Medications for early treatment of COVID-19 in Australia.

Early treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can prevent hospitalisation and death in patients with coronavirus disease 2019 (COVID-19) who have one or more risk factors for serious COVID-19 progression. While early treatment presents a range of logistical challenges, clinicians are nevertheless aided by a growing number of approved medications for early treatment of COVID-19. Medications include drugs that inhibit SARS-CoV-2 viral replication, anti-SARS-CoV-2 monoclonal antibody formulations that provide passive immunisation, and immunomodulatory drugs that suppress the body's inflammatory response. Several drugs with different modes of action are approved in Australia for early treatment of COVID-19, including nirmatrelvir plus ritonavir, molnupiravir, and monoclonal antibody formulations. Although these drugs are recommended, clinicians are encouraged to remain up to date on current indications, contraindications and the clinical efficacy of these drugs against SARS-CoV-2 variants currently circulating in communities. Other treatments, including hydroxychloroquine, ivermectin and dietary supplements, have been popularised but are not recommended for early treatment of COVID-19. As new drugs and new data on use of existing approved drugs become available, clinicians face a growing challenge in determining the optimal treatments from the array of options. As it stands, early treatment of COVID-19 needs to be individualised depending on age, pregnancy status, existing medications, and renal and liver disease status. Future treatments in development might have roles in patients with lower risk profiles and in reducing transmission as we learn to live with SARS-CoV-2.

The first Australian experience with ward-based continuous positive airway pressure for COVID-19 respiratory failure: a retrospective cohort study.

We present the first Australian cohort of patients with COVID-19 respiratory failure managed with escalating respiratory support including continuous positive airway pressure (CPAP) on a standard medical ward at a tertiary Sydney hospital during the 2021 COVID-19 Delta variant outbreak. We demonstrate an equivalent mortality to CPAP delivered in intensive care unit and outline our ward structure and management during the pandemic.

Recent history of psittacosis in Australia: expanding our understanding of the epidemiology of this important globally distributed zoonotic disease.

Psittacosis is a human systemic disease caused by infection with Chlamydia psittaci. Shortly after reports emerged of a global pandemic associated with contact with imported parrots, Australian researchers including Macfarlane Burnet and others demonstrated that C. psittaci was widespread in Australian parrots. Australian cases over the last two decades have revealed that environmental exposure and contact with infected horses are also risk factors in an increasingly complicated epidemiological picture for this zoonotic disease.

Outpatient parenteral antibiotic therapy in a suburban tertiary referral centre in Australia over 10 years.

PURPOSE: Outpatient parenteral antibiotic therapy (OPAT) is a widely accepted and safe therapeutic option for carefully selected patients. This study reviewed the practice of an OPAT service in a large Australian tertiary teaching hospital in Western Sydney over a 10-year period. METHOD: Data were retrieved from a prospectively maintained electronic database which included information on patient demographics, clinical diagnosis, microbiological identity, antimicrobial therapy, complications and readmissions. Data were analysed using descriptive statistics. RESULTS: There were 3435 referrals made to the service between January 2004 and June 2014, amounting to 25,289 antibiotic days. The most frequent referral was for Skin and Soft Tissue Infections (SSTIs), 61.28%, followed by Bone and Joint Infections (BJIs), 15.30%. The most common organism identified was methicillin-sensitive Staphylococcus aureus. Readmission was uncommon (5.15%), with the highest rate of readmission noted for Cardiovascular System Infections (16.67%) followed by BJIs (10.31%). Line infection, aseptic thrombophlebitis and drug hypersensitivity or reaction were the cause of 68.55% of all complications. There was a decline in line-related complications throughout the study period. CONCLUSION: OPAT service is in increasing demand in Australia, providing a significant relief in in-hospital days. Growth in referrals was seen not only with SSTIs and BJIs, but also a diverse range of other infective entities with limited literature in its treatment in an OPAT setting. This study highlights the need to improve data collection, develop risk stratification strategies and standardisation of OPAT services in Australia.

Changes in User Perceptions of a Telemedicine System Over Time: From Initial Implementation to Everyday Use.

BACKGROUND: Benefits associated with telemedicine are contingent upon positive user perceptions. Despite this, research on user perceptions of telemedicine remains limited. INTRODUCTION: Usability approaches offer a robust way to assess user perceptions, but have rarely been applied in telemedicine. In this study, a usability approach was employed to examine how user perceptions toward a telemedicine system changed over the course of everyday use. MATERIALS AND METHODS: A telemedicine system was introduced to a hospital in the home service. Ten mobile nurses completed the System Usability Scale (SUS) after initial use, then again after 18 months of everyday use. Results were compared. Analysis included Bangor et al.'s (2009) adjective rating scale. RESULTS: The initial SUS mean was 83 (standard deviation [SD] = 7.98), indicating "excellent" usability. After 18 months, the SUS mean was 64.38, indicating "OK" usability (SD = 14.25, p < 0.05, 95% confidence interval [CI]). Over time, users had lower desire to use the system frequently (p < 0.05, 95% CI), found it more complex (p < 0.05, 95% CI), and perceived greater inconsistency in its design (p < 0.05, 95% CI). DISCUSSION: Considered with existing evidence, our usability findings indicate that a temporary period of positive user perceptions occurs when new telemedicine systems are used for the first few months. This fades with everyday use, with design inconsistency and perceived complexity becoming more noticeable. Although other factors such as user satisfaction and efficiency may also contribute, further studies are needed for confirmation. CONCLUSIONS: User perceptions of telemedicine vary with time. To help maximize the benefits and longevity of telemedicine systems, responding to intermittent user appraisal is desirable.

Mixed gonococcal infections in a high-risk population, Sydney, Australia 2015: implications for antimicrobial resistance surveillance?

OBJECTIVES: Previous studies have shown that mixed-strain gonococcal infections can occur. However, it remains unclear whether such infections impact upon the reliability of Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance. In this study, we aimed to resolve this question by intensively sampling isolates from gonorrhoea-positive specimens in a high-risk population in Sydney, Australia. METHODS: A total of 615 N. gonorrhoeae isolates, originating from 63 clinical samples (31 rectal swabs and 32 throat swabs), were characterized. All isolates were subject to N. gonorrhoeae identification, antimicrobial susceptibility testing and genotyping by SNP-based MLST. RESULTS: Only 2 of the 63 (3.2%) samples provided evidence of mixed-strain infections. These comprised two rectal swabs that harboured isolates of different SNP-based MLST genotypes; however, the AMR susceptibility profiles of the different genotypes from these samples were indistinguishable. Within-sample differences in the AMR susceptibility profiles were observed for a further seven samples; however, the differences were not considered significant; MIC values were typically within a 2-fold difference or were close to test breakpoints. CONCLUSIONS: Results of this study provide further evidence that mixed-strain gonococcal infections do occur, although at low prevalence. Our data indicate that at a population level such infections are unlikely to impact significantly upon N. gonorrhoeae AMR surveillance.

Systemic capillary leak syndrome in a patient treated with nivolumab/ipilimumab immunotherapy for metastatic melanoma with concurrent COVID-19 vaccination.

Systemic capillary leak syndrome (SCLS) is a rare and life-threatening disorder characterised by leaking of intravascular fluid to extravascular tissues. An association with immunotherapy and COVID-19 vaccination has been reported as potential triggers. A case of a patient in her 70s developing SCLS after the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination with a history of metastatic melanoma treated with nivolumab (PD-1 monoclonal antibody) and ipilimumab (anti-CTLA4 monoclonal antibody) is reported. The aetiology and management of SCLS are also reviewed in this case context.

Risk factors for mortality in severe COVID-19: Exploring the interplay of immunomodulatory therapy and coinfection.

Patients with severe clinical manifestations of coronavirus disease 2019 (COVID-19) present particular diagnostic and management challenges to critical care physicians, including identifying and responding to concurrent bacterial and fungal coinfections. This study evaluates risk factors for in-hospital mortality in patients admitted to the intensive care unit with severe COVID-19 during circulation of the B.1.617.2 (Delta) variant, including the impact of immunomodulators and bacterial and/or fungal coinfection. This retrospective cohort study enrolled patients with severe COVID-19. A Cox proportional hazard ratio analysis identified risk factors for in-hospital mortality. Outcomes were also compared between patients receiving and not receiving immunomodulatory therapy alongside standard care. Ninety patients admitted to the intensive care unit were enrolled. On multivariate analysis, the greatest risk factors for in-hospital mortality were invasive mechanical ventilation (hazard ratio (HR) = 15.27; 95% confidence interval (CI) 3.29-71.0; P < 0.001), elevated body mass index (HR = 1.07 per unit; 95% CI 1.02-1.13; P = 0.007) and older age (HR = 1.53 per decade; 95% CI 1.05-2.24; P = 0.028). Bacterial and/or fungal coinfection occurred at equal frequency in patients receiving and not receiving immunomodulatory therapy. However, in patients receiving immunomodulators, coinfection carried a significantly higher mortality risk (63.0%) compared with those without coinfection (15.4%; P = 0.038). Mortality from severe COVID-19 is significantly higher in older patients and those with elevated body mass index and requiring mechanical ventilation. Immunomodulatory therapy necessitates vigilance towards evolving coinfection in the intensive care setting.

Psittacosis contagion in 1930: an old story in a new era of zoonotic disease.

The SARS-CoV-2 pandemic has highlighted the importance of zoonotic diseases. Psittacosis, a human disease resulting from infection spill-over from Chlamydia psittaci-infected birds, is a lesser-known example of a zoonosis. Psittacosis was responsible for numerous outbreaks in the 1930s, characterised by significant human mortality and disruption to the global trade in parrots. This paper describes the epidemiological and clinical details of one family group impacted by the purchase of an infected, imported parrot. Findings are discussed in the context of a growing awareness of the health risks of global disease outbreaks, as well as social and economic impacts. Health information recorded for cases of psittacosis associated with the 1930 cluster was reviewed using contemporary knowledge of disease symptoms and epidemiology. Case details and autopsy reports were examined. Public health investigation deduced that the cluster of infections was chronologically and physically connected to the purchase and subsequent death of an imported parrot. Disease symptoms were consistent with C. psittaci infection. Epidemiological data supported the diagnoses and causes of death, despite the presenting symptoms sharing significant overlap with other common respiratory diseases. There is growing awareness of the risks of epidemiological bridges in transmitting animal diseases to humans. Historical cases are a strong reminder of the fundamental role of scientific and public health responses in the face of such contagion.

Detection and characterisation of Bordetella hinzii in line-related bacteraemia and respiratory tract infection in Australia.

Bordetella hinzii has emerged as an unusual cause of infection in immunocompromised patients, previously linked to zoonotic transmission. Antimicrobial susceptibility and genetic diversity of B. hinzii are poorly understood. This study reports phenotypic and genomic characteristics of the first four Australian isolates of B. hinzii obtained from elderly immunocompromised patients. Bordetella hinzii isolates were identified by MALDI-TOF and whole genome sequencing (WGS). Antibiotic susceptibility testing was performed using disk diffusion or E-test. Genomes of B. hinzii were analysed in global context. A phylogenetic tree was constructed of all isolates using Roary and a maximum-likelihood tree was generated from the core-snp alignment. Bordetella hinzii minimum inhibitory concentrations (MICs) were largely uniform with high MICs to ampicillin, ceftriaxone and ciprofloxacin and low MICs to meropenem and piperacillin-tazobactam. Genomic analysis of isolate sequences divided strains analysed into two phylogenetically distinct groups, with one Australian B. hinzii isolate (AUS-4) assigned to Group 1, and the remaining isolates (AUS1-AUS3 and AUS-5) to Group 2. Single nucleotide polymorphism (SNP) analysis revealed two isolates, AUS-1 and AUS-2, were closely related with 14 SNP differences between them. All other Australian isolates were unrelated to each and all other isolates from the international dataset. Bordetella hinzii appears to pose a risk to immunocompromised individuals but remains susceptible to extended spectrum ß-lactam and carbapenem antibiotics. Genomic analysis suggested a dissemination of genetically distinct strains.

Chlamydia trachomatis in fallopian tubes of women undergoing laparoscopy for ectopic pregnancy.

OBJECTIVES: To study whether Chlamydia trachomatis is absent or persists in a latent state in the fallopian tube at the time of laparoscopic salpingectomy for tubal ectopic pregnancy (EP). METHODS: We examined tissue of the fallopian tubes for the presence of C. trachomatis from women who underwent laparoscopic salpingectomy for EP. Presence or absence of C. trachomatis was assessed using both Probe Tec ET (define Tec and ET please) and real-time polymerase chain reaction (PCR) (Ausdiagnositic STD 6 assays) DNA amplification. RESULTS: Fresh tubal tissue from 17 women with histological confirmation of EP was examined in a hospital setting for the presence of C. trachomatis. The presence of C. trachomatis DNA was confirmed by PCR using a commercial test (BD ProbeTec ET System), and a real-time enhanced PCR able to detect few copies of the organism. Chlamydia DNA was detected in 0/16 tubal specimens, and in one case, the PCR analysis was not possible for presence of inhibitors. CONCLUSIONS: We did not find any evidence of latent infection of C. trachomatis in the fallopian tube at the time of laparoscopic salpingectomy for EP in our study. Although the numbers are small, our results suggest that EP can be considered a late complication of the tubal damage resulted from a previous acute Chlamydia infection and that EP may not be related to a latent persistence of Chlamydia in the fallopian tube.

Prompt control of a Serratia marcescens outbreak in a neonatal intensive care unit informed by whole-genome sequencing and comprehensive infection control intervention package.

Objective: This report describes a cluster of patients infected by Serratia marcescens in a metropolitan neonatal intensive care unit (NICU) and a package of infection control interventions that enabled rapid, effective termination of the outbreak. Design: Cross-sectional analytical study using whole-genome sequencing (WGS) for phylogenetic cluster analysis and identification of virulence and resistance genes. Setting: NICU in a metropolitan tertiary-care hospital in Sydney, Australia. Patients: All neonates admitted to the level 2 and level 3 neonatal unit. Interventions: Active inpatient and environmental screening for Serratia marcescens isolates with WGS analysis for identification of resistance genes as well as cluster relatedness between isolates. Planning and implementation of a targeted, multifaceted infection control intervention. Results: The cluster of 10 neonates colonized or infected with Serratia marcescens was identified in a metropolitan NICU. Two initial cases involved devastating intracranial infections with brain abscesses, highlighting the virulence of this organism. A targeted and comprehensive infection control intervention guided by WGS findings enabled termination of this outbreak within 15 days of onset. WGS examination demonstrated phylogenetic linkage across the cluster, and genomic unrelatedness of later strains identified in the neonatal unit and elsewhere. Conclusions: A comprehensive, multipronged, infection control package incorporating close stakeholder engagement, frequent microbiological patient screening, environmental screening, enhanced cleaning, optimization of hand hygiene and healthcare worker education was paramount to the prompt control of Serratia marcescens transmission in this neonatal outbreak. WGS was instrumental in establishing relatedness between isolates and identification of possible transmission pathways in an outbreak setting.

Circulation of enterovirus D68 (EV-D68) causing respiratory illness in New South Wales, Australia, between August 2018 and November 2019.

The incidence of enterovirus D68 (EV-D68) in New South Wales, Australia, is unknown. As part of a state-wide surveillance program, enterovirus positive diagnostic specimens were assessed from patients presenting to hospitals with respiratory and meningitis syndromes from August 2018 to November 2019. Diagnostic enterovirus positive samples were collected from 339 patients and re-extracted followed by targeted PCR across the whole EV-D68 genome (7.4 kb). Obtained amplicons (n=208) were sequenced using Illumina sequencing technology and the phylogenetic relationships analysed relative to EV-D68 Fermon strain. We identified EV-D68 in 31 patients, both children (n=27) and adults (n=4). Phylogenetically, the majority (n=30) were from subclade B3, the same as that causing outbreaks of EV-D68 across the USA and Europe during 2018. These data strengthen the importance of having an active enterovirus surveillance network.

Evaluation of the BioFire Blood Culture Identification 2 panel and impact on patient management and antimicrobial stewardship.

Bloodstream infection survival is linked to timely administration of optimal antimicrobial therapy. Commercial multiplex polymerase chain reaction (PCR) assays, such as the BioFire Blood Culture Identification Panel (BCID) used for the rapid diagnosis of bloodstream infections, have significantly improved the turnaround time for optimisation of antimicrobial therapy. Reported concordance with culture-based methods and multiplex PCR analysis is high and only limited by (1) the range of targets available on the multiplex panel; and (2) the complexity of microorganisms present in the blood culture specimen. In this study, we evaluated the use of the BioFire Blood Culture Identification 2 panel (BCID2), including an expanded repertoire of targets for Gram-positive and Gram-negative bacteria, yeast and antimicrobial resistance genes compared to the BCID panel. The BCID2 panel identified microorganisms in 39/42 (92.9%) blood cultures where monomicrobial growth was detected; the three unidentified blood cultures contained organisms not included in the BCID2 panel. Polymicrobial blood culture analysis revealed a lower degree of concordance (28.6%); however, most disagreement was due to the culture-based identification of off-panel microorganisms of low clinical significance. Turnaround time, from blood culture collection to organism identification on the blood cultures correctly identified by BCID2, was 24.6 (±16.8) hours for the BCID2 panel versus 38.2 (±21.9) hours for conventional methods. Analysis of the theoretical impact of the BCID2 identification on clinical management found therapy would be altered in 45.1% (23/51) of patients. The BCID2 panel is anticipated to improve the diagnosis and antimicrobial management of patients with serious bloodstream infections.

An Australian diagnostic microbiology surge response to the COVID-19 pandemic.

Diagnostic microbiology services form a critical component of the response to infectious disease outbreaks. Like previous respiratory virus pandemics, the COVID-19 pandemic has placed significant strains on the standing capacity of laboratories around the world. In this case study, we describe the surge response required by our laboratory to meet the fluctuating demand for SARS-CoV-2 in our regional pathology service in Western Sydney, Australia between March and May 2020. While the overall number of SARS-CoV-2 PCR positive cases was relatively low compared to other Australian local health districts, testing numbers were highly unpredictable and changed on a weekly basis as local outbreaks were detected. As with other laboratories, numerous other challenges were also faced during this period, including the requirement to introduce a new and unaccredited diagnostic PCR assay for SARS-CoV-2, local and global shortages of reagents for sampling and sample processing, and a significant institutional SARS-CoV-2 outbreak in our laboratory catchment area. A successful service delivery during this period could only be maintained by a dynamic whole-of-laboratory and organizational response including (1) operational changes to the hours of service and the expansion of diagnostic testing at our laboratory site and other sites within our organization (2) careful management of specialist staff and re-training and recruitment of additional staff (3) changes to laboratory workflows to improve SARS-CoV-2 PCR test turnaround time and to accommodate limits to precious laboratory reagents; (4) clear communication within our laboratory and the NSW Health Pathology organization; and (5) collaborative co-ordination and support by NSW Health Pathology.

Bacillus cereus bacteraemia complicated by a brain abscess in a pre-term neonate.

Bacillus cereus is a common laboratory and environmental contaminant. Reports of severe infections are mainly limited to immunocompromised individuals. In reported cases, the time interval between bacteraemia and neuro-invasion appears to be very short, highlighting the importance of rapid and definitive identification and susceptibility testing of invasive B. cereus. We report a case of a neonatal B. cereus bacteraemia complicated by a brain abscess from a neonatal intensive care unit. The neonate presented with bradycardia and desaturations with increased oxygen requirements. Initial blood culture detected B. cereus but was considered a contaminant. Repeated culturing of the Gram-positive rod was subsequently considered to be significant. Initial ultrasound head scans revealed echogenicity in the right posterior deep white matter. A large central cavity (5 mm diameter) could eventually be observed. The brain abscess resolved after surgical drainage and an extensive 6 weeks of antimicrobial therapy. This case study describes a rare event that illustrates the importance of rapid identification and susceptibility testing of invasive B. cereus isolates from immunocompromised patients.

Human pegivirus in brain tissue of a patient with encephalitis.

We describe a case of meningoencephalitis in which meta-transcriptomic (RNA) sequencing detected human pegivirus (HPgV) in brain tissue, cerebrospinal fluid, and serum in the absence of other pathogens. This is the first detection of HPgV in antemortem brain tissue, although it is uncertain whether HPgV is responsible for the observed encephalitis.