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The changing phenotype of coronarvirus disease 2019 (COVID‐19) may quickly render guideline‐recommended interventions obsolete. We developed a 40‐question clinician survey in consultation with the Australasian COVID‐19 Trial site investigators. The survey was designed to assess clinician perceptions of the current treatment strategies and future research priorities in the management of non‐critically ill patients admitted to hospital with SARS‐CoV‐2 infection. There were 84 complete responses from predominantly Australian and New Zealand clinicians. The perceived prevalence of patients with incidental COVID‐19, nosocomial infection, underlying illness exacerbated by COVID‐19, and/or immunocompromised status suggests new populations to target. The results highlighted clinician interest in antiviral therapies for future research in both immunocompetent and immunocompromised cohorts. These survey results underscore the need for ongoing surveillance of COVID‐19 disease phenotypes and clinician and patient priorities for future research. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases (ID) physicians perform a pivotal role in directing the response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Aim: To assess the impact of SARS‐CoV‐2 on workload and the perceptions of ID physicians regarding the national response in Australia and New Zealand in the pre‐pandemic. Methods: A survey of ID physicians in Australia and New Zealand was undertaken from 3 to 10 March 2020. Respondents were asked to estimate time spent on SARS‐CoV‐2‐related activities in February and report their agreement with statements on a 5‐point Likert scale ranging from 'strongly agree' to 'strongly disagree'. We also asked about the intended use of investigational agents. Results: There were 214 respondents (36% of 600 eligible participants). The median workload due to SARS‐CoV‐2‐related activities was 34% of one full‐time equivalent (interquartile range 18–68%). Less than a quarter (50, 23%) of respondents had experience managing cases, while 33% (70) had experience preparing during similar pandemics. Nevertheless, 88% (188/213) believed they were well informed when giving testing and management advice, and 45% (95/212) believed their national response was well coordinated. Additionally, 41% (88/214) were worried about becoming infected through occupational exposure. Over half (116, 54%) the respondents intended to use lopinavir/ritonavir in confirmed cases of COVID‐19 with severe disease. Conclusions: ID physicians spent a large proportion of time on SARS‐CoV‐2‐related activities. Increased staffing is required to avoid burnout. Importantly, ID physicians feel well informed when giving advice. A national body should be established to co‐ordinate response. Treatment efficacy trials are needed to clarify the utility of unproven treatments. [ABSTRACT FROM AUTHOR]

Aims: COVID-19 is now a global pandemic. At the time of survey, fewer than 150 children in Australia and New Zealand had documented infection. The aim of this study was to assess attitudes, readiness and confidence in the early stages of the COVID-19 pandemic through an online survey of paediatric physicians and sub-specialists across Australia and New Zealand.Methods: Multiple email list groups were used to contact paediatric physicians to undertake an online Likert scale survey between 17 and 24 March. Respondents' specialty, experience and work setting were recorded. Ordinal logistic regression was used to determine respondent factors.Results: There were 542 respondents from across Australia and New Zealand: an estimated 11% of the paediatric physician workforce. A minority (36.6%) agreed that their national response had been well coordinated; the majority (92.7%) agreed that senior-level hospital administrators were taking the situation seriously. Most reported a good understanding of the natural history of COVID-19 in children, and knowledge of where to find local information. A large proportion of physicians (86.1%) were worried about becoming infected through their work; few (5.8%) reported that they would not come to work to avoid infection. Closure of school and childcares would reduce the ability to continue work at current capacity for 23.6% of respondents.Conclusion: Despite limited experience in pandemics, most paediatric physicians felt informed. Concern about exposure at work is common; most were willing to work regardless. The closure of schools and daycares may have an impact on staffing. Coordination and leadership will be critical. [ABSTRACT FROM AUTHOR]

Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection.Trial Design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management.Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently.Intervention and Comparator: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine.Main Outcomes: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated.Randomisation: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform.Blinding (masking): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required.Numbers To Be Randomised (sample Size): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440.Trial Status: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021.Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia.Methods/design: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint.Discussion: Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability.Trial Registration: ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015. [ABSTRACT FROM AUTHOR]

Background: Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking.Methods: An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to β-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed.Discussion: This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT.Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p . Registered on 6 October 2017. [ABSTRACT FROM AUTHOR]

Introduction: Staphylococcus aureus bacteraemia (SAB) is the most common cause of sepsis, contributing to paediatric intensive care unit admission in Australia and New Zealand. While deep venous thrombosis (DVT) has been reported in children with invasive S. aureus infections, the actual frequency and possible effects of thrombosis on disease severity and outcome in paediatric SAB remain unknown. Moreover, guidance regarding imaging for paediatric SAB management are poorly defined., Methods and Analysis: We report the protocol for the SNOOPY (Staphylococcus aureus Network; ultrasOund for diagnOsis of endovascular disease in Paediatrics and Youth) study. SNOOPY is a pilot prospective single-arm interventional study that aims to investigate the proportion of children with SAB that have venous thrombosis detected using whole body doppler ultrasound., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)