Invasive group A streptococcal infections in Australian adults – a descriptive cohort and cost burden study

Invasive group A streptococcal infections in Australian adults – a descriptive cohort and cost burden study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Invasive group A streptococcal infections in Australian adults – a descriptive cohort and cost burden study Jessie J Goldsmith, Sara L Whittaker, Eddie Chan, Jake A Lacey, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5847008/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Objectives: To describe the epidemiology, clinical course, genomics, and cost burden of hospital care of invasive group A streptococcal (iGAS) amongst adults (≥18 years) treated at the Royal Melbourne Hospital (RMH) during 2018-2023 and extrapolate findings to estimate the annual healthcare cost burden of treating adult iGAS cases in Australia. Methods: Retrospective cohort study and economic evaluation, including a single hospital cost burden analysis followed by a national cost extrapolation. Results: There were 79 eligible iGAS cases between 2018-2023. Seven cases were fatal (case fatality rate: 9%, 95% CI: 4%–18%), one third (29, 35%) were admitted to intensive care and one third (27; 38%) of non-fatal cases were discharged with an impairment. The average iGAS disease-related healthcare cost was $63,662 (SD $84,743) per person, with a combined healthcare utilisation cost for the cohort of $5,029,305. Most costs (80%) were incurred during the index admission. In 2023, the estimated national healthcare cost burden for adults with iGAS was $117.5 million. Conclusions: iGAS among adults in Australia generates a significant health and financial burden. Our findings highlight the importance of investment in research to prevent iGAS and identify the optimal treatment for this severe infection. invasive group A streptococcal disease cost burden study Figures Figure 1 Figure 2 Background Invasive group A Streptococcus (iGAS) is a rare, severe and rapidly progressive disease caused by Streptococcus pyogenes , 1 with a variety of clinical syndromes including sepsis, necrotising fasciitis, and streptococcal toxic shock syndrome (STSS). Even with prompt antibiotics and supportive treatments, iGAS case-fatality-rates (CFR) in well-resourced settings range from 8%–16% 1 and a significant proportion of survivors are discharged from hospital with a physical impairment. 2,3 The healthcare costs associated with treating paediatric iGAS in Australia was estimated to be $6.2 million in 2019. 4 However, the healthcare cost of iGAS in adults in Australia is not known. Prior to the emergence of COVID-19, the incidence of iGAS was rising in many high-income countries, including the USA, New Zealand, Canada, and Australia. 2,5–7 Following the easing of COVID-19 restrictions there was a global surge in iGAS, with disease incidence surpassing the long-term trend. 8,9 The burden of iGAS is inequitable. In Australia and other regions, First Nations people and people who inject drugs (PWID) are four- to eight-fold 5,7,10 and three to 14-fold, 11,12 respectively, more likely to be diagnosed with iGAS than other populations. There is evidence of substantial variation in clinical management of iGAS, both across jurisdictions and between individual clinicians, despite penicillin being the recommended targeted treatment 1 . A Finnish study of GAS bacteraemia cases found for cases not requiring admission to an intensive care unit (ICU), penicillin use was higher for cases who received an infectious diseases clinician consultation compared to those who did not (59% vs. 21%). 13 There is also considerable variation in the use of adjunctive therapies such as clindamycin, linezolid and intravenous immunoglobulin (IVIg), 14–16 for which the evidence supporting their use is equivocal. 17 At present there is limited available evidence regarding clinical management of iGAS in Australia. The growing incidence of iGAS and the inequitable burden on First Nations people are reasons to prioritise investment in research to improve prevention and management of iGAS. Quantifying the hospital cost burden for adult iGAS cases and describing the variability of treatment approach in Australia provides evidence to support this argument. Here we describe the epidemiology, clinical course, genomics, and healthcare cost burden of iGAS amongst adult cases presenting to the Royal Melbourne Hospital (RMH) during 2018-2023 and extrapolate the costs to determine the national healthcare cost burden for adults with iGAS in Australia in 2023. Method The RMH is an adult quaternary hospital in Victoria, Australia, with a 42-bed intensive care unit (ICU). iGAS cases aged ≥18 years and diagnosed from 01/01/2018–31/12/2023, where S. pyogenes was cultured from a normally sterile site, were included. This study was approved by the RMH Human Research Ethics Committee (HREC/49200/MH-2018). Data collection Patient data were extracted from the electronic medical records of their index hospital admission for iGAS by infectious diseases physicians to a study REDCap (Research Electronic Data Capture) database hosted at The University of Melbourne. 18,19 We recorded demographics, comorbidities (including injecting drug use), iGAS manifestations and outcomes, length-of-stay, ICU admission, surgical interventions, and use of antibiotics and IVIg. Outcomes among survivors were defined at the time of hospital discharge as disability (permanent physical impairment), deficit (physical impairment anticipated to improve post-discharge), or no disability/deficit. Whole genome sequencing (WGS) of a single S. pyogenes isolate from included iGAS cases was undertaken prospectively by the Microbiological Diagnostic Unit Public Health Laboratory according to accredited laboratory workflows using the Illumina NextSeq platform. For further information refer to the paper by Morris et.al. 20 Individual patient cost-of-care data for included iGAS cases were provided by the RMH Health Intelligence Unit. Clinical cost data included health care costs and utilization for the index iGAS admission at RMH (all included cases), and other costs of care delivered by RMH during the six-month period following the date of the index hospital admission for iGAS. Contacts comprised the index admission to RMH as well as all RMH services in the 6-months following the index admission, including investigations (laboratory tests, imaging), allied health visits, prescribed medications, hospital-in-the-home, re-admissions, and outpatient appointments. Cost data for each contact with the RMH were presented as a total, and by resource categories (‘cost buckets’) including allied health, emergency department, ICU, imaging, medical, nursing, pathology, pharmacy and other. Other data included length-of-stay (in days) for the index admission and all re-admissions within six months. Data analysis Cases were classified by whether they were admitted to the ICU and by the following iGAS manifestations: bacteraemia with or without focus, osteomyelitis or septic arthritis, STSS, pneumonia or empyema, necrotizing soft tissue infection, non-necrotizing soft tissue infection, and other. STSS was defined as an iGAS case with hypotension (systolic blood pressure <90 mmHg) and multi-organ involvement, according to the CDC’s STSS 2010 Case Definition 21 . Cases could have more than one manifestation. Demographic and clinical features and GAS emm -types were described for iGAS cases and compared using the Wilcoxon rank sum test or Pearson chi-squared test. Antibiotics were classified as empiric (broad spectrum antibiotics not specifically directed towards S. pyogenes , including carbapenems, fourth generation cephalosporins, extended-spectrum penicillins, glycopeptides), directed (targeted to S. pyogenes , including narrow spectrum penicillins, 2 nd or 3 rd generation cephalosporins) or adjunctive (used to reduce toxin production, including clindamycin and linezolid), and their use was described over the first 10 days after hospital admission. For emm -types with at least five cases, odds ratios (OR) by emm -type were calculated according to need for ICU admission. The Bonferroni correction method was used to adjust p-values (calculated using Fisher’s exact test) and confidence intervals to account for multiple hypothesis testing. Cost burden RMH cost data were matched to clinical case data. The cost analysis presents the unit definition, unit cost, unit quantity and total cost for each resource (i.e. ‘cost buckets’), presented as a mean and standard deviation (SD). Each of the units were added together to present a per person cost for the index admission and the subsequent care in the 6 months post-discharge. Where cost data were incomplete, average costs and the case’s reported length-of-stay and utilisation data were used to model the missing data. Individual case-level cost and utilisation data were analysed from a health system perspective. A sub-group analysis was completed excluding cases that died during the index admission. Opportunity costs were not included in this cost analysis. All costs were converted via Consumer Price Index (CPI) 22 to the 2023 calendar year and presented as $AUD. National cost burden extrapolation The national cost burden for all adult (≥18 years) iGAS hospitalisations was estimated using extrapolation. The cost per case by gender and age produced in the cost analysis was multiplied by the incidence by age and gender for each Australian jurisdiction. For this extrapolation, incidence was based on publicly available national notification data for 2023. 23 Two additional exploratory costs extrapolations were undertaken using publicly available iGAS case for Western Australian in 2023 which stratified cases by location or First Nations status. 24 The first used the distribution of cases by locality to adjust the estimated healthcare costs by applying rurality weightings for iGAS cases in remote (MM6; 140%) and very remote (MM7; 150%) areas within Western Australia based on the Modified Monash Model. 25 The second exploratory extrapolation used the distribution of cases by First Nations status to adjust the estimated health care costs by applying a weighting of 367% to iGAS cases identified as First Nations in Western Australia. 26 As the weighting for providing healthcare to First Nations people includes rurality, these two estimates are not additive. To estimate the national cost of hospital care for iGAS across the lifespan, the cost of iGAS in the paediatric population in Australia was inflated by the CPI to 2023 calendar year and added to the estimated cost for adults produced by this study. 4 Assumptions underpinning the cost analysis and cost extrapolation are available in Tab S6. The economic evaluation has been reported consistent with CHEERs 2022 Checklist (Tab S7). 27 We used R (version 4.4.0, R Foundation for Statistical Computing, Vienna, Austria) for the epidemiological analyses and IBM SPSS Statistics, Version 28.09 for the economic analyses. Results Seventy-nine adult iGAS cases were treated at the RMH between 2018-2023 (Tab 1): 25 cases occurred before the COVID-19 pandemic (2018-2019), 18 during (2020-2022), and 36 after (2023) (Fig 1C). The median age of cases was 47 years (IQR: 36–65) and 61% (n=48) were male. Female cases were younger than male cases (median 39 years [IQR: 31–53] vs. 51 years [IQR: 42–65]) (Fig 1B). A quarter of all iGAS cases (n=20, 25%) had a documented history of injecting drug use (Tab 1). The most common manifestations were bacteraemia (60/79, 76%) and non-necrotising soft tissue infection (31/79, 39%). One third (n=29, 35%) of cases were admitted to the ICU, of whom 16 (55%) required intubation and 11 (38%) received IVIg. Cases with non-necrotising soft tissue infection were less likely to be admitted to ICU than other cases (p<0.001) (Tab 1). Of the 11 cases treated with IVIg, seven had STSS, three had necrotizing fasciitis and one had meningitis. More than half of all cases (n= 45, 57%) required at least one surgical intervention. One third of non-fatal cases (n=27/72; 38%) were discharged from hospital with a deficit and/or disability. Seven cases died (CFR: 9%, 95% CI: 4%–18%), including four of the 10 cases with STSS (CFR: 40%, 95% CI: 14%–73%). The median time from hospital admission to death was one day (range: 1–4 days). For cases that survived, the median length-of-stay during the index admission was 11 days (IQR: 6–19) (Tab 2) with longer length-of-stay associated with more severe outcomes. Cases discharged without deficit or disability had a median 8-day length-of-stay (IQR: 4–13), those with a deficit at discharge had a median 14-day length-of-stay (IQR: 12–26), and those discharged with a disability had a median 32-day length-of-stay (14–42). In the six-months post-discharge, 71% (n=56) of cases accessed healthcare services through RMH, including 28 (39%) who were readmitted with a median length-of-stay of 10 days (IQR: 1–13). Cases received a median of four different antibiotics (IQR: 3–5; Tab 1). More cases received vancomycin (72%), ceftriaxone (66%) or meropenem/piperacillin-tazobactam (56%) than benzylpenicillin (52%) or amoxicillin/amoxicillin-clavulanate (53%). Of 72 survivors, 19 (26%) did not receive either benzylpenicillin or amoxicillin/amoxicillin-clavulanate. Two-thirds (66%) received clindamycin: 24/29 (83%) of ICU cases and 28/50 (56%) of non-ICU cases. Vancomycin use was most frequent on day 2 of hospital admission, clindamycin on day 3 and benzylpenicillin on day 4 (Fig 1A). emm -types Whole genome sequencing data were available for 67 (85%) of the cases (Fig S1A, Tab S1). The population was polyclonal with twenty-seven different emm -types identified, most commonly emm1 (17/67, 25%), emm77 (9, 13%) and emm 101 (5, 7%) (Tab S1). ICU admission was more common among cases infected with emm 1 than other emm- types (OR 5.4 [95% CI: 1.1–32.7], p=0.024) and emm 1 was responsible for half (5/10) of all STSS cases with WGS data available (Tab S1). No cases with documented injecting drug use were infected with emm 1 (Fig S1B, Tab S1). Of the seven fatal cases, four were infected with emm 1 (CFR 23.5%, 95% CI: 7.8%–50.2%) and one with each of emm 4, emm 101 and emm 114. Cost burden The estimated average iGAS disease-related healthcare cost per adult treated at the RMH from 2018–2023 was $63,662 (SD: $84,743; Tab 2), with a combined healthcare utilisation cost for the 79 patients of $5,029,305. Most costs (80%) were incurred during the index admission, followed by 18% of costs in the 6 months post index admission) and 2% of costs in the initial emergency department consultations (Tab 2). For fatal cases (n=7), the average health care cost was $14,286 (SD $14,544) per case, while for survivors (n=72) the average healthcare cost was $68,500 (SD $87,200) per case (Tab 3). Average healthcare costs for cases who had recovered at the time of hospital discharge were lower (mean $41,900 (SD $43,000)) than for those that were discharged with a deficit ($108,800 (SD $130,800)) or disability ($133,300 (SD $96,800)). Among survivors, cases that were admitted to the ICU had higher healthcare cost (average $99,426 (SD $73,090)) than those who were not admitted to the ICU ($55,548 (SD $90,663)) (Tab 3 ). National cost burden extrapolation The estimated national healthcare cost burden for adults with iGAS in 2023 was $117.5 million (Tab S2). People aged 40-59 years (incidence 9.7 per 100,000; 29% of the impacted population) and 60-79 years (incidence 15.3 per 100,000; 34% of the impacted population) had the highest cost burden (Tab S2). The estimated total healthcare cost of treating males was $63.6 million, compared to $53.9 million for females. New South Wales, the most populous Australian state, had the highest number of notified iGAS cases in 2023 (707) and the highest estimated total healthcare costs for treating iGAS ($38.1 million) while the Northern Territory, the jurisdiction with the highest proportion of First Nations people (19%), 28 had the highest iGAS incidence among adults (61.0 per 100,000) with an estimated total cost of $6.1 million (Fig 2 and Tab S3). In 2023, the national healthcare cost burden for paediatric iGAS was $7.2 million (2018 cost burden inflated by CPI). 4 Therefore, in 2023, across the lifespan, the national healthcare cost burden for iGAS was $124.7 million. Explorative extrapolation for Western Australia The total healthcare cost of treating iGAS within Western Australia, without consideration of the additional cost of providing care to remote-living or First Nations people, was $12.0 million in 2023. The extrapolation that accounted for rurality resulted in an 8% increase in the total healthcare cost (to $13.0 million)(Tab S4) and the extrapolation that accounted for providing care to First Nations people resulted in a 60% increase in the total healthcare cost (to $19.2 million)(Tab S5). Discussion This audit of 79 iGAS cases presenting for care at RMH during 2018–2023 highlights the severity of iGAS and the very high cost of providing healthcare to iGAS cases in Australia. iGAS was fatal for 9% of cases, a third were admitted to the ICU and more than a third of non-fatal cases were discharged with a deficit or disability. The average healthcare cost of iGAS at the RMH including any re-admissions or outpatient services within six months was $63,662 (SD $84,743) per case. Cost per case varied significantly by outcome reflecting the length-of-stay for each outcome category. Fatal cases had the lowest costs because length-of-stay prior to death was so short (maximum 4 days) while those that were discharged with a disability had the highest costs. Despite being a rare disease, the nationwide healthcare cost burden for adult iGAS cases in 2023 was conservatively estimated to be $117.5 million. Directly comparable costings from other countries are not available. However, Cannon et al found a disproportionate percentage (14.1%) of all healthcare expenditure in New Zealand devoted to treating S. pyogenes infections were used to treat iGAS, underscoring the financial burden of this condition. 2 The true cost of healthcare to treat adult iGAS cases may be considerably higher than our estimation as we only included healthcare costs incurred at a single hospital with a follow-up period limited to six months. Costs of care beyond six months or at other health services were not captured, nor were the broader societal costs such as lost employment productivity. Further, the cost data used for this estimate do not reflect the additional costs of providing healthcare to remote-living or First Nations people. The additional exploratory analyses for Western Australia highlight that both these factors could have a significant impact on the overall cost of healthcare for iGAS in Australia. This is particularly important given the disproportionate burden of iGAS among First Nations people. 5,7,10 Although only half (52%) of iGAS cases at RMH received benzylpenicillin, this was substantially more than reported in the US (12%) and comparable to reported use in Finland when infectious diseases clinicians were consulted (59%). 13,29 The observed use of clindamycin and IVIg among iGAS cases at the RMH was high. Among ICU cases, 38% received IVIg at RMH compared to 8% in France and 26%–56% in Canada. 14–16 Two-thirds of all iGAS cases and 83% of ICU cases in our study were treated with clindamycin compared to 30% of all cases and 43% of ICU cases in the USA 29 and 56% of ICU cases in France. 14 No case within our study was treated with linezolid. In comparison, linezolid was used as an adjunctive therapy in 15% of ICU cases in France. 14 GAS retains near-universal susceptibility to linezolid while clindamycin resistance is increasing in GAS isolates and recent observational studies suggest it may be non-inferior to clindamycin as an adjunctive therapy for iGAS. 29,30 The observed emm -type distribution of S. pyogenes in this study is consistent with the comprehensive report on iGAS genomic epidemiology in Victoria by Morris et al. 20 Our study, however, matched the WGS data with detailed clinical data and we found emm 1 type was associated with a five-fold increase in odds of ICU admission and a higher CFR (23.5% vs 9.0%) than iGAS caused by other emm types. These findings are consistent with a study in Finland that found higher CFR for emm1 iGAS. 31 To our knowledge, this is the first study to provide an estimate of the cost of care for adult iGAS cases in Australia. This data will be important for health technology assessments, including cost-benefit analysis of any potential preventive therapies for iGAS, such as vaccines in development. Furthermore, by including detailed clinical data and WGS we have been able to report on the use of benzylpenicillin and adjunctive therapies to treat iGAS and investigate the relationships between disease severity and emm -type. This study has several limitations. First, the sample size for our study is small and access to individual patient-level data is restricted to a single health service (RMH). It is, therefore, not representative of all Victorian or Australian adult iGAS cases. Second, clinical and demographic data were collected by reviewing electronic health records which limited the completeness of demographic information available: important information such as duration of antibiotic treatment and intravenous drug use may not have been consistently recorded. Conclusions Our findings demonstrate the significant health and financial burden of iGAS in Australia. These findings support the case for investment in both prevention of iGAS (e.g. a GAS vaccine) and studies to establish the optimal treatment of iGAS to reduce the impact of this devastating disease. Declarations Ethics approval and consent to participate Ethics approval was obtained from the Royal Melbourne Hospital Human Research Ethics Committee (HREC/49200/MH-2018). The Royal Melbourne Hospital Human Research Committee provided a waiver of informed consent to complete this research. All methods were carried out in accordance with relevant guidelines and regulations, including the Declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials The clinical data that support the findings of this study are available from the Victorian Department of Health but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Victorian Department of Health. Whole genome sequence reads from Streptococcus pyogenes isolates analysed in this study are deposited in the National Centre for Biotechnology Information (NCBI) Sequence Read Archive (SRA) under the BioProject PRJNA857543. Competing interests Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding Katherine B Gibney received financial support from The Royal Australasian College of Physicians, the Australian Government Department of Health and Aged Care and The University of Melbourne. Norelle Sherry, Jake A Lacey and Sandra A Johnson received financial support from the State Government of Victoria. Authors’ contributions JJG: Formal analysis, Writing (Original Draft), Writing (Review & Editing), Visualization SLW: Formal analysis, Writing (Original Draft), Writing (Review & Editing) EC: Investigation, Validation, Writing (Review & Editing) JAL: Formal analysis, Writing (Review & Editing) SAJ: Investigation, Validation NK: Investigation T-Y H: Investigation JS: Supervision, Writing (Review & Editing) NWC: Methodology, Supervision, Writing (Review & Editing) NS: Supervision, Writing (Review & Editing) NKB: Methodology, Supervision, Writing (Review & Editing) KBG: Conceptualization, Methodology, Data Curation, Writing (Review & Editing), Supervision, Project administration, Funding acquisition Acknowledgements We thank Jeffrey Ong (Health Intelligence, RMH) for extracting hospital cost of care data for this study; the Victorian Department of Health for providing Whole Genome Sequence data for included cases; and Jeni Mitchell, Clinical Research Nurse (Victorian Infectious Diseases Service, RMH) for support setting up the study. Microbiological Diagnostic Unit Public Health Laboratory is funded by the Victorian Department of Health. References for adults (≥18 years) in Australia in 2023. 1. Steer AC, Lamagni T, Curtis N, Carapetis JR. Invasive group A streptococcal disease epidemiology, pathogenesis and management. Drugs 2012; 72: 1213–27. 2. Cannon JW, Zhung J, Bennett J, et al. The economic and health burdens of diseases caused by group A Streptococcus in New Zealand. Int J of Infect Dis 2021; 103: 176–81. 3. Oliver J, Thielemans E, McMinn A, et al. Invasive group A Streptococcus disease in Australian children: 2016 to 2018 – a descriptive cohort study. BMC Public Health 2019; doi: 10.1186/s12889-019-8085-2. 4. Brusco NK, Oliver J, McMinn A, Steer A, Crawford N. The cost of care for children hospitalised with invasive group A streptococcal disease in Australia. BMC Health Serv Res 2021; doi: 10.1186/s12913-021-07265-8. 5. Wright CM, Moorin R, Pearson G, et al. Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people. Med J Aust 2021; 215: 36–41. 6. Dunne E, Hutton S, Peterson E, et al. Increasing incidence of invasive group A Streptococcus disease, Idaho, USA, 2008–2019. Emerg Infect Dis 2022; 28:1785–95. 7. Tyrrell G, Bell C, Bill L, Fathima S. Increasing incidence of invasive group A Streptococcus disease in First Nations population, Alberta, Canada, 2003–2017. Emerg Infect Dis 2021;27: 443–51. 8. Abo YN, Oliver J, McMinn A, et al. Increase in invasive group A streptococcal disease among Australian children coinciding with northern hemisphere surges. Lancet Reg Health West Pac 2023; doi: 10.1016/j.lanwpc.2023.100873. 9. Tomidis Chatzimanouil MK, Rößler S, Nurjadi D, et al. Post-COVID-19-pandemic changes and clinical characteristics of invasive group a streptococcal infections from 2015 to 2023. Infection 2024; doi: 10.1007/s15010-024-02413-8. 10. Birrell JM, Boyd R, Currie BJ, et al. Invasive group A streptococcal disease in the Northern Territory and the impact of melioidosis antibiotic prophylaxis. Med J Aust 2022; 217: 544–5. 11. Valenciano SJ, Onukwube J, Spiller MW, et al. Invasive group A streptococcal infections among people who inject drugs and people experiencing homelessness in the United States, 2010–2017 . Clin Infect Dis 2021 ; 73: e3718–26. 12. Goldsmith JJ, Vu C, Zhu Z, MacLachlan JH, et al. The associations between invasive group A streptococcal disease and infection with influenza, varicella, or hepatitis C viruses: A data linkage study, Victoria, Australia. Int J Infect Dis 2024; doi: 10.1016/j.ijid.2024.02.012. 13. Vilhonen J, Vuopio J, Vahlberg T, el al. Group A streptococcal bacteremias in southwest Finland 2007–2018: epidemiology and role of infectious diseases consultation in antibiotic treatment selection. Eur J Clin Microbiol Infect Dis 2020; 39: 1339–48. 14. Orieux A, Prevel R, Dumery M, et al. Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study). Crit Care 2024; doi: 10.1186/s13054-023-04774-2. 15. Couture-Cossette A, Carignan A, Mercier A, et al. Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016. PLoS One 2018; doi: 10.1371/journal.pone.0206289 16. Mehta S, McGeer A, Low DE, et al. Morbidity and mortality of patients with invasive group A streptococcal infections admitted to the ICU. Chest 2006; 130: 1679–86. 17. Therapeutic Guidelines. Antibiotic. Melbourne, 2019. https://www.tg.org.au (viewed 2024 Oct 2024). 18. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42(2):377–81. 19. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform 2019; doi: 10.1016/j.jbi.2019.103208. 20. Morris JM, Lacey JA, Stevens K, et al. Genomic interrogation of invasive group A Streptococcus (iGAS) epidemiology and COVID-19 impacts in Victoria, Australia: a 6-year retrospective study. Lancet Reg Health West Pac 2025; doi : 10.1016/j.lanwpc.2025.101467. 21. Centre for Communicable Diseases and Prevention. Streptococcal Toxic Shock Syndrome (STSS) ( Streptococcus pyogenes ) 2010 case definition, 2016. https://ndc.services.cdc.gov/case-definitions/streptococcal-toxic-shock-syndrome-2010/ (viewed Oct 2024). 22. Reserve Bank of Australia. Inflation calculator, 2024. https://www.rba.gov.au/calculator (viewed Sep 2024). 23. Australian Government Department of Health and Aged Care. National communicable diseases surveillance dashboard, 2024. https://nindss.health.gov.au/pbi-dashboard (viewed Sep 2024). 24. Government of Western Australia Department of Health. Notifiable infectious disease dashboard, 2024. https://www.health.wa.gov.au/Articles/N_R/Notifiable-infectious-disease-dashboard (viewed Oct 2024). 25. Australian Government Department of Health and Aged Care. Modified Monash Model. 2023. 26. Ong KS, Kelaher M, Anderson I, Carter R. A cost-based equity weight for use in the economic evaluation of primary health care interventions: case study of the Australian Indigenous population. Int J Equity Health 2009; doi: 10.1186/1475-9276-8-34. 27. Husereau D, Drummond M, Augustovski F, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 explanation and elaboration: a report of the ISPOR CHEERS II Good Practices Task Force. Value Health 2022; 25: 10–31. 28. Australian Bureau of Statistics. Estimates of Aboriginal and Torres Strait Islander Australians. Canberra; 2021. https://www.abs.gov.au/statistics/people/aboriginal-and-torres-strait-islander-peoples/estimates-aboriginal-and-torres-strait-islander-australians/latest-release (viewed Nov 2024). 29. Babiker A, Li X, Lai YL, Strich JR, et al. Effectiveness of adjunctive clindamycin in β-lactam antibiotic-treated patients with invasive β-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study. Lancet Infect Dis 2021; 21: 697–710. 30. Heil EL, Kaur H, Atalla A, et al. Comparison of adjuvant clindamycin vs linezolid for severe invasive group A Streptococcus skin and soft tissue infections. Open Forum Infect Dis 2023; doi: 10.1093/ofid/ofad588 31. Siljander T, Lyytikäinen O, Vähäkuopus S, et al. Epidemiology, outcome and emm types of invasive group A streptococcal infections in Finland. Eur J Clin Microbiol Infect Dis 2010; 29: 1229–35. Abbreviations CFR – case fatality rate CI – confidence interval CPI – cost price index ICU – intensive care unit iGAS – invasive group A streptococcal IVIg – intravenous immunoglobulin IQR – interquartile range PWID – people who inject drugs RMH – Royal Melbourne Hospital SD – standard deviation STSS – streptococcal toxic shock syndrome WGS – whole genome sequencing Tables Table 1: Demographic and clinical characteristics of adults (≥18 years) with iGAS by ICU admission, RMH 2018–2023 Characteristic Overall a N = 79 Non-ICU admissions a N = 50 ICU admissions a N = 29 p-value d Age in years, median (IQR) 47 (36,65) 46 (33,68) 47 (39,63) >0.9 Sex 0.9 Female 31 (39%) 20 (40%) 11 (38%) Male 48 (61%) 30 (60%) 18 (62%) Risk factors Intravenous drug use 20 (25%) 14 (28%) 6 (21%) 0.5 Diabetes 14 (18%) 11 (22%) 3 (10%) 0.2 Manifestations b Bacteraemia with or without focus 60 (76%) 36 (72%) 24 (83%) 0.3 Non-necrotizing soft tissue infection 31 (39%) 28 (56%) 3 (10%) <0.001 Osteomyelitis or septic arthritis 17 (22%) 14 (28%) 3 (10%) 0.07 Pneumonia or empyema 14 (18%) 5 (10%) 9 (31%) 0.02 Necrotizing soft tissue infection 12 (15%) 4 (8.0%) 8 (28%) 0.03 Streptococcal toxic shock syndrome (STSS) 10 (13%) 0 (0%) 10 (34%) <0.001 Other 4 (5.1%) 1 (2.0%) 3 (10%) 0.14 Outcome of index hospital admission <0.001 Recovered 45 (57%) 35 (70%) 10 (34%) Deficit c 20 (25%) 12 (24%) 8 (28%) Disability c 7 (8.9%) 3 (6.0%) 4 (14%) Deceased 7 (8.9%) 0 (0%) 7 (24%) Antibiotic therapies Number of antibiotics (IQR) 4 (3, 5) 4 (3, 5) 5 (4, 6) 0.02 Vancomycin 57 (72%) 31 (62%) 26 (90%) 0.01 Ceftriaxone 52 (66%) 28 (56%) 24 (83%) 0.02 Clindamycin 52 (66%) 28 (56%) 24 (83%) 0.02 Meropenem or piperacillin-tazobactam 44 (56%) 20 (40%) 24 (83%) <0.001 Amoxicillin or amoxicillin-clavulanate 42 (53%) 33 (66%) 9 (31%) 0.003 Benzylpenicillin 41 (52%) 25 (50%) 16 (55%) 0.7 Adjunctive therapies Surgical intervention 45 (57%) 27 (54%) 18 (62%) 0.5 Steroids 24 (30%) 9 (18%) 15 (52%) 0.002 Intravenous immunoglobulin (IVIg) - - 11 (38%) Inotropes - - 23 (79%) Vasopressors - - 13 (45%) Intubation - - 16 (55%) a n(%) b Cases may have more than one manifestation. Eight cases had bacteraemia without focus. c Deficit is defined as a physical impairment anticipated to improve post-discharge while disability is defined as a permanent physical impairment. d Wilcoxon rank sum test; Pearson’s Chi-squared test Table 2: Resource unit definition, number of cases whose treatment accrued costs against a resource category, cost per case and total cost for each resource in 2023 AUD Resource category Unit definition Number of cases that accrued costs ¶ n(%) Healthcare costs Mean (SD) Total costs across all cases (n=79) Per cases exposed to care element costs ¶ Per case (n=79) ED Admission ED costs preceding index admission 73 § (92%) $1,359 ($947) § $1,359 ($947) § $99,187 § Index Admission All costs associated with index admission 79 (100%) $51,056 ($77,732) ‡ $51,056 ($77,732) ‡ $4,033,444‡ Acute ward admission Acute ward admission, includes medical and nursing utilisation. 65 (98%) ‡ $17,052 ($21,363) $16,793 ($21,301) ‡ CCU admission CCU costs associated with index admission 1 (2%) ‡ $9,984 (N/A) $151 ($1229) ‡ ICU admission ICU costs associated with index admission 24 (36%) ‡ $24,046 ($23,178) $8,744 ($18,054) ‡ HITH admission HITH costs associated with index admission 9 (14%) ‡ $6,793 ($4017) $926 ($2,739) ‡ Allied health utilisation Allied health costs associated with index admission 65 (98%) ‡ $1,144 ($2042) $1,127 ($2,031) ‡ Imaging utilisation Imaging costs associated with index admission 44 (67%) ‡ $1,136 ($1,021) $758 ($990) ‡ Pathology utilisation Pathology costs associated with index admission 64 (97%) ‡ $2,070 ($2,448) $2,007 ($2,436) ‡ Pharmacy utilisation Pharmacy costs associated with index admission 66 (100%) ‡ $1,551 ($1635) $1,551 ($1,635) ‡ Theatre utilisation Theatre and surgery costs associated with index admission 36 (55%) ‡ $11,452 ($14,046) $6,246 ($11,800) ‡ Other Any other index admission costs not previously specified. 65 (98%) ‡ $5,771 ($6,981) $5,684 ($6,963) ‡ Hospital utilisation within 6 months of index admission Any costs incurred at index hospital within 6 months of index admission. 56 (71%) Ò $16,012 ($41,443) À $11,350 ($35,562) Ò $896,675 Ò Re-admissions to the index hospital Includes all costs associated with emergency and inpatient (acute and subacute) admissions 33 (42%) $24,778 ($51,643) $10,624 ($35,293) Outpatient services Includes all costs associated with outpatient care 43 (54%) $1,333 ($2,061) $726 ($1,654) Total healthcare utilisation Combines cost of ED admission, index admission and 6 month follow up 79 (100%) $63,662 ($84,743) $63,662 ($84,743) ƒ $5,029,305 ¶ Cases data presented for cases with costs/healthcare utilisation for each resource category. ‡ Modelled data for costs n=13 of total sample, therefore total cases n=66 with cost data provided. ƒ The average cost dropped to $53,866 (SD $54,379) when cases with a LoS >120 days during either their index admission or the 6-month follow-up period were excluded. Cost distribution by resource category did not change. § Missing data n=6 Ò Modelled data for costs within 6 months n=14, CCU: Coronary care unit; ICU: Intensive care unit; HITH: Hospital in the home Table 3: Overall healthcare utilisation and cost per subgroup and resource unit in 2023 AUD, mean (SD) ED utilisation costs Index admission length-of-stay (days) Index admission costs Hospital costs within 6 months § Total healthcare costs Disease Outcome Fatal ¶ (n= 7) $1075 ($500) 1.71 (1.11) $13,211 ($14,186) $0 ($0) $14,286 ($14544) Survived (n=72) $1,389 ($980) ò 16.58 (22.89) $54,736 ($80,411) $12,454 ($37,086) $68,463 ($87,223) Recovered (n= 46) $1,628 ($1,016) ƒ 10.62 (11.28) $33,285 ($39,962) $7,150 ($14,303) $41,921 ($42,964) Deficit (n= 19) $1,162 ($811) ‡ 26.65 (37.03) $82,109 ($124,700) $25,684 ($66,796) $108,832 ($130,815) Disability (n= 7) $507 ($373) 28.48 (19.33) $121,397 ($82,475) $11,400 ($24,178) $133,303 ($96,843) Age 18-39 years (n=21) $1,510 ($953)ˆ 12.12 (10.82) $45,821 ($53,439) $5,841 ($18,948) $53,099 ($55,672) 40-59 years (n=33) $1,192 ($867) ƒ 20.61 (32.05) $69,602 ($108,267) $8,559 ($17,627) $79,208 ($111,605) 60-79 years (n=10) $1,150 ($725) 14.95 (8.39) $46,108 ($31,309) $38,281 ($88,499) $85,539 ($80,825) 80 years and over (n=8) $2,202 ($1,459)ˆ 13.75 (6.77) $27,600 ($18,737) $13,596 ($16,648) $43,123 ($23,825) Gender Female (n= 29) $1,708 ($973) ƒ 13.11 (9.18) $36,041 ($23,597) $13,721 ($53,270) $51,234 ($52,155) Male (n= 43) $1,194 ($943) ‡ 18.93 (28.56) $67,344 ($100,773) $11,599 ($20,771) $80,082 ($103,461) Admission status ICU admission (n=21) c $1,126 ($840) ƒ 19.68 (17.29) $89,864 ($67,017) $8,596 ($17,629) $99,426 ($73,790) Non-ICU admission (n= 50) $1,487 ($1,018) ‡ 15.18 (25.11) $39,803 ($82,328) $14,318 ($43,048) $55,548 ($90,663) Surgery related to illness Yes (n= 46) À $1,080 ($737) ƒ 20.78 (27.48) $69,122 ($94,556) $10,166 ($20,233) $80,274 ($97,365) No (n= 26) $1,929 ($1,125) ‡ 9.15 (6.29) $29,283 ($34,860) $16,502 ($56,058) $47,566 ($61,901) § Hospital costs within 6 months of discharge from index admission, including re-admissions to the index hospital (emergency department, acute and subacute) and outpatient services. ¶ Death occurred during index admission. Cases that died during the index admission were excluded from the sub-group analysis of age, gender, disease severity and surgery related to illness. ò Missing data n=6. ƒ Missing data n= 4. ‡ Missing data n= 2. ˆMissing data n=1 À n=2 cases had procedures at bedside that were included as ‘surgery’, theatre resource costs were not allocated as they were included as part of the acute ward admission costs. c n=1 case was excluded from this sub-group analysis. This case had a disrupted admission at the index hospital and was transferred to a different hospital during the episode of care at the index hospital. The significant portion of the index admission was the second part of the admission to the index hospital, this data is what was used for the economic evaluation of the study. Additional Declarations No competing interests reported. Supplementary Files supplementarymaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 17 Mar, 2025 Reviewers invited by journal 03 Mar, 2025 Editor assigned by journal 25 Feb, 2025 Editor invited by journal 04 Feb, 2025 Submission checks completed at journal 30 Jan, 2025 First submitted to journal 30 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5847008","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":423738308,"identity":"e252f6de-12d9-49ea-b113-6830cb615a40","order_by":0,"name":"Jessie J Goldsmith","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYBACxgYg8aCCgYENyD4MEyCsJeEMWAsDcVrAILENQhOnhbl/+cUHifMO5/GJHT5wuIDBRnbDAeZnEngdNuNNsUHitsPFbNJpCYdnMKQZbzjAZkZAy5k0CaCWxDbpHIPDPAyHEzccYCBGyxyQlvwPQC3/gVrYv+HX0t9+TCKxAWwLA1DLAaAWHkK28DAbJBxLB2pJMzg8wyDZeOZhnmILfFoM+48/fPChxjpx/uzkh48LKuxk+463b7yBV8uMHAMkLojNjE89EMjzH39AQMkoGAWjYBSMeAAAP8BRlSKkclUAAAAASUVORK5CYII=","orcid":"","institution":"University of Melbourne","correspondingAuthor":true,"prefix":"","firstName":"Jessie","middleName":"J","lastName":"Goldsmith","suffix":""},{"id":423738309,"identity":"ad01bc44-2e37-4f1c-913e-7fca23053a05","order_by":1,"name":"Sara L Whittaker","email":"","orcid":"","institution":"Monash University","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"L","lastName":"Whittaker","suffix":""},{"id":423738310,"identity":"b7f65965-bfe1-4779-be95-0cf6c46373ce","order_by":2,"name":"Eddie Chan","email":"","orcid":"","institution":"The Royal Melbourne Hospital","correspondingAuthor":false,"prefix":"","firstName":"Eddie","middleName":"","lastName":"Chan","suffix":""},{"id":423738311,"identity":"f430b5c2-d832-45d7-9186-631f926cccab","order_by":3,"name":"Jake A Lacey","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Jake","middleName":"A","lastName":"Lacey","suffix":""},{"id":423738312,"identity":"086c7759-d24b-4e91-9153-251b9ba61679","order_by":4,"name":"Sandra A Johnson","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Sandra","middleName":"A","lastName":"Johnson","suffix":""},{"id":423738314,"identity":"0fbc2fc4-1a53-4c7a-8982-2943db1bf252","order_by":5,"name":"Najma Kori","email":"","orcid":"","institution":"Universiti Kebangsaan","correspondingAuthor":false,"prefix":"","firstName":"Najma","middleName":"","lastName":"Kori","suffix":""},{"id":423738316,"identity":"b52b5df6-ebd2-4e80-82ec-048c513b470c","order_by":6,"name":"Te-Yu Hung","email":"","orcid":"","institution":"Royal Darwin Hospital","correspondingAuthor":false,"prefix":"","firstName":"Te-Yu","middleName":"","lastName":"Hung","suffix":""},{"id":423738317,"identity":"4bd82d41-9af0-46ad-90de-afe78fbf40cf","order_by":7,"name":"Janet Strachan","email":"","orcid":"","institution":"Victorian Department of Health","correspondingAuthor":false,"prefix":"","firstName":"Janet","middleName":"","lastName":"Strachan","suffix":""},{"id":423738319,"identity":"7b3912f6-cac0-4934-a384-28825b551cfd","order_by":8,"name":"Nigel W Crawford","email":"","orcid":"","institution":"Royal Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nigel","middleName":"W","lastName":"Crawford","suffix":""},{"id":423738321,"identity":"64e62a04-1711-4714-bd69-d44dd3a758e8","order_by":9,"name":"Norelle Sherry","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Norelle","middleName":"","lastName":"Sherry","suffix":""},{"id":423738323,"identity":"e53cb0cd-1d57-4bf9-a481-e43fde6f9b3a","order_by":10,"name":"Natasha K Brusco","email":"","orcid":"","institution":"Monash University","correspondingAuthor":false,"prefix":"","firstName":"Natasha","middleName":"K","lastName":"Brusco","suffix":""},{"id":423738324,"identity":"c9f37883-cff6-4f3d-aa7f-99dce3618498","order_by":11,"name":"Katherine B Gibney","email":"","orcid":"","institution":"University of Melbourne","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"B","lastName":"Gibney","suffix":""}],"badges":[],"createdAt":"2025-01-17 07:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5847008/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5847008/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77807717,"identity":"cbf9f674-442b-48bf-b3b6-f9cab2d88016","added_by":"auto","created_at":"2025-03-05 17:36:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1420108,"visible":true,"origin":"","legend":"\u003cp\u003eAdult (≥18 years) iGAS cases treated at the RMH between 2018 and 2023 by (A) proportion treated in the first ten days by type of antibiotic (B) by age group and biological sex and (C) by year and admissions status.\u003c/p\u003e","description":"","filename":"Fig1flat.png","url":"https://assets-eu.researchsquare.com/files/rs-5847008/v1/327e4a8be0257fe771dbefbb.png"},{"id":77807716,"identity":"f968eae7-4452-46de-a4d9-7739352bc6bf","added_by":"auto","created_at":"2025-03-05 17:36:19","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":570735,"visible":true,"origin":"","legend":"\u003cp\u003eEstimated healthcare cost of iGAS by jurisdiction ($m) and estimated iGAS incidence rate per 100,000 people for adults (≥18 years) in Australia in 2023.\u003c/p\u003e","description":"","filename":"Fig2flat.png","url":"https://assets-eu.researchsquare.com/files/rs-5847008/v1/3d52e313fefadab959e1ecd9.png"},{"id":77809053,"identity":"cf37ce78-7d00-4473-b408-98ad391afa79","added_by":"auto","created_at":"2025-03-05 17:44:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2187751,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5847008/v1/c4f3c5ae-678b-4aad-9480-e3de0883c08f.pdf"},{"id":77807718,"identity":"3c50dc55-a915-4ffe-b384-1b049b7811d7","added_by":"auto","created_at":"2025-03-05 17:36:19","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":323161,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5847008/v1/3dd6fdcdaa93902dcd459766.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Invasive group A streptococcal infections in Australian adults – a descriptive cohort and cost burden study","fulltext":[{"header":"Background","content":"\u003cp\u003eInvasive group A \u003cem\u003eStreptococcus\u003c/em\u003e (iGAS) is a rare, severe and rapidly progressive disease caused by \u003cem\u003eStreptococcus pyogenes\u003c/em\u003e,\u003csup\u003e1\u003c/sup\u003e with\u0026nbsp;a variety of clinical syndromes including sepsis, necrotising fasciitis, and streptococcal toxic shock syndrome (STSS). Even with prompt antibiotics and supportive treatments, iGAS case-fatality-rates (CFR) in well-resourced settings range from 8%\u0026ndash;16%\u003csup\u003e1\u003c/sup\u003e and a significant proportion of survivors are discharged from hospital with a physical impairment.\u003csup\u003e2,3\u003c/sup\u003e The healthcare costs associated with treating paediatric iGAS in Australia was estimated to be $6.2 million in 2019.\u003csup\u003e4\u003c/sup\u003e However, the healthcare cost of iGAS in adults in Australia is not known.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrior to the emergence of COVID-19, the incidence of iGAS was rising in many high-income countries, including the USA, New Zealand, Canada, and Australia.\u003csup\u003e2,5\u0026ndash;7\u003c/sup\u003e Following the easing of COVID-19 restrictions there was a global surge in iGAS, with disease incidence surpassing the long-term trend.\u003csup\u003e8,9\u003c/sup\u003e The burden of iGAS is inequitable. In Australia and other regions, First Nations people and people who inject drugs (PWID) are four- to eight-fold\u003csup\u003e5,7,10\u003c/sup\u003e and three to 14-fold,\u003csup\u003e11,12\u003c/sup\u003e respectively, more likely to be diagnosed with iGAS than other populations.\u003c/p\u003e\n\u003cp\u003eThere is evidence of substantial variation in clinical management of iGAS, both across jurisdictions and between individual clinicians, despite penicillin being the recommended targeted treatment \u003csup\u003e1\u003c/sup\u003e. A Finnish study of GAS bacteraemia cases found for cases not requiring admission to an intensive care unit (ICU), penicillin use was higher for cases who received an infectious diseases clinician consultation compared to those who did not (59% vs. 21%).\u003csup\u003e13\u003c/sup\u003e There is also considerable variation in the use of adjunctive therapies such as clindamycin, linezolid and intravenous immunoglobulin (IVIg),\u003csup\u003e14\u0026ndash;16\u003c/sup\u003e for which\u0026nbsp;the evidence supporting their use is equivocal.\u003csup\u003e17\u003c/sup\u003e At present there is limited available evidence regarding clinical management of iGAS in Australia.\u003c/p\u003e\n\u003cp\u003eThe growing incidence of iGAS and the inequitable burden on First Nations people are reasons to prioritise investment in research to improve prevention and management of iGAS. Quantifying the hospital cost burden for adult iGAS cases and describing the variability of treatment approach in Australia provides evidence to support this argument. Here we describe the epidemiology, clinical course, genomics, and healthcare cost burden of iGAS amongst adult cases presenting to the Royal Melbourne Hospital (RMH) during 2018-2023 and extrapolate the costs to determine the national healthcare cost burden for adults with iGAS in Australia in 2023.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThe RMH is an adult quaternary hospital in Victoria, Australia, with a 42-bed intensive care unit (ICU). iGAS cases aged \u0026ge;18 years and diagnosed from 01/01/2018\u0026ndash;31/12/2023, where\u003cem\u003e\u0026nbsp;S. pyogenes\u003c/em\u003e was cultured from a normally sterile site, were included. This study was approved by the RMH Human Research Ethics Committee (HREC/49200/MH-2018).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eData collection\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003ePatient data were extracted from the electronic medical records of their index hospital admission for iGAS by infectious diseases physicians to a study REDCap (Research Electronic Data Capture) database hosted at The University of Melbourne.\u003csup\u003e18,19\u003c/sup\u003e We recorded demographics, comorbidities (including injecting drug use), iGAS manifestations and outcomes, length-of-stay, ICU admission, surgical interventions, and use of antibiotics and IVIg. Outcomes among survivors were defined at the time of hospital discharge as disability (permanent physical impairment), deficit (physical impairment anticipated to improve post-discharge), or no disability/deficit.\u003c/p\u003e\n\u003cp\u003eWhole genome sequencing (WGS) of a single \u003cem\u003eS. pyogenes\u003c/em\u003e isolate from included iGAS cases was undertaken prospectively by the Microbiological Diagnostic Unit Public Health Laboratory according to accredited laboratory workflows using the Illumina NextSeq platform. For further information refer to the paper by Morris et.al.\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIndividual patient cost-of-care data for included iGAS cases were provided by the RMH Health Intelligence Unit. Clinical cost data included health care costs and utilization for the index iGAS admission at RMH (all included cases), and other costs of care delivered by RMH during the six-month period following the date of the index hospital admission for iGAS. Contacts comprised the index admission to RMH as well as all RMH services in the 6-months following the index admission, including investigations (laboratory tests, imaging), allied health visits, prescribed medications, hospital-in-the-home, re-admissions, and outpatient appointments. Cost data for each contact with the RMH were presented as a total, and by resource categories (\u0026lsquo;cost buckets\u0026rsquo;) including allied health, emergency department, ICU, imaging, medical, nursing, pathology, pharmacy and other. Other data included length-of-stay (in days) for the index admission and all re-admissions within six months.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eData analysis\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eCases were classified by whether they were admitted to the ICU and by the following iGAS manifestations: bacteraemia with or without focus, osteomyelitis or septic arthritis, STSS, pneumonia or empyema, necrotizing soft tissue infection, non-necrotizing soft tissue infection, and other. STSS was defined as an iGAS case with hypotension (systolic blood pressure \u0026lt;90 mmHg) and multi-organ involvement, according to the CDC\u0026rsquo;s STSS 2010 Case Definition\u003csup\u003e21\u003c/sup\u003e. Cases could have more than one manifestation. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic and clinical features and GAS \u003cem\u003eemm\u003c/em\u003e-types were described for iGAS cases and compared using the Wilcoxon rank sum test or Pearson chi-squared test.\u003c/p\u003e\n\u003cp\u003eAntibiotics were classified as empiric (broad spectrum antibiotics not specifically directed towards \u003cem\u003eS. pyogenes\u003c/em\u003e, including carbapenems, fourth generation cephalosporins, extended-spectrum penicillins, glycopeptides), directed (targeted to \u003cem\u003eS. pyogenes\u003c/em\u003e, including narrow spectrum penicillins, 2\u003csup\u003end\u003c/sup\u003e or 3\u003csup\u003erd\u003c/sup\u003e generation cephalosporins) or adjunctive (used to reduce toxin production, including clindamycin and linezolid), and their use was described over the first 10 days after hospital admission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor \u003cem\u003eemm\u003c/em\u003e-types with at least five cases, odds ratios (OR) by \u003cem\u003eemm\u003c/em\u003e-type were calculated according to need for ICU admission. The Bonferroni correction method was used to adjust p-values (calculated using Fisher\u0026rsquo;s exact test) and confidence intervals to account for multiple hypothesis testing.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCost burden\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eRMH cost data were matched to clinical case data.\u0026nbsp;The cost analysis presents the unit definition, unit cost, unit quantity and total cost for each resource (i.e. \u0026lsquo;cost buckets\u0026rsquo;), presented as a mean and standard deviation (SD). Each of the units were added together to present a per person cost for the index admission and the subsequent care in the 6 months post-discharge.\u0026nbsp;Where cost data were incomplete, average costs and the case\u0026rsquo;s reported length-of-stay and utilisation data were used to model the missing data. Individual case-level cost and utilisation data were analysed from a health system perspective. A sub-group analysis was completed excluding cases that died during the index admission. Opportunity costs were not included in this cost analysis. All costs were converted via Consumer Price Index (CPI)\u003csup\u003e22\u003c/sup\u003e to the 2023 calendar year and presented as $AUD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNational cost burden extrapolation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe national cost burden for all adult (\u0026ge;18 years) iGAS hospitalisations was estimated using extrapolation. The cost per case by gender and age produced in the cost analysis was multiplied by the incidence by age and gender for each Australian jurisdiction. For this extrapolation, incidence was based on publicly available national notification data for 2023.\u003csup\u003e23\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo additional exploratory costs extrapolations were undertaken using publicly available iGAS case for Western Australian in 2023 which stratified cases by location or First Nations status.\u003csup\u003e24\u003c/sup\u003e The first used the distribution of cases by locality to adjust the estimated healthcare costs by applying rurality weightings for iGAS cases in remote (MM6; 140%) and very remote (MM7; 150%) areas within Western Australia based on the Modified Monash Model.\u003csup\u003e25\u003c/sup\u003e The second exploratory extrapolation used the distribution of cases by First Nations status to adjust the estimated health care costs by applying a weighting of 367% to iGAS cases identified as First Nations in Western Australia.\u003csup\u003e26\u003c/sup\u003e As the weighting for providing healthcare to First Nations people includes rurality, these two estimates are not additive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo estimate the national cost of hospital care for iGAS across the lifespan, the cost of iGAS in the paediatric population in Australia was inflated by the CPI to 2023 calendar year and added to the estimated cost for adults produced by this study.\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAssumptions underpinning the cost analysis and cost extrapolation are available in Tab S6. The economic evaluation has been reported consistent with CHEERs 2022 Checklist (Tab S7).\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eWe used R (version 4.4.0, R Foundation for Statistical Computing, Vienna, Austria) for the epidemiological analyses and IBM SPSS Statistics, Version 28.09 for the economic analyses.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSeventy-nine adult iGAS cases were treated at the RMH between 2018-2023 (Tab 1): 25 cases occurred before the COVID-19 pandemic (2018-2019), 18 during (2020-2022), and 36 after (2023) (Fig 1C). The median age of cases was 47 years (IQR: 36\u0026ndash;65) and 61% (n=48) were male. Female cases were younger than male cases (median 39 years [IQR: 31\u0026ndash;53] vs. 51 years [IQR: 42\u0026ndash;65]) (Fig 1B). A quarter of all iGAS cases (n=20, 25%) had a documented history of injecting drug use (Tab 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most common manifestations were bacteraemia (60/79, 76%) and non-necrotising soft tissue infection (31/79, 39%). One third (n=29, 35%) of cases were admitted to the ICU, of whom 16 (55%) required intubation and 11 (38%) received IVIg. Cases with non-necrotising soft tissue infection were less likely to be admitted to ICU than other cases (p\u0026lt;0.001) (Tab 1). Of the 11 cases treated with IVIg, seven had STSS, three had necrotizing fasciitis and one had meningitis. More than half of all cases (n= 45, 57%) required at least one surgical intervention. One third of non-fatal cases (n=27/72; 38%) were discharged from hospital with a deficit and/or disability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeven cases died (CFR: 9%, 95% CI: 4%\u0026ndash;18%), including four of the 10 cases with STSS (CFR: 40%, 95% CI: 14%\u0026ndash;73%). The median time from hospital admission to death was one day (range: 1\u0026ndash;4 days). For cases that survived, the median length-of-stay during the index admission was 11 days (IQR: 6\u0026ndash;19) (Tab 2) with longer length-of-stay associated with more severe outcomes. Cases discharged without deficit or disability had a median 8-day length-of-stay (IQR: 4\u0026ndash;13), those with a deficit at discharge had a median 14-day length-of-stay (IQR: 12\u0026ndash;26), and those discharged with a disability had a median 32-day length-of-stay (14\u0026ndash;42). In the six-months post-discharge, 71% (n=56) of cases accessed healthcare services through RMH, including 28 (39%) who were readmitted with a median length-of-stay of 10 days (IQR: 1\u0026ndash;13). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCases received a median of four different antibiotics (IQR: 3\u0026ndash;5; Tab 1). More cases received vancomycin (72%), ceftriaxone (66%) or meropenem/piperacillin-tazobactam (56%) than benzylpenicillin (52%) or amoxicillin/amoxicillin-clavulanate (53%). Of 72 survivors, 19 (26%) did not receive either benzylpenicillin or amoxicillin/amoxicillin-clavulanate. Two-thirds (66%) received clindamycin: 24/29 (83%) of ICU cases and 28/50 (56%) of non-ICU cases. Vancomycin use was most frequent on day 2 of hospital admission, clindamycin on day 3 and benzylpenicillin on day 4 (Fig 1A).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eemm\u003c/u\u003e\u003c/em\u003e\u003cu\u003e-types\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWhole genome sequencing data were available for 67 (85%) of the cases (Fig S1A, Tab S1). The population was polyclonal with twenty-seven different \u003cem\u003eemm\u003c/em\u003e-types identified, most commonly \u003cem\u003eemm1\u003c/em\u003e (17/67, 25%), \u003cem\u003eemm77\u003c/em\u003e (9, 13%) and \u003cem\u003eemm\u003c/em\u003e101 (5, 7%) (Tab S1). ICU admission was more common among cases infected with \u003cem\u003eemm\u003c/em\u003e1 than other \u003cem\u003eemm-\u003c/em\u003etypes (OR 5.4 [95% CI: 1.1\u0026ndash;32.7], p=0.024) and \u003cem\u003eemm\u003c/em\u003e1 was responsible for half (5/10) of all STSS cases with WGS data available (Tab S1). No cases with documented injecting drug use were infected with \u003cem\u003eemm\u003c/em\u003e1 (Fig S1B, Tab S1). Of the seven fatal cases, four were infected with \u003cem\u003eemm\u003c/em\u003e1 (CFR 23.5%, 95% CI: 7.8%\u0026ndash;50.2%) and one with each of \u003cem\u003eemm\u003c/em\u003e4, \u003cem\u003eemm\u003c/em\u003e101 and \u003cem\u003eemm\u003c/em\u003e114.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eCost burden\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe estimated average iGAS disease-related healthcare cost per adult treated at the RMH from 2018\u0026ndash;2023 was $63,662 (SD: $84,743; Tab 2), with a combined healthcare utilisation cost for the 79 patients of $5,029,305. Most costs (80%) were incurred during the index admission, followed by 18% of costs in the 6 months post index admission) and 2% of costs in the initial emergency department consultations (Tab 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor fatal cases (n=7), the average health care cost was $14,286 (SD $14,544) per case, while for survivors (n=72) the average healthcare cost was $68,500 (SD $87,200) per case (Tab 3). Average healthcare costs for cases who had recovered at the time of hospital discharge were lower (mean $41,900 (SD $43,000)) than for those that were discharged with a deficit ($108,800 (SD $130,800)) or disability ($133,300 (SD $96,800)). Among survivors, cases that were admitted to the ICU had higher healthcare cost (average $99,426 (SD $73,090)) than those who were not admitted to the ICU ($55,548 (SD $90,663))\u0026nbsp;(Tab \u003cem\u003e3\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNational cost burden extrapolation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe estimated national healthcare cost burden for adults with iGAS in 2023 was $117.5 million (Tab S2). People aged 40-59 years (incidence 9.7 per 100,000; 29% of the impacted population) and 60-79 years (incidence 15.3 per 100,000; 34% of the impacted population) had the highest cost burden (Tab S2). The estimated total healthcare cost of treating males was $63.6 million, compared to $53.9 million for females. New South Wales, the most populous Australian state, had the highest number of notified iGAS cases in 2023 (707) and the highest estimated total healthcare costs for treating iGAS ($38.1 million) while the Northern Territory, the jurisdiction with the highest proportion of First Nations people (19%),\u003csup\u003e28\u003c/sup\u003e had the highest iGAS incidence among adults (61.0 per 100,000) with an estimated total cost of $6.1 million (Fig \u003cem\u003e2\u003c/em\u003e and Tab S3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn 2023, the national healthcare cost burden for paediatric iGAS was $7.2 million (2018 cost burden inflated by CPI).\u003csup\u003e4\u003c/sup\u003e Therefore, in 2023, across the lifespan, the national healthcare cost burden for iGAS was $124.7 million.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eExplorative extrapolation for Western Australia\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe total healthcare cost of treating iGAS within Western Australia, without consideration of the additional cost of providing care to remote-living or First Nations people, was $12.0 million in 2023. The extrapolation that accounted for rurality resulted in an 8% increase in the total healthcare cost (to $13.0 million)(Tab S4) and the extrapolation that accounted for providing care to First Nations people resulted in a 60% increase in the total healthcare cost (to $19.2 million)(Tab S5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis audit of 79 iGAS cases presenting for care at RMH during 2018\u0026ndash;2023 highlights the severity of iGAS and the very high cost of providing healthcare to iGAS cases in Australia. iGAS was fatal for 9% of cases, a third were admitted to the ICU and more than a third of non-fatal cases were discharged with a deficit or disability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe average healthcare cost of iGAS at the RMH including any re-admissions or outpatient services within six months was $63,662 (SD $84,743) per case. Cost per case varied significantly by outcome reflecting the length-of-stay for each outcome category. Fatal cases had the lowest costs because length-of-stay prior to death was so short (maximum 4 days) while those that were discharged with a disability had the highest costs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite being a rare disease, the nationwide healthcare cost burden for adult iGAS cases in 2023 was conservatively estimated to be $117.5 million. Directly comparable costings from other countries are not available. However, Cannon et al found a disproportionate percentage (14.1%) of all healthcare expenditure in New Zealand devoted to treating \u003cem\u003eS. pyogenes\u0026nbsp;\u003c/em\u003einfections were used to treat iGAS, underscoring the financial burden of this condition.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp; The true cost of healthcare to treat adult iGAS cases may be considerably higher than our estimation as we only included healthcare costs incurred at a single hospital with a follow-up period limited to six months. Costs of care beyond six months or at other health services were not captured, nor were the broader societal costs such as lost employment productivity. Further, the cost data used for this estimate do not reflect the additional costs of providing healthcare to remote-living or First Nations people. The additional exploratory analyses for Western Australia highlight that both these factors could have a significant impact on the overall cost of healthcare for iGAS in Australia. This is particularly important given the disproportionate burden of iGAS among First Nations people.\u003csup\u003e5,7,10\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAlthough only half (52%) of iGAS cases at RMH received benzylpenicillin, this was substantially more than reported in the US (12%) and comparable to reported use in Finland when infectious diseases clinicians were consulted (59%).\u003csup\u003e13,29\u003c/sup\u003e The observed use of clindamycin and IVIg among iGAS cases at the RMH was high. Among ICU cases, 38% received IVIg at RMH compared to 8% in France and 26%\u0026ndash;56% in Canada.\u003csup\u003e14\u0026ndash;16\u003c/sup\u003e Two-thirds of all iGAS cases and 83% of ICU cases in our study were treated with clindamycin compared to 30% of all cases and 43% of ICU cases in the USA\u0026nbsp;\u003csup\u003e29\u003c/sup\u003e and 56% of ICU cases in France.\u003csup\u003e14\u003c/sup\u003e No case within our study was treated with linezolid. In comparison, linezolid was used as an adjunctive therapy in 15% of ICU cases in France.\u003csup\u003e14\u003c/sup\u003e GAS retains near-universal susceptibility to linezolid while clindamycin resistance is increasing in GAS isolates and recent observational studies suggest it may be non-inferior to clindamycin as an adjunctive therapy for iGAS.\u003csup\u003e29,30\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe observed \u003cem\u003eemm\u003c/em\u003e-type distribution of \u003cem\u003eS. pyogenes\u0026nbsp;\u003c/em\u003ein this study is consistent with the comprehensive report on iGAS genomic epidemiology in Victoria by Morris et al.\u003csup\u003e20\u003c/sup\u003e Our study, however, matched the WGS data with detailed clinical data and we found \u003cem\u003eemm\u003c/em\u003e1 type was associated with a five-fold increase in odds of ICU admission and a higher CFR (23.5% vs 9.0%) than iGAS caused by other \u003cem\u003eemm\u003c/em\u003e types. These findings are consistent with a study in Finland that found higher CFR for emm1 iGAS.\u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the first study to provide an estimate of the cost of care for adult iGAS cases in Australia. This data will be important for health technology assessments, including cost-benefit analysis of any potential preventive therapies for iGAS, such as vaccines in development. Furthermore, by including detailed clinical data and WGS we have been able to report on the use of benzylpenicillin and adjunctive therapies to treat iGAS and investigate the relationships between disease severity and \u003cem\u003eemm\u003c/em\u003e-type.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the sample size for our study is small and access to individual patient-level data is restricted to a single health service (RMH). It is, therefore, not representative of all Victorian or Australian adult iGAS cases. Second, clinical and demographic data were collected by reviewing electronic health records which limited the completeness of demographic information available: important information such as duration of antibiotic treatment and intravenous drug use may not have been consistently recorded.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings demonstrate the significant health and financial burden of iGAS in Australia. These findings support the case for investment in both prevention of iGAS (e.g. a GAS vaccine) and studies to establish the optimal treatment of iGAS to reduce the impact of this devastating disease.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained from the Royal Melbourne Hospital Human Research Ethics Committee (HREC/49200/MH-2018). The Royal Melbourne Hospital Human Research Committee provided a waiver of informed consent to complete this research. All methods were carried out in accordance with relevant guidelines and regulations, including the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical data that support the findings of this study are available from the Victorian Department of Health but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Victorian Department of Health.\u003c/p\u003e\n\u003cp\u003eWhole genome sequence reads from Streptococcus pyogenes isolates analysed in this study are deposited in the National Centre for Biotechnology Information (NCBI) Sequence Read Archive (SRA) under the BioProject PRJNA857543.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKatherine B Gibney received financial support from The Royal Australasian College of Physicians, the Australian Government Department of Health and Aged Care and The University of Melbourne. Norelle Sherry, Jake A Lacey and Sandra A Johnson received financial support from the State Government of Victoria.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJJG: Formal analysis, Writing (Original Draft), Writing (Review \u0026amp; Editing), Visualization\u003c/p\u003e\n\u003cp\u003eSLW: Formal analysis, Writing (Original Draft), Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eEC: Investigation, Validation, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eJAL: Formal analysis, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eSAJ: Investigation, Validation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNK: Investigation\u003c/p\u003e\n\u003cp\u003eT-Y H: Investigation\u003c/p\u003e\n\u003cp\u003eJS: Supervision, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eNWC: Methodology, Supervision, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eNS: Supervision, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eNKB: Methodology, Supervision, Writing (Review \u0026amp; Editing)\u003c/p\u003e\n\u003cp\u003eKBG: Conceptualization, Methodology, Data Curation, Writing (Review \u0026amp; Editing), Supervision, Project administration, Funding acquisition\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Jeffrey Ong (Health Intelligence, RMH) for extracting hospital cost of care data for this study; the Victorian Department of Health for providing Whole Genome Sequence data for included cases; and Jeni Mitchell, Clinical Research Nurse (Victorian Infectious Diseases Service, RMH) for support setting up the study. Microbiological Diagnostic Unit Public Health Laboratory is funded by the Victorian Department of Health.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003efor adults (\u0026ge;18 years) in Australia in 2023.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Steer AC, Lamagni T, Curtis N, Carapetis JR. Invasive group A streptococcal disease epidemiology, pathogenesis and management. Drugs 2012; 72: 1213\u0026ndash;27.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Cannon JW, Zhung J, Bennett J, et al. The economic and health burdens of diseases caused by group A \u003cem\u003eStreptococcus\u003c/em\u003e in New Zealand. \u003cem\u003eInt J of Infect Dis\u003c/em\u003e 2021; 103: 176\u0026ndash;81.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Oliver J, Thielemans E, McMinn A, et al. Invasive group A \u003cem\u003eStreptococcus\u003c/em\u003e disease in Australian children: 2016 to 2018 \u0026ndash; a descriptive cohort study. \u003cem\u003eBMC Public Health\u003c/em\u003e 2019; doi: 10.1186/s12889-019-8085-2.\u003c/p\u003e\n\u003cp\u003e4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Brusco NK, Oliver J, McMinn A, Steer A, Crawford N. The cost of care for children hospitalised with invasive group A streptococcal disease in Australia. \u003cem\u003eBMC Health Serv Res\u003c/em\u003e 2021; doi: 10.1186/s12913-021-07265-8.\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Wright CM, Moorin R, Pearson G, et al. Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people. \u003cem\u003eMed J Aust\u003c/em\u003e 2021; 215: 36\u0026ndash;41.\u003c/p\u003e\n\u003cp\u003e6.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Dunne E, Hutton S, Peterson E, et al. Increasing incidence of invasive group A \u003cem\u003eStreptococcus\u003c/em\u003e disease, Idaho, USA, 2008\u0026ndash;2019. \u003cem\u003eEmerg Infect Dis\u003c/em\u003e 2022; 28:1785\u0026ndash;95.\u003c/p\u003e\n\u003cp\u003e7.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Tyrrell G, Bell C, Bill L, Fathima S. Increasing incidence of invasive group A \u003cem\u003eStreptococcus\u003c/em\u003e disease in First Nations population, Alberta, Canada, 2003\u0026ndash;2017. \u003cem\u003eEmerg Infect Dis\u003c/em\u003e 2021;27: 443\u0026ndash;51.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Abo YN, Oliver J, McMinn A, et al. Increase in invasive group A streptococcal disease among Australian children coinciding with northern hemisphere surges. \u003cem\u003eLancet Reg Health West Pac\u003c/em\u003e 2023; doi: 10.1016/j.lanwpc.2023.100873.\u003c/p\u003e\n\u003cp\u003e9.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Tomidis Chatzimanouil MK, R\u0026ouml;\u0026szlig;ler S, Nurjadi D, et al. Post-COVID-19-pandemic changes and clinical characteristics of invasive group a streptococcal infections from 2015 to 2023. \u003cem\u003eInfection\u003c/em\u003e 2024; doi: 10.1007/s15010-024-02413-8.\u003c/p\u003e\n\u003cp\u003e10.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Birrell JM, Boyd R, Currie BJ, et al. Invasive group A streptococcal disease in the Northern Territory and the impact of melioidosis antibiotic prophylaxis. \u003cem\u003eMed J Aust\u003c/em\u003e 2022; 217: 544\u0026ndash;5.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e11.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Valenciano SJ, Onukwube J, Spiller MW, et al. Invasive group A streptococcal infections among people who inject drugs and people experiencing homelessness in the United States, 2010\u0026ndash;2017\u003cem\u003e. Clin Infect Dis 2021\u003c/em\u003e; 73: e3718\u0026ndash;26.\u003c/p\u003e\n\u003cp\u003e12.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Goldsmith JJ, Vu C, Zhu Z, MacLachlan JH, et al. The associations between invasive group A streptococcal disease and infection with influenza, varicella, or hepatitis C viruses: A data linkage study, Victoria, Australia. \u003cem\u003eInt J Infect Dis\u003c/em\u003e 2024; doi: 10.1016/j.ijid.2024.02.012.\u003c/p\u003e\n\u003cp\u003e13.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Vilhonen J, Vuopio J, Vahlberg T, el al. Group A streptococcal bacteremias in southwest Finland 2007\u0026ndash;2018: epidemiology and role of infectious diseases consultation in antibiotic treatment selection. \u003cem\u003eEur J Clin Microbiol Infect Dis\u003c/em\u003e 2020; 39: 1339\u0026ndash;48.\u003c/p\u003e\n\u003cp\u003e14.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Orieux A, Prevel R, Dumery M, et al. Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study). \u003cem\u003eCrit Care\u003c/em\u003e 2024; doi: 10.1186/s13054-023-04774-2.\u003c/p\u003e\n\u003cp\u003e15.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Couture-Cossette A, Carignan A, Mercier A, et al. Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016. \u003cem\u003ePLoS One\u003c/em\u003e 2018; doi: 10.1371/journal.pone.0206289\u003c/p\u003e\n\u003cp\u003e16.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Mehta S, McGeer A, Low DE, et al. Morbidity and mortality of patients with invasive group A streptococcal infections admitted to the ICU. \u003cem\u003eChest\u003c/em\u003e 2006; 130: 1679\u0026ndash;86.\u003c/p\u003e\n\u003cp\u003e17.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Therapeutic Guidelines. Antibiotic. Melbourne, 2019. \u003cem\u003ehttps://www.tg.org.au\u003c/em\u003e (viewed 2024 Oct 2024).\u003c/p\u003e\n\u003cp\u003e18.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)\u0026mdash;A metadata-driven methodology and workflow process for providing translational research informatics support.\u003cem\u003e\u0026nbsp;J Biomed Inform\u003c/em\u003e 2009; 42(2):377\u0026ndash;81.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e19.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: building an international community of software platform partners. \u003cem\u003eJ Biomed Inform\u003c/em\u003e 2019; doi: 10.1016/j.jbi.2019.103208.\u003c/p\u003e\n\u003cp\u003e20. Morris JM, Lacey JA, Stevens K, et al. Genomic interrogation of invasive group A \u003cem\u003eStreptococcus\u003c/em\u003e (iGAS) epidemiology and COVID-19 impacts in Victoria, Australia: a 6-year retrospective study. Lancet Reg Health West Pac 2025;\u0026nbsp;\u003ca href=\"https://doi.org\"\u003edoi\u003c/a\u003e: 10.1016/j.lanwpc.2025.101467.\u003c/p\u003e\n\u003cp\u003e21. \u0026nbsp; \u0026nbsp; \u0026nbsp;Centre for Communicable Diseases and Prevention. Streptococcal Toxic Shock Syndrome (STSS) (\u003cem\u003eStreptococcus pyogenes\u003c/em\u003e) 2010 case definition, 2016. \u003cem\u003ehttps://ndc.services.cdc.gov/case-definitions/streptococcal-toxic-shock-syndrome-2010/\u003c/em\u003e (viewed Oct 2024).\u003c/p\u003e\n\u003cp\u003e22.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Reserve Bank of Australia. Inflation calculator, 2024. \u003cem\u003ehttps://www.rba.gov.au/calculator\u003c/em\u003e (viewed Sep 2024).\u003c/p\u003e\n\u003cp\u003e23.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Australian Government Department of Health and Aged Care. National communicable diseases surveillance dashboard, 2024. \u003cem\u003ehttps://nindss.health.gov.au/pbi-dashboard\u003c/em\u003e (viewed Sep 2024).\u003c/p\u003e\n\u003cp\u003e24.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Government of Western Australia Department of Health. Notifiable infectious disease dashboard, 2024. \u003cem\u003ehttps://www.health.wa.gov.au/Articles/N_R/Notifiable-infectious-disease-dashboard\u003c/em\u003e (viewed Oct 2024).\u003c/p\u003e\n\u003cp\u003e25.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Australian Government Department of Health and Aged Care. Modified Monash Model. 2023.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e26.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Ong KS, Kelaher M, Anderson I, Carter R. A cost-based equity weight for use in the economic evaluation of primary health care interventions: case study of the Australian Indigenous population. \u003cem\u003eInt J Equity Health\u003c/em\u003e 2009; doi: 10.1186/1475-9276-8-34.\u003c/p\u003e\n\u003cp\u003e27.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Husereau D, Drummond M, Augustovski F, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 explanation and elaboration: a report of the ISPOR CHEERS II Good Practices Task Force. \u003cem\u003eValue Health\u003c/em\u003e 2022; 25: 10\u0026ndash;31.\u003c/p\u003e\n\u003cp\u003e28.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Australian Bureau of Statistics. Estimates of Aboriginal and Torres Strait Islander Australians. Canberra; 2021. \u003cem\u003ehttps://www.abs.gov.au/statistics/people/aboriginal-and-torres-strait-islander-peoples/estimates-aboriginal-and-torres-strait-islander-australians/latest-release\u003c/em\u003e (viewed Nov 2024).\u003c/p\u003e\n\u003cp\u003e29.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Babiker A, Li X, Lai YL, Strich JR, et al. Effectiveness of adjunctive clindamycin in \u0026beta;-lactam antibiotic-treated patients with invasive \u0026beta;-haemolytic streptococcal infections in US hospitals: a retrospective multicentre cohort study. \u003cem\u003eLancet Infect Dis\u003c/em\u003e 2021; 21: 697\u0026ndash;710.\u003c/p\u003e\n\u003cp\u003e30.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Heil EL, Kaur H, Atalla A, et al. Comparison of adjuvant clindamycin vs linezolid for severe invasive group A \u003cem\u003eStreptococcus\u003c/em\u003e skin and soft tissue infections. \u003cem\u003eOpen Forum Infect Dis\u003c/em\u003e 2023; doi: 10.1093/ofid/ofad588\u003c/p\u003e\n\u003cp\u003e31.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Siljander T, Lyytik\u0026auml;inen O, V\u0026auml;h\u0026auml;kuopus S, et al. Epidemiology, outcome and emm types of invasive group A streptococcal infections in Finland.\u003cem\u003e\u0026nbsp;Eur J Clin Microbiol Infect Dis\u003c/em\u003e 2010; 29: 1229\u0026ndash;35.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCFR \u0026ndash; case fatality rate\u003c/p\u003e\n\u003cp\u003eCI \u0026ndash; confidence interval\u003c/p\u003e\n\u003cp\u003eCPI \u0026ndash; cost price index\u003c/p\u003e\n\u003cp\u003eICU \u0026ndash; intensive care unit\u003c/p\u003e\n\u003cp\u003eiGAS \u0026ndash; invasive group A streptococcal\u003c/p\u003e\n\u003cp\u003eIVIg \u0026ndash; intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eIQR \u0026ndash; interquartile range\u003c/p\u003e\n\u003cp\u003ePWID \u0026ndash; people who inject drugs\u003c/p\u003e\n\u003cp\u003eRMH \u0026ndash; Royal Melbourne Hospital\u003c/p\u003e\n\u003cp\u003eSD \u0026ndash; standard deviation\u003c/p\u003e\n\u003cp\u003eSTSS \u0026ndash; streptococcal toxic shock syndrome\u003c/p\u003e\n\u003cp\u003eWGS \u0026ndash; whole genome sequencing\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Demographic and clinical characteristics of adults (\u0026ge;18 years) with iGAS by ICU admission, RMH 2018\u0026ndash;2023\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"106%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 79\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-ICU admissions\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 50\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU admissions\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN = 29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003ein years, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e47 (36,65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e46 (33,68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e47 (39,63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026gt;0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e31 (39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e11 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e48 (61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e30 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e18 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eIntravenous drug use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e11 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eManifestations\u003c/strong\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eBacteraemia with or without focus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e60 (76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e36 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e24 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eNon-necrotizing soft tissue infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e31 (39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e28 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eOsteomyelitis or septic arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e17 (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003ePneumonia or empyema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eNecrotizing soft tissue infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eStreptococcal toxic shock syndrome (STSS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e10 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e10 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome of index hospital admission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eRecovered\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e45 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e35 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e10 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eDeficit\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e20 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12 (24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eDisability\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e7 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eDeceased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e7 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e7 (24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic therapies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eNumber of antibiotics (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4 (3, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4 (3, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5 (4, 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eVancomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e57 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e31 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e26 (90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eCeftriaxone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e52 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e28 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e24 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eClindamycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e52 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e28 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e24 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eMeropenem or piperacillin-tazobactam\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e44 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e24 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eAmoxicillin or amoxicillin-clavulanate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e42 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e33 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9 (31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eBenzylpenicillin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e41 (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e25 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e16 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjunctive therapies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eSurgical intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e45 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e27 (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e18 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eSteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e24 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9 (18%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e15 (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eIntravenous immunoglobulin (IVIg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e11 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eInotropes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e23 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eVasopressors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e13 (45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 41px;\"\u003e\n \u003cp\u003eIntubation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e16 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003en(%) \u003csup\u003eb\u003c/sup\u003eCases may have more than one manifestation. Eight cases had bacteraemia without focus. \u003csup\u003ec\u003c/sup\u003eDeficit is defined as a physical impairment anticipated to improve post-discharge while disability is defined as a permanent physical impairment. \u003csup\u003ed\u003c/sup\u003eWilcoxon rank sum test; Pearson\u0026rsquo;s Chi-squared test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2: Resource unit definition, number of cases whose treatment accrued costs against a resource category, cost per case and total cost for each resource in 2023 AUD\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResource category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnit definition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of cases that accrued costs\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026para; n(%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthcare costs\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal costs across all cases\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n=79)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cem\u003ePer cases exposed to care element costs\u003c/em\u003e\u003csup\u003e\u0026para;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cem\u003ePer case\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n=79)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eED Admission\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eED costs preceding index admission\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e73\u003csup\u003e\u0026sect;\u0026nbsp;\u003c/sup\u003e(92%)\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,359 ($947)\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,359 ($947)\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e$99,187 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex Admission\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eAll costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e79 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$51,056 ($77,732)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$51,056 ($77,732)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e$4,033,444\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eAcute ward admission\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eAcute ward admission, includes medical and nursing utilisation.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e65 (98%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$17,052 ($21,363)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$16,793 ($21,301) \u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCCU admission\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eCCU costs associated with index admission\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1 (2%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$9,984 (N/A)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$151 ($1229)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eICU admission\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eICU costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e24 (36%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$24,046 ($23,178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$8,744 ($18,054)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eHITH admission\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eHITH costs associated with index admission\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e9 (14%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$6,793 ($4017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$926 ($2,739)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eAllied health utilisation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eAllied health costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e65 (98%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,144 ($2042)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,127 ($2,031)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eImaging utilisation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eImaging costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e44 (67%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,136 ($1,021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$758 ($990)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003ePathology utilisation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003ePathology costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e64 (97%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$2,070 ($2,448)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$2,007 ($2,436)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003ePharmacy utilisation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003ePharmacy costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e66 (100%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,551 ($1635)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,551 ($1,635)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTheatre utilisation\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eTheatre and surgery costs associated with index admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e36 (55%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$11,452 ($14,046)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$6,246 ($11,800)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eOther\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eAny other index admission costs not previously specified.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e65 (98%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$5,771 ($6,981)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$5,684 ($6,963)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHospital utilisation within 6 months of index admission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eAny costs incurred at index hospital within 6 months of index admission.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e56 (71%) \u0026Ograve;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$16,012 ($41,443)\u003csup\u003e\u0026Agrave;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$11,350 ($35,562)\u003csup\u003e\u0026Ograve;\u003c/sup\u003e\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e$896,675 \u0026Ograve;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eRe-admissions to the index hospital\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eIncludes all costs associated with emergency and inpatient (acute and subacute) admissions\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e33 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$24,778 ($51,643)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$10,624 ($35,293)\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eOutpatient services\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eIncludes all costs associated with outpatient care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e43 (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$1,333 ($2,061)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$726 ($1,654)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal healthcare utilisation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003eCombines cost of ED admission, index admission and 6 month follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e79 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$63,662 ($84,743)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e$63,662 ($84,743)\u003csup\u003e\u0026nbsp;\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e$5,029,305\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026para;\u0026nbsp;\u003c/sup\u003eCases data presented for cases with costs/healthcare utilisation for each resource category. \u003csup\u003e\u0026Dagger;\u003c/sup\u003e Modelled data for costs n=13 of total sample, therefore total cases n=66 with cost data provided. \u0026nbsp;\u003csup\u003e\u0026fnof;\u003c/sup\u003eThe average cost dropped to $53,866 (SD $54,379) when cases with a LoS \u0026gt;120 days during either their index admission or the 6-month follow-up period were excluded. Cost distribution by resource category did not change.\u003csup\u003e\u0026sect;\u003c/sup\u003e Missing data n=6 \u003csup\u003e\u0026Ograve;\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eModelled data for costs within 6 months n=14, CCU: Coronary care unit; ICU: Intensive care unit; HITH: Hospital in the home\u003c/p\u003e\n\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003eTable 3: \u0026nbsp;Overall healthcare utilisation and cost per subgroup and resource unit in 2023 AUD, mean (SD) \u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eED utilisation costs\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex admission length-of-stay\u0026nbsp;\u003c/strong\u003e(days)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex admission costs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHospital costs within 6 months\u003c/strong\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal healthcare costs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease Outcome\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eFatal\u003c/em\u003e\u003csup\u003e\u0026para; \u0026nbsp;\u003c/sup\u003e(n= 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1075 ($500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1.71 (1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$13,211 ($14,186)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$0 ($0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$14,286 ($14544)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eSurvived\u0026nbsp;\u003c/em\u003e(n=72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,389 ($980)\u003csup\u003e\u0026ograve;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e16.58 (22.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$54,736 ($80,411)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$12,454 ($37,086)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$68,463 ($87,223)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eRecovered\u003c/em\u003e (n= 46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,628 ($1,016)\u003csup\u003e\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e10.62 (11.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$33,285 ($39,962)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$7,150 ($14,303)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$41,921 ($42,964)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eDeficit\u003c/em\u003e (n= 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,162 ($811)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e26.65 (37.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$82,109 ($124,700)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$25,684 ($66,796)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$108,832 ($130,815)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eDisability\u003c/em\u003e (n= 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$507 ($373)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e28.48 (19.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$121,397 ($82,475)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$11,400 ($24,178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$133,303 ($96,843)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003e18-39 years\u003c/em\u003e (n=21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,510 ($953)\u0026circ;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12.12 (10.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$45,821 ($53,439)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$5,841 ($18,948)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$53,099 ($55,672)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003e40-59 years\u0026nbsp;\u003c/em\u003e(n=33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,192 ($867)\u003csup\u003e\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20.61 (32.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$69,602 ($108,267)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$8,559 ($17,627)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$79,208 ($111,605)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003e60-79 years\u0026nbsp;\u003c/em\u003e(n=10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,150 ($725)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14.95 (8.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$46,108 ($31,309)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$38,281 ($88,499)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$85,539 ($80,825)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003e80 years and over\u0026nbsp;\u003c/em\u003e(n=8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$2,202 ($1,459)\u0026circ;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e13.75 (6.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$27,600 ($18,737)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$13,596 ($16,648)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$43,123 ($23,825)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e (n= 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,708 ($973)\u003csup\u003e\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e13.11 (9.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$36,041 ($23,597)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$13,721 ($53,270)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$51,234 ($52,155)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e (n= 43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,194 ($943)\u003csup\u003e\u0026Dagger; \u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e18.93 (28.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$67,344 ($100,773)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$11,599 ($20,771)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$80,082 ($103,461)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;ICU admission\u0026nbsp;\u003c/em\u003e(n=21)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,126 ($840)\u003csup\u003e\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e19.68 (17.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$89,864 ($67,017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$8,596 ($17,629)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$99,426 ($73,790)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eNon-ICU admission\u003c/em\u003e (n= 50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,487 ($1,018)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e15.18 (25.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$39,803 ($82,328)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$14,318 ($43,048)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$55,548 ($90,663)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery related to illness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e (n= 46)\u003csup\u003e\u0026Agrave;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,080 ($737)\u003csup\u003e\u0026nbsp;\u0026fnof;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20.78 (27.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$69,122 ($94,556)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$10,166 ($20,233)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$80,274 ($97,365)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e (n= 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e$1,929 ($1,125)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9.15 (6.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$29,283 ($34,860)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e$16,502 ($56,058)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e$47,566 ($61,901)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 139px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eHospital costs within 6 months of discharge from index admission, including re-admissions to the index hospital (emergency department, acute and subacute) and outpatient services.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026para;\u0026nbsp;\u003c/sup\u003eDeath occurred during index admission. Cases that died during the index admission were excluded from the sub-group analysis of age, gender, disease severity and surgery related to illness.\u0026nbsp;\u003csup\u003e\u0026ograve;\u003c/sup\u003e Missing data n=6. \u0026nbsp;\u003csup\u003e\u0026fnof;\u0026nbsp;\u003c/sup\u003eMissing data n= 4. \u003csup\u003e\u0026Dagger; \u0026nbsp;\u003c/sup\u003eMissing data n= 2.\u0026nbsp;\u0026circ;Missing data n=1\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026Agrave;\u003c/sup\u003e n=2 cases had procedures at bedside that were included as \u0026lsquo;surgery\u0026rsquo;, theatre resource costs were not allocated as they were included as part of the acute ward admission costs.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u003c/sup\u003e n=1 case was excluded from this sub-group analysis. This case had a disrupted admission at the index hospital and was transferred to a different hospital during the episode of care at the index hospital. The significant portion of the index admission was the second part of the admission to the index hospital, this data is what was used for the economic evaluation of the study.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"invasive group A streptococcal disease, cost burden study","lastPublishedDoi":"10.21203/rs.3.rs-5847008/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5847008/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eObjectives: To describe the epidemiology, clinical course, genomics, and cost burden of hospital care of invasive group A streptococcal (iGAS) amongst adults (≥18 years) treated at the Royal Melbourne Hospital (RMH) during 2018-2023 and extrapolate findings to estimate the annual healthcare cost burden of treating adult iGAS cases in Australia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethods: Retrospective cohort study and economic evaluation, including a single hospital cost burden analysis followed by a national cost extrapolation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults: There were 79 eligible iGAS cases between 2018-2023. Seven cases were fatal (case fatality rate: 9%, 95% CI: 4%–18%), one third (29, 35%) were admitted to intensive care and one third (27; 38%) of non-fatal cases were discharged with an impairment. The average iGAS disease-related healthcare cost was $63,662 (SD $84,743) per person, with a combined healthcare utilisation cost for the cohort of $5,029,305. Most costs (80%) were incurred during the index admission. In 2023, the estimated national healthcare cost burden for adults with iGAS was $117.5 million.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConclusions: iGAS among adults in Australia generates a significant health and financial burden. Our findings highlight the importance of investment in research to prevent iGAS and identify the optimal treatment for this severe infection.\u003c/p\u003e","manuscriptTitle":"Invasive group A streptococcal infections in Australian adults – a descriptive cohort and cost burden study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-05 17:36:15","doi":"10.21203/rs.3.rs-5847008/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"69271305965189195418355925769013414951","date":"2025-03-17T10:35:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-03T11:19:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-26T04:46:05+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-02-04T09:23:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-31T02:01:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2025-01-31T02:00:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"82713baf-2b93-42d7-992b-9d3f258d3074","owner":[],"postedDate":"March 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-03-05T17:36:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-05 17:36:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5847008","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5847008","identity":"rs-5847008","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}