In this study, we aimed to estimate the burden of invasive Group A Streptococcus (iGAS) infection in Australia and describe the risk factors and outcomes across regions and populations. Studies published in six databases until October 2025 were included. The first study included in the systematic review was published in 1996. The review was registered in PROSPERO (CRD42023493112). The quality was assessed using The Joanna Briggs Institution checklist for prevalence studies. Common presentations, outcomes, risk factors, seasonality and emm types were systematically reviewed. A meta-analysis was conducted to estimate pooled incidence. Forty-one articles were included in the systematic review and 10 were included in the meta-analysis. The pooled incidence of iGAS was 7.97 per 100,000 person-years (95

This review discusses the trends of bacteraemia and their outcomes in tropical regions of Australia. Bacteraemia can frequently lead to severe sepsis and potentially life-threatening consequences. Epidemiology of bacteraemia is ever evolving. This review outlines the current patterns of bacteraemia in tropical regions of Australia, focusing on their outcomes and associated risk factors. The most frequently reported causes of bacteraemia were Staphylococcus aureus and Escherichia coli. There has been an increase in published incidence of Group A Streptococcus, methicillin-resistant Staphylococcus aureus and Burkholderia pseudomallei bacteraemia cases, while Streptococcus pneumoniae bacteraemia exhibited a declining trend. Factors specific to tropical environments and the higher representation of Indigenous populations in these areas were identified as contributing to the elevated incidence rates. Bacteraemia was found to be an increasing healthcare burden to the Australian tropical regions. Ideally, linkage of existing data from healthcare settings could be utilised to obtain more accurate, comprehensive and up to date information of trends and patterns of bacteraemia.

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Reference genes are frequently used for the normalization of quantitative reverse transcriptase PCR (qRTPCR) data in gene expression studies. Staphylococcus aureus is one of the most common causes of biofilm-related infections. Savirin and ticagrelor show in vitro as well as in vivo antibiofilm activity against S. aureus. The main aim of this study was to identify the most stably expressed reference genes to study the effect of these molecules on genes in a strong biofilm producing S. aureus isolate isolated from biofilm-related infection. Quantitative real-time PCR was performed by using relative quantification method. Four different algorithms, delta Ct, normfinder, bestkeeper, and genorm, followed by a comprehensive analysis was used to identify the most stable reference genes from a list of sixteen different candidate reference genes. All four algorithms reported different results, with some comparable findings among some methods. In the comprehensive analysis of the results of all the algorithms used, the most stable reference genes found were spa, rpoD, and pyk for savirin treatment experiment and gapdH, gyrA, and gmk for ticagrelor treatment experiment. The optimal number of reference genes required was two for both the experimental conditions. Despite having some drawbacks, each algorithm can reliably determine an appropriate reference gene independently. However, based on consensus ranking and the required optimal number of reference genes reported, spa and rpoD were the most appropriate reference genes for savirin treatment experiment, and gapdH and gyrA were most appropriate for ticagrelor treatment experiment. This study provides baseline data on reference genes to study the effect of savirin or ticagrelor treatment on the expression of potential reference genes in S. aureus. We recommend prior re-validation of reference genes on a case-by-case basis before they can be used.

BACKGROUND:Bacterial biofilm is a key component in the pathogenesis of prosthetic joint infection (PJI). Synovial fluid has been shown to have inhibitory activity against planktonic bacteria. However, the contribution of synovial fluid in prevention of Staphylococcus aureus (including MRSA) planktonic and biofilm forms is unknown.OBJECTIVES:To test the antibacterial and antibiofilm activities of synovial fluid, including that containing cefazolin, against MSSA and MRSA.MATERIALS AND METHODS:We determined the antiplanktonic and antibiofilm activities of synovial fluid collected from patients given preoperative cefazolin while undergoing elective arthroplasty surgery. MICs of cefazolin were determined for planktonic and biofilm cultures of biofilm-forming strains of MSSA and MRSA.RESULTS:Synovial fluid inhibited planktonic and biofilm cultures of MSSA and MRSA. Cefazolin-containing synovial fluid had greater antibacterial and antibiofilm activities than the same cefazolin concentration in glucose LB (GLB) broth. MSSA and MRSA MICs of cefazolin suspended in synovial fluid were 0.7 mg/L. The MICs of cefazolin diluted in GLB broth were higher, measuring 1.4 mg/L for MSSA and 23 mg/L for MRSA.CONCLUSIONS:Synovial fluid containing cefazolin inhibited biofilm- and planktonic-state MRSA cultures. This may explain the apparent effect of cefazolin in the prevention of MRSA PJI.

Background: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI. Materials and methods: The in-vitro antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against S. aureus were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven. Results: Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues. Conclusion: Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study gives baseline data for using savirin for the prevention as well as treatment of S. aureus PJI in future animal studies.

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I 2 = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.

Background: Prosthetic joint infection (PJI), frequently caused by Staphylococcus aureus, leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of S. aureus that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment. Surgical and antibiotic therapy could be combined with non-antibacterial adjuvants to improve overall treatment success. Ticagrelor, a P2Y12 receptor inhibitor antiplatelet drug, is known to have anti-staphylococcal antibacterial and antibiofilm activity. However, the molecular mechanism for ticagrelor’s antibiofilm activity and its efficacy in the treatment of S. aureus PJI are unknown.Methods: To study the in vitro antibacterial and antibiofilm activity of ticagrelor, broth microdilution and crystal violet staining method were used. Ticagrelor’s effect on the expression of S. aureus biofilm genes (icaA, icaD, ebps, fib, eno, and agr) was studied using the relative quantification method. To test ticagrelor’s in vivo efficacy to treat S. aureus PJI, mice were randomized into five groups (n = 8/group): infected femoral implants treated with ticagrelor alone; infected implants treated with cefazolin alone; infected implants treated with ticagrelor and cefazolin; infected implants treated with phosphate buffer solution (PBS)-positive controls, and sterile implants-negative controls. Ticagrelor was administered orally from day 4 to day 7 post-surgery, while cefazolin was injected intravenously on day 7.Results: Ticagrelor, alone and with selected antibiotics, showed in vitro antibacterial and antibiofilm activity against S. aureus. Strain-specific downregulation of biofilm-related genes, fib, icaD, ebps, and eno, was shown. In an animal model of biofilm-related S. aureus PJI, ticagrelor alone and combined with cefazolin significantly reduced bacterial concentrations on the implants compared with the positive control group. Ticagrelor significantly reduced bacterial dissemination to periprosthetic tissue compared with the positive controls.Conclusion: Ticagrelor adjuvant therapy reduced S. aureus PJI in an animal model. However, this study is very preliminary to make a conclusion on the clinical implication of the findings. Based on the current results, more studies are recommended to better understand its implication.

Background: In this study, we aimed to assess the risk factors associated with mortality due to an infectious disease over the short-, medium-, and long-term based on a data-linkage study for patients discharged from an infectious disease unit in North Queensland, Australia, between 2006 and 2011. Methods: Age-sex standardised mortality rates (SMR) for different subgroups were estimated, and the Kaplan-Meier method was used to estimate and compare the survival experience among different groups. Results: Overall, the mortality rate in the hospital cohort was higher than expected in comparison with the Queensland population (SMR: 15.3, 95%CI: 14.9–15.6). The long-term mortality risks were significantly higher for severe infectious diseases than non-infectious diseases for male sex, Indigenous, residential aged care and elderly individuals. Conclusion: In general, male sex, Indigenous status, age and comorbidity were associated with an increased hazard for all-cause deaths.

Background: The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first detected in the city of Wuhan, China has now spread to every inhabitable continent, but now the attention has shifted from China to other epicentres. This study explored early assessment of the influence of spatial and travel patterns from Italy on the further spread of SARS-CoV-2 worldwide. Methods: Using data on the number of confirmed cases of COVID-19 and air travel data between countries, we applied a stochastic meta-population model to estimate the global spread of COVID-19. Pearson's correlation, semi-variogram, and Moran's Index were used to examine the association and spatial autocorrelation between the number of COVID-19 cases and travel influx (and arrival time) from the source country. Results: We found significant negative association between disease arrival time and number of cases imported from Italy (r = -0.43, p = 0.004) and significant positive association between the number of COVID-19 cases and daily travel influx from Italy (r = 0.39, p = 0.011). Using bivariate Moran's Index analysis, we found evidence of spatial interaction between COVID-19 cases and travel influx (Moran's I = 0.340). Asia-Pacific region is at higher/extreme risk of disease importation from the Chinese epicentre, whereas the rest of Europe, South-America and Africa are more at risk from the Italian epicentre. Conclusion: We showed that as the epicentre changes, the dynamics of SARS-CoV-2 spread change to reflect spatial proximities.

OBJECTIVE:To investigate the admission characteristics and hospital outcomes for patients admitted with lower respiratory tract infections (LRTI) in Northern Queensland.METHODS:We perform a retrospective analysis of the data covering an 11-year period, 2006-2016. Length of hospital stay (LOS) is modelled by negative binomial regression and heterogeneous effects are checked using interaction terms.RESULTS:A total of 11,726 patients were admitted due to LRTI; 2,430 (20.9%) were of Indigenous descent. We found higher hospitalisations due to LRTI for Indigenous than non-Indigenous patients, with a disproportionate increase in hospitalisations occurring during winter. The LOS for Indigenous patients was higher by 2.5 days [95%CI: -0.15; 5.05] than for non-Indigenous patients. The average marginal effect of 17.5 [95%CI: 15.3; 29.7] implies that the LOS for a patient, who was admitted to ICU, was higher by 17.5 days.CONCLUSIONS:We highlighted the increased burden of LRTIs experienced by Indigenous populations, with this information potentially being useful for enhancing community-level policy making. Implications for public health: Future guidelines can use these results to make recommendations for preventative measures in Indigenous communities. Improvements in engagement and partnership with Indigenous communities and consumers can help increase healthcare uptake and reduce the burden of respiratory diseases.

Hearing loss is an unusual presenting feature of Cryptococcus gattii meningoencephalitis. Two cases of HIV-negative patients who presented with hearing loss are discussed and a literature review of published cases was conducted. Possible mechanisms for hearing loss with C. gattii infection are explored. This case series aims to raise awareness among clinicians that hearing loss can be a concerning feature in patients with persistent headache necessitating further investigation.

Staphylococcus aureus frequently causes community- and hospital-acquired infections. S. aureus attachment followed by biofilm formation on tissues and medical devices plays a significant role in the establishment of chronic infections. Staphylococcal biofilms encase bacteria in a matrix and protect the cells from antimicrobials and the immune system, resulting in infections that are highly resistant to treatment. The biology of biofilms is complex and varies between organisms. In this review, we focus our discussion on S. aureus biofilms and describe the stages of their formation. We particularly emphasize genetic and biochemical processes that may be vulnerable to novel treatment approaches. Against this background, we discuss treatment strategies that have been successful in animal models of S. aureus biofilm-related infection and consider their possible use for the prevention and eradication of biofilm-related S. aureus prosthetic joint infection.

Acute respiratory infections appear to precipitate vascular events. Acute myocardial infarction (AMI) and stroke are the leading cause of death and disability globally. This study was based on a cohort of patients admitted to Townsville University Hospital between January 2006 and December 2016. Using a self-controlled case series design, we investigated the risk of AMI or ischaemic stroke after an episode of pneumonia. We defined the ‘risk interval’ as the first 14 days after hospitalisation for pneumonia and the ‘control interval’ as one year before and one year after the risk interval. Among a population (N = 4557) with a median age of over 70, a total of 128 AMI and 27 stroke cases were identified within 1 year of an episode of pneumonia in this study. Ten and two admissions occurred during the risk interval, while 118 and 25 admissions occurred during the control period. The relative incidence ratios (RIR) of AMI increased after an episode of pneumonia (RIR=4.85, 95% confidence interval (CI) 2.44–9.67). The risk for stroke after the exposure period of 14 days was 4.94 (95% CI 1.12–21.78) considering only the first stroke incidence. The RIR results for AMI and stroke were not altered by adjusting for age, sex or Indigenous status. The risk of AMI and stroke were significantly higher two weeks after an episode of pneumonia.

The aim of this study was to systematically review the non-endocarditis manifestations of chronic Q fever and understand the significance of non-specific symptoms like pain and fatigue in chronic endovascular, osteomyelitis and abscess due to chronic Q fever. We performed a systematic review using Pub Med (the National Library of Medicine (NLM)) and Scopus databases. All studies in English on chronic Q fever that listed clinical manifestations other than infective endocarditis (IE) and chronic fatigue syndrome (CFS). Meta-analysis was carried out to investigate the effects of patient’s health outcomes (pain, fatigue, the need for surgery and mortality) on vascular infections, osteomyelitis and abscess. Among cases not presenting as IE or CFS, vascular infections and osteomyelitis were the most common chronic Q fever disease manifestations. There were distinct regional patterns of disease. Compared with infective endocarditis, these are significantly associated with increased risk of pain: osteomyelitis (relative risk (RR) = 4.13, 95% confidence interval (CI) 3.36–5.07), abscess (RR = 3.59, 95% CI 3.28–3.93) and vascular infection (RR = 2.46, 95% CI 1.99–3.03). The strongest significant association was observed between osteomyelitis and pain. There was no significant association between fatigue and these manifestations. Clinicians have to be aware of uncommon manifestations of chronic Q fever as they present with non-specific symptoms and are significantly associated with increased risk of morbidity and mortality. The findings emphasise the need to investigate patients with positive chronic Q fever serology presenting with acute or chronic pain for possible underlying complications.

COVID-19 is not only a global pandemic and public health crisis; it has also severely affected the global economy and financial markets. Significant reductions in income, a rise in unemployment, and disruptions in the transportation, service, and manufacturing industries are among the consequences of the disease mitigation measures that have been implemented in many countries. It has become clear that most governments in the world underestimated the risks of rapid COVID-19 spread and were mostly reactive in their crisis response. As disease outbreaks are not likely to disappear in the near future, proactive international actions are required to not only save lives but also protect economic prosperity.

PURPOSE:To design a linked hospital database using administrative and clinical information to describe associations that predict infectious diseases outcomes, including long-term mortality. PARTICIPANTS:A retrospective cohort of Townsville Hospital inpatients discharged with an International Classification of Diseases and Related Health Problems 10th Revision Australian Modification code for an infectious disease between 1 January 2006 and 31 December 2016 was assembled. This used linked anonymised data from: hospital administrative sources, diagnostic pathology, pharmacy dispensing, public health and the National Death Registry. A Created Study ID was used as the central identifier to provide associations between the cohort patients and the subsets of granular data which were processed into a relational database. A web-based interface was constructed to allow data extraction and evaluation to be performed using editable Structured Query Language. FINDINGS TO DATE:The database has linked information on 41 367 patients with 378 487 admissions and 1 869 239 diagnostic/procedure codes. Scripts used to create the database contents generated over 24 000 000 database rows from the supplied data. Nearly 15% of the cohort was identified as Aboriginal or Torres Strait Islanders. Invasive staphylococcal, pneumococcal and Group A streptococcal infections and influenza were common in this cohort. The most common comorbidities were smoking (43.95%), diabetes (24.73%), chronic renal disease (17.93%), cancer (16.45%) and chronic pulmonary disease (12.42%). Mortality over the 11-year period was 20%. FUTURE PLANS:This complex relational database reutilising hospital information describes a cohort from a single tropical Australian hospital of inpatients with infectious diseases. In future analyses, we plan to explore analyses of risks, clinical outcomes, healthcare costs and antimicrobial side effects in site and organism specific infections.

BACKGROUND:Sepsis is a serious global health issue and a major cause of death and disability. The availability of a simple, community-based preventive strategy could substantially reduce the burden of sepsis. We aimed to establish whether low-dose aspirin reduced deaths or hospital admissions associated with sepsis in older people. METHODS:ANTISEPSIS was a substudy of ASPREE (a randomised controlled primary prevention trial of low-dose aspirin [100 mg per day] compared with placebo in community dwelling older adults conducted in Australia and the USA), with the Australian cohort included in the ANTISEPSIS substudy. Inclusion criteria were participants aged at least 70 years who did not have major illnesses. Participants were block randomised (1:1) via a centralised web portal and stratified by general practice and age. Participants, investigators, and staff were masked to the intervention. Teams of clinical specialist investigators assessed potential sepsis events to establish if they satisfied the primary endpoint of death associated with sepsis. The analyses were by intention-to-treat with univariate survival analysis methods, the log-rank test, and Cox proportional hazards regression. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000349741. RESULTS:Between March 10, 2010, and Dec 24, 2014, of 20 288 individuals assessed for eligibility, 16 703 participants aged 70 years and older at trial entry were enrolled and followed up for a median of 4·6 years (IQR 3·6-5·6). 8322 (49·8%) participants were assigned to receive aspirin and 8381 (50·2%) to placebo. 203 deaths were considered to be associated with sepsis. Univariate analysis showed similar rates of death associated with sepsis in the two study groups (hazard ratio for aspirin vs placebo 1·08, 95% CI 0·82-1·43; p=0·57). Adverse events were previously reported in the ASPREE trial. INTERPRETATION:Daily low-dose aspirin treatment did not reduce deaths associated with sepsis in community dwelling older adults. Our findings do not support the use of aspirin as a primary prevention strategy to reduce the burden of sepsis in this population. FUNDING:National Health and Medical Research Council of Australia, National Institutes of Health, Monash University.