2, and influenza B strains. Conclusions. Vaccination in both the current and previous seasons was associated with a higher VE against hospitalization with influenza than vaccination in either single season. These findings reinforce current recommendations for annual influenza vaccination, particularly those at greatest risk of influenza disease.

• Crusted scabies is a highly infectious hyperkeratotic dermatosis caused by an ectoparasite S. scabiei variety hominis .

SUMMARYAustralia's National Immunisation Program (NIP) provides free influenza vaccination for children at high risk of severe influenza; a pilot-funded programme for vaccine in all children aged 6 months to

Summary In February, 2016, WHO released a report for the development of national action plans to address the threat of antibiotic resistance, the catastrophic consequences of inaction, and the need for antibiotic stewardship. Antibiotic stewardship combined with infection prevention comprises a collaborative, multidisciplinary approach to optimise use of antibiotics. Efforts to mitigate overuse will be unsustainable without learning and coordinating activities globally. In this Personal View, we provide examples of international collaborations to address optimal prescribing, focusing on five countries that have developed different approaches to antibiotic stewardship—the USA, South Africa, Colombia, Australia, and the UK. Although each country's approach differed, when nurtured, individual efforts can positively affect local and national antimicrobial stewardship programmes. Government advocacy, national guidelines, collaborative research, online training programmes, mentoring programmes, and social media in stewardship all played a role. Personal relationships and willingness to learn from each other's successes and failures continues to foster collaboration. We recommend that antibiotic stewardship models need to evolve from infection specialist-based teams to develop and use cadres of health-care professionals, including pharmacists, nurses, and community health workers, to meet the needs of the global population. We also recommend that all health-care providers who prescribe antibiotics take ownership and understand the societal burden of suboptimal antibiotic use, providing examples of how countries can learn, act globally, and share best antibiotic stewardship practices.

Summary Background Australia is a high-income country with a well established and largely publicly funded health-care system. However, some populations within Australia have shorter life expectancy and worse health outcomes than others. We explored geographical variations and sociodemographic inequities in infectious disease notifications in Australia. Methods In this retrospective study, we analysed National Notifiable Diseases Surveillance System (NNDSS) notifications from 1991–2011 (n=2·4 million). We assessed the effect of socioeconomic disadvantage and remoteness of residence on national notification incidence. We calculated Gini coefficients, adjusted relative risks (aRRs), population attributable fractions (PAFs), and attributable notifications. We reported aRRs for Indigenous status in three jurisdictions with more than 75% completeness of Indigenous status reporting from the Northern Territory, South Australia, and Western Australia. Findings Of the eight most commonly notified diseases from Jan 1, 1991, to Dec 31, 2011, gonococcal infection was the most geographically unequal and campylobacteriosis was the most evenly distributed across the country. Overall, notification incidence was higher in remote and very remote areas than in major cities (aRR 3·37), and higher in the most socioeconomically disadvantaged quintiles compared with less disadvantaged quintiles (aRR 1·15). The PAF for socioeconomic disadvantage was high for blood-borne viral hepatitis but decreased in other disease groups. In 2011, sexually transmitted infections had 11 093 notifications attributed to remoteness and 5597 notifications attributable to socioeconomic disadvantage. Notification incidence was higher in Indigenous than in non-Indigenous Australians (aRR 5·3). Interpretation All diseases had differing geographical concentration and sociodemographic risk. Overall, sociodemographic inequities in infectious disease notifications have decreased, but remain unacceptably high. National communicable disease control is complex, requiring both targeted and population-wide interventions. Funding None.

Mycobacterium chimaera infection in patients who have had cardiac bypass surgery has recently been associated with contamination of water in heater cooler units. Those responsible for infection prevention and control programs face the challenge of responding to this rare but potentially life-threatening and avoidable healthcare-associated infection. Infection control professionals need to be aware of this issue and take an active role in formulating hospital responses. Policies should be rational and appropriate to the level of risk, should minimise service disruption and costs, and recognise that evidence about risk mitigation measures is still emerging. This paper provides background information to the topic and proposes a risk management based approach to heater cooler units in hospitals that perform cardiac bypass surgery, so that infection control professionals can develop a local, tailored response.

BACKGROUND: The effectiveness of influenza vaccine during 2015–2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)–predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). METHODS: We estimated the effectiveness of influenza vaccine against polymerase chain reaction–confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010–2011 season through the 2015–2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918–2015. VE was calculated as 100 × [1 – adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus–positive versus influenza test–negative patients. RESULTS: A total of 2115 A(H1N1)pdm09 virus–positive and 14 696 influenza virus–negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%–66%) against A(H1N1)pdm09-associated illness during the 2010–2011 through 2013–2014 seasons, compared with 47% (95% CI, 36%–56%) during 2015–2016. During 2015–2016, A(H1N1)pdm09-specific VE was 22% (95% CI, −7%–43%) among adults born during 1958–1979 versus 61% (95% CI, 54%–66%) for all other birth cohorts combined. CONCLUSION: Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015–2016 and early exposure to specific influenza A(H1N1) viruses.

Objectives The epidemiology, clinical characteristics and outcomes of antimicrobial-associated anaphylaxis remain ill-defined. We sought to examine antimicrobial anaphylaxis with regard to: (i) the frequency of implicated antimicrobials; (ii) attributable mortality; and (iii) referral for definitive allergy assessment. Methods This was conducted through a national retrospective multicentre cohort study at five Australian tertiary hospitals (January 2010 to December 2015). Cases of antimicrobial anaphylaxis were identified from ICD-10 coding and adverse drug reaction committee databases. Results There were 293 participants meeting the case definition of antimicrobial anaphylaxis and 310 antimicrobial anaphylaxis episodes. Of 336 implicated antimicrobials, aminopenicillins (62/336, 18.5%) and aminocephalosporins (57/336, 17%) were implicated most frequently. ICU admission occurred in 43/310 (13.9%) episodes; however, attributable mortality was low (3/310, 1%). The rate of anaphylaxis to IV antibiotics was 3.5 (95% CI = 2.9–4.3) per 100 000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI = 2.1–3.3) per 100 000 occupied bed-days. We observed overall low rates of hospital discharge documentation (222/310, 71.6%) and follow-up by specialist allergy services (73/310, 23.5%), which may compromise medication safety and antimicrobial prescribing in future. Conclusions This study demonstrated that a high proportion of severe immediate hypersensitivity reactions presenting or acquired in Australian hospitals are secondary to aminopenicillins and aminocephalosporins. Overall rates of hospital-acquired anaphylaxis, predominantly secondary to cephalosporins, are low, and also associated with low inpatient mortality.