Patient-Reported Outcomes Following Periprosthetic Joint Infection of the Hip and Knee: A Longitudinal, Prospective Observational Study.

BACKGROUND: The role of patient-reported outcome measures (PROMs) as tools for monitoring the impact and outcomes of periprosthetic joint infection (PJI) is not well described. This study analyzed the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) in a prospective observational cohort of patients with hip or knee PJI. METHODS: The PIANO (Prosthetic joint Infection in Australia and New Zealand, Observational study) cohort prospectively enrolled patients with newly diagnosed PJI from multiple centers. The OHS and OKS were evaluated at PJI diagnosis (baseline) and at 3, 12, and 24 months. Scores and score changes were examined according to PJI type, patient characteristics, and management. A successful functional outcome at 12 months was defined as an OHS of >38 or OHS of >36 and/or an improvement from baseline of >12 or >9, respectively. RESULTS: Of the 741 participants, PROMs were available at 12 months for 233 with hip and 342 with knee PJI. Significant improvements (p < 0.0001) were seen at 12 months for both the OHS (24.5 to 36) and OKS (25 to 34), with no further improvement at 24 months. Patients with late-acute PJI had a higher median baseline OHS (35; interquartile range [22 to 46]) and OKS (30 [18 to 41]) than those with early PJI (OHS: 19 [15 to 29]; OKS: 22 [16 to 29.5]) or chronic PJI (OHS: 23 [14 to 34]; OKS 22 [14 to 28]). Logistic regression showed that a clinical cure (adjusted odds ratio [aOR] = 1.88, 95% confidence interval [CI] = 1.28 to 2.76, p = 0.001) and early PJI (aOR = 2.56, 95% CI = 1.64 to 4.07, p < 0.0001) independently predicted a successful functional outcome. Chronic renal impairment (aOR = 0.31, 95% CI = 0.13 to 0.71, p = 0.007), congestive cardiac failure (aOR = 0.41, 95% CI = 0.17 to 0.95, p = 0.04), and clinical signs of inflammation (aOR = 0.53, 95% CI = 0.33 to 0.85, p = 0.009) at diagnosis independently predicted failure to achieve a successful functional outcome. CONCLUSIONS: The OHS and OKS varied significantly at baseline and 12 months according to PJI type, emphasizing the need to consider the PJI type when evaluating treatment success. This study highlights superior functional outcomes associated with early PJI and with achievement of a clinical cure. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prevalence, risk factors, and outcomes of secondary infections among hospitalized patients with COVID-19 or post-COVID-19 conditions in Victoria, 2020-2023.

OBJECTIVES: Estimates of secondary infections are variedly reported, with few studies done in Australia. We investigated the occurrence and impact of secondary infections complicating COVID-19 and post-COVID-19 admissions in Victoria, Australia, 2020-2023. METHODS: We used linked population-wide data sets and specific International Classification of Disease, 10th Revision codes to identify and estimate the occurrence of secondary infections. Using hospital/intensive care unit length of stay in negative binomial regression and mortality, we examined the impact of secondary infections. RESULTS: Secondary infections were identified in 6.9% (13,467 of 194,660) of COVID-19 and post-COVID-19 admissions: 6.0% (11,651 of 194,660) bacterial, 0.9% (1691 of 194,660) viral, and 0.2% (385 of 194,660) fungal. Prevalence was highest during the pre-Delta (10.4%) and Omicron-BA2 (8.1%) periods. Sepsis and pneumonia were the most reported syndromes; the occurrence of sepsis declined gradually over time. The odds of secondary infections were higher among the ≥70-year-olds (adjusted odds ratio (aOR) 3.76, 95% confidence interval [CI] 3.43-4.14, vs 20-29-year-olds), individuals with chronic conditions (aOR 3.15, 95% CI 2.88-3.45, vs those without), the unvaccinated (aOR 1.59, 95% CI 1.45-1.75), and the lowest socioeconomic group (aOR 1.12, 95% CI 1.05-1.19). Patients with secondary infections had 2.43 times longer hospital length of stay and 9.60 times longer intensive care unit length of stay than those without secondary infections. The mortality risk was 2.17 times higher in those with secondary infections. CONCLUSIONS: Secondary infections occurred in 69 per 1000 COVID-19-associated hospital admissions in Victoria, mostly in high-risk groups, and were associated with severe outcomes.

Efficacy and safety of respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over 2 RSV seasons.

BACKGROUND: The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-year-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1. METHODS: In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided confidence intervals [CIs] around efficacy estimates >20%). RESULTS: The efficacy analysis comprised 24,967 participants (RSV_1dose: 6227, RSV_revaccination: 6242, placebo: 12,498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. CONCLUSION: One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. ClinicalTrials.gov registration: NCT04886596.

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

Use of targeted SMS messaging to encourage COVID-19 oral antiviral uptake in South West Victoria.

OBJECTIVES: During winter 2022, as part of a multifaceted approach to optimise oral antiviral uptake in the Barwon South West region in Victoria, Australia, the Barwon South West Public Health Unit (BSWPHU) implemented an innovative, targeted SMS messaging program that encouraged people with coronavirus disease 2019 (COVID-19) to be assessed for antiviral treatment. In this study, we investigated patterns of antiviral uptake, identified barriers and facilitators to accessing antivirals, and examined the potential impact of targeted SMS messaging on oral antiviral uptake. METHODS: We conducted a cross-sectional study of notified COVID-19 cases aged 50 years and older, and Aboriginal and Torres Strait Islander people aged 30-49 years, in the BSWPHU catchment area over a 6-week period commencing 21 July 2022. We analysed survey data using descriptive statistics and generalised linear models. RESULTS: Of the 3829 survey respondents, 36.7% (95% confidence interval (CI) 35.2, 38.2) reported being prescribed oral antivirals, with 75.4% (95% CI 72.8, 77.9) of these aged ≥70. Antiviral prescriptions increased significantly over the 6-week survey period. Most prescriptions (87.5%; 95% CI 85.7, 89.2) were provided by the respondents' usual general practitioners (GPs). Barriers to receiving antivirals included respondents being unable to get a medical appointment in time (3.7%; 95% CI 3.1, 4.2), testing too late in their illness (2.3%; 95% CI 1.8, 2.8) and being unable to access medications in time after receiving a prescription (0.2%; 95% CI 0.1, 0.6). Facilitators to receiving antivirals included respondents first hearing about antivirals from a trusted source such as a family member, friend or usual doctor. Nearly one in eight people who were prescribed antivirals reported first hearing about them from the SMS message sent by BSWPHU. CONCLUSIONS: Oral antiviral treatment uptake in south-west Victoria in July-August 2022 was high among survey respondents and increased over time. GPs were the key prescribers in the community. Targeted SMS messaging to COVID-19 cases is a simple, low-cost intervention that potentially increases antiviral uptake.

A serological assay using Tropheryma whipplei antigens for the presumptive exclusion of Whipple disease.

Whipple disease (WD) is a rare infection in genetically susceptible people caused by the bacterium Tropheryma whipplei. An indirect immunofluorescence serological assay (IFA), detecting patient antibodies to the bacterium, was developed using T. whipplei as antigen. We hypothesised that this assay could be used to rule out WD in patients in whom the diagnosis was being considered, based on high immunoglobulin (Ig) G titres to T. whipplei. In this study, 16 confirmed WD patients and 156 age-matched controls from across Australia were compared serologically. WD patients mostly underproduced IgG antibody to T. whipplei, with titres of ≤1:32 being common. While at an antibody titre of <1:64 the assay sensitivity for WD was only 69% [95% confidence interval (CI) 41-89%], its specificity for excluding WD was 91% (95% CI 85-95%). This specificity increased to 95% (95% CI 90-98%) at an antibody titre of <1:16. Patients with antibody titres of >1:64 were unlikely to have WD. At this titre, the seroprevalence of T. whipplei IgG antibody was 92% (223/242) in Australian blood donors. Unlike other serological assays, which are used to confirm a specific infection, this novel assay is designed to rule out WD infection with a specificity in Australia of 91%. Further validation of this assay, by trialling in other countries, should now be undertaken, as its usefulness is dependent on there being a high background seropositivity to T. whipplei in the general population at the location in which the assay is being used.

Pseudomonas aeruginosa: Infections and novel approaches to treatment "Knowing the enemy" the threat of Pseudomonas aeruginosa and exploring novel approaches to treatment.

Pseudomonas aeruginosa is an aerobic Gram-negative rod-shaped bacterium with a comparatively large genome and an impressive genetic capability allowing it to grow in a variety of environments and tolerate a wide range of physical conditions. This biological flexibility enables the P. aeruginosa to cause a broad range of infections in patients with serious underlying medical conditions, and to be a principal cause of health care associated infection worldwide. The clinical manifestations of P. aeruginosa include mostly health care associated infections and community-acquired infections. P. aeruginosa possesses an array of virulence factors that counteract host defence mechanisms. It can directly damage host tissue while utilizing high levels of intrinsic and acquired antimicrobial resistance mechanisms to counter most classes of antibiotics. P. aeruginosa co-regulates multiple resistance mechanisms by perpetually moving targets poses a significant therapeutic challenge. Thus, there is an urgent need for novel approaches in the development of anti-Pseudomonas agents. Here we review the principal infections caused by P. aeruginosa and we discuss novel therapeutic options to tackle antibiotic resistance and treatment of P. aeruginosa infections that may be further developed for clinical practice.

Demographic Characteristics of Unvaccinated Asymptomatic and Symptomatic SARS-CoV-2 Cases in Barwon South West, Victoria, Australia.

We investigated 328 SARS-CoV-2 cases in Barwon South West, Victoria, Australia, in the 2020 pre-vaccination period, comparing infections with symptoms to those that remained asymptomatic. De-identified self-reported data on case characteristics and symptom progression from three sequential questionnaires were examined. Multivariable logistic regression was used to model associations between demographic profiles and symptoms. Asymptomatic infections were more than three times as likely to be seen in ethnic minority groups than the Caucasian population after adjusting for gender and age [OR 3.2, 95% CI 1.5-6.7, p < 0.01] and were more common among cases of Asian background [OR 2.8, 95%CI 1.2-6.4]. Asymptomatic infections were also more common in youth and younger adults, but cases were approximately seven times more likely to be in seniors (≥65 years) compared with those 24 years of age or younger after adjusting for sex and ethnicity [OR 6.9, 95% CI 1.3-35.8]. The overrepresentation of ethnic minority groups among asymptomatic infections is suggestive of genetic haplotype variability by ethnic group, conferring greater cross-protection from other coronaviruses in the initial phase of the COVID-19 pandemic. Replication of this analysis in the post-vaccination era and reassessment of symptom expression according to ethnicity in a community with established vaccine and infection-induced immunity would determine whether this is a sustained association or one confined to the early stages of a pandemic in an immunologically naive population. These findings may, in part, reflect differences in testing patterns by ethnicity and true differences in disease expression, both of which are important to understand in order to inform transmission prevention strategies and tailored risk messaging according to ethnic background.

Outreach nurses critical for delivery of HIV care to women in western Victoria.

Women living with HIV in regional Victoria face barriers accessing care. We evaluated the care cascade and outreach nurse support required for women attending our service between 2005 and 2020. A total of 33 women attended; 97% (32/33) were on antiretroviral therapy; 67% (22/33) retained in care, 27% (9/33) transferred and 6% (2/33) lost to follow up. Of women retained in care, 95% (21/22) were on antiretroviral therapy and 91% (20/22) had virological suppression. A total of 91% (30/33) required outreach nurse care (median care episodes 100/woman; IQR 44-179) - most frequently (87%; 26/30) liaising with pharmacies and prescribers. Outreach nurses are critical in achieving UNAIDS targets for women in western Victoria.

Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. METHODS: The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy ≥65-year-olds in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein-based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% CI >0.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. RESULTS: Of 1403 participants randomized, 1399 received vaccinations (median [range] age, 70 [65‒91] years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin. CONCLUSION: The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older adult population. CLINICAL TRIAL REGISTRATION: NCT05301322.

Comprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, polymerase chain reaction, amplicon/metagenomic sequencing, in situ hybridization), imaging (positron emission computed tomography with 18F-fluorodeoxyglucose, cardiac computed tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of "typical" microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the Duke-ISCVID Criteria available online as a "Living Document."

Mycobacterium ulcerans culture results according to duration of prior antibiotic treatment: A cohort study.

Mycobacterium ulcerans disease is a necrotising disease of the skin and subcutaneous tissue and is effectively treated with eight-weeks antibiotic therapy. Significant toxicities, however, are experienced under this prolonged regimen. Here, we investigated the length of antibiotic duration required to achieve negative cultures of M. ulcerans disease lesions and evaluated the influence of patient characteristics on this outcome. M. ulcerans cases from an observational cohort that underwent antibiotic treatment prior to surgery and had post-excision culture assessment at Barwon Health, Victoria, from May 25 1998 to June 30 2019, were included. Antibiotic duration before surgery was grouped as <2 weeks, ≥2-<4 weeks, ≥4-<6 weeks, ≥6-<8 weeks, ≥8-<10 weeks and ≥10-20 weeks. Cox regression analyses were performed to assess the association between variables and culture positive results. Ninety-two patients fitted the inclusion criteria. The median age was 60 years (IQR 28-74.5) and 51 (55.4%) were male. Rifampicin-based regimens were predominantly used in combination with clarithromycin (47.8%) and ciprofloxacin (46.7%), and the median duration of antibiotic treatment before surgery was 23 days (IQR, 8.0-45.5). There were no culture positive results after 19 days of antibiotic treatment and there was a significant association between antibiotic duration before surgery and a culture positive outcome (p<0.001). The World Health Organisation category of the lesion and the antibiotic regimen used had no association with the culture outcome. Antibiotics appear to be effective at achieving negative cultures of M. ulcerans disease lesions in less than the currently recommended eight-week duration.

Insights into the Evolution of P. aeruginosa Antimicrobial Resistance in a Patient Undergoing Intensive Therapy.

Whole genome sequencing (WGS) provides insights into the evolution of antimicrobial resistance, an urgent global health threat. Using WGS, we observe evolutionary adaptation of a Pseudomonas aeruginosa strain within an immunocompromised patient undergoing antibiotic therapy. Two blood isolates (EA-86 and EA-87) from the patient evolved separate adaptations for antibiotic resistance, while sharing common adaptive mutations for host immune evasion. In EA-86, a silencing mutation in the antibiotic efflux pump repressor, NfxB, increased antibiotic resistance, while in EA-87, a similar mutation was seen in the antibiotic efflux pump repressor mexR. The number of genomic variants between the two isolates give a divergence time estimate of the order of 1000 generations. This time is sufficient for a bacterial lineage to have evolved an SNP in every position in the genome and been fixed if advantageous. This demonstrates the evolutionary adaptive power accessible to bacteria and the timescale for a brute-force functional survey of the SNP fitness landscape.

Is Education Alone Enough to Sustain Improvements of Antimicrobial Stewardship in General Practice in Australia? Results of an Intervention Follow-Up Study.

Sustained behaviour change and practice improvements for the optimal use of antimicrobials remains challenging in primary care. In 2018, a simple antimicrobial stewardship education programme involving guideline recommendations for common infections, antimicrobial audit reports, and local antibiograms resulted in significant improvements in guideline compliance and more appropriate antimicrobial prescribing by GPs. This observational follow-up study aims to examine the sustainability of the positive intervention effect after two years of implementation of the intervention. Practice-based data on all oral antimicrobial prescriptions issued by GPs were collected retrospectively to compare with intervention data and to measure the sustainability of the intervention effect. The data were analysed using a two-sample test of proportions. The primary outcomes included changes in the rate of prescription compliance with the Australian "Therapeutic Guidelines: Antibiotic" and the appropriateness of antimicrobial choice and duration of therapy. Overall, there was a significant decline in guideline compliance, from 58.5 to 36.5% (risk ratio (RR) (95% CI): 0.62 (0.52-0.74)), in the appropriateness of antimicrobial choice, from 92.8 to 72.8% (0.78 (0.73, 0.84)), and in the prescribed duration, from 87.7 to 53.3% (0.61 (0.54, 0.68)) in the intervention follow-up period. In respiratory infections and ear, nose, and throat infections, the rates of guideline compliance and appropriate choice and duration of antimicrobial prescription decreased significantly at p < 0.001. Appropriateness in the duration of antimicrobial therapy also significantly decreased for most antimicrobials. The evidence suggests that a simple and single-occasion antimicrobial stewardship education programme is probably not enough to sustain improvements in the optimal use of antimicrobials by GPs. Future research is needed to validate the results in multiple GP clinics and to examine the effect of sustained education programmes involving infection-specific and antimicrobial-targeted audits and feedback.

Improving diagnostic antimicrobial stewardship in respiratory tract infections: a protocol for a scoping review investigating point-of-care testing programmes in community pharmacy.

INTRODUCTION: Diagnostic uncertainty regarding the cause of respiratory tract infections (RTIs) multiplies the problem of unnecessary use of antibiotics and antimicrobial resistance in primary care. Point-of-care testing (POCT) programmes have been recognised as a potential stewardship strategy to optimise antimicrobial use in primary care. There is a need for greater understanding of community pharmacy-based POCT programmes in reducing the unnecessary use of antimicrobials in patients with RTIs. This review systematically maps out evidence around the effectiveness, feasibility and implementation challenges of POCT programmes in community pharmacy to improve safe antimicrobial use in RTIs. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist and the Arksey and O'Malley methodology framework will guide the reporting of this review. We will systematically review studies with either randomised controlled trial, non-randomised controlled trial, before-after study, observational study or pilot feasibility study design. Medline, Emcare, PubMed, Health Technology Assessment, Cochrane Central Register of Controlled Trials and Google Scholar databases will be used to search for articles. Three reviewers will independently screen, review and select studies with POCT programmes involving community pharmacists for antimicrobial stewardship in RTIs. Summary statistics and random effects model, if data permit, will be used to summarise the effectiveness, feasibility and cost-effectiveness of the POCT programme. The Consolidated Framework for Implementation Research will capture POCT implementation drivers. ETHICS AND DISSEMINATION: This review study does not require research ethics approval. Findings will be disseminated through national and international conferences, seminars and publication in a peer-reviewed journal.

Severity of COVID-19 among Residents in Aged Care Facilities in Victoria, Australia: A Retrospective Cohort Study Comparing the Delta and Omicron Epidemic Periods.

OBJECTIVES: During the COVID-19 pandemic, no country with widespread community transmission has avoided outbreaks or deaths in residential aged care facilities (RACFs). As RACF residents are at high risk of morbidity and mortality from COVID-19, understanding disease severity risk factors is imperative. DESIGN: This retrospective cohort study aimed to compare COVID-19 disease severity (hospitalization and deaths) and associated risk factors among RACF residents in Victoria, Australia, across Delta and Omicron epidemic periods. SETTINGS AND PARTICIPANTS: Resident case hospitalization risk (HR) and case fatality risk (CFR) were assessed using Victorian RACFs COVID-19 outbreaks data across 2 epidemic periods; Delta, 994 resident cases linked to 86 outbreaks; and Omicron, 1882 resident cases linked to 209 outbreaks. METHODS: Adjusting for outbreak-level clustering, age, sex, up-to-date vaccination status, and time since last vaccination, the odds of hospitalization and death were compared using mixed effects logistic regression. RESULTS: The HR and CFR was lower during the Omicron period compared with the Delta period [HR 8.2% vs 24.6%, odds ratio (OR) 0.17, 95% CI 0.11-0.26, and CFR: 11.4% vs 18.7%, OR 0.40, 95% CI 0.28-0.56]. During both periods, males had higher odds of hospitalization and odds of death; being up to date with vaccination reduced odds of hospitalization by 40% (excluding nonemergency patient transfers) and odds of death by 43%; and for each month since last vaccination, odds of hospitalization increased by 9% and odds of death by 16%. CONCLUSIONS AND IMPLICATIONS: This study provides empirical evidence of lower COVID-19 severity among RACF residents in the Omicron period and highlights the importance of up-to-date and timely vaccination to reduce disease severity in this cohort.

Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.