One Health Determinants of Escherichia coli Antimicrobial Resistance in Humans in the Community:An Umbrella Review

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on “antibiotic resistance” and “systematic review” from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables.</p

Studies into the epidemiology and management of invasive fungal infections with a focus on candidaemia and antifungal resistance

Background Invasive fungal infections (IFIs) such as those caused by Candida species, the most common fungal pathogen, are associated with significant mortality despite advances in antifungal therapy and medical care. The aims of this thesis were to assess prevention in high-risk groups, examine the risk factors for candidaemia and its complications, and antifungal drug resistance. Methods The thesis employs a thesis-by-publication format, comprising four epidemiological studies followed by two laboratory-based studies. Findings In a retrospective single-centre analysis of itraconazole prophylaxis in acute myeloid leukaemia (AML), breakthrough IFI rate was low. A prospective multicentre, case-controlled study across Australia found that central venous access device (CVAD) use, end-organ failure, hepatobiliary or gastrointestinal surgery, urological instrumentation or catheterisation, intravenous drug use (IVDU) and carbapenem were risks factors for candidaemia. A case-cohort study identified age > 65 years, intensive care unit (ICU) admission, absence of prior surgery, haematological malignancy, chronic organ dysfunction, gastrointestinal or unidentifiable source and prior use of antibiotics for at least 10 days as associated with mortality, and established a predictive model. Shorter time to positivity (TTP) was associated with higher mortality, with species-specific differences. WGS of C. tropicalis demonstrated high-level fluconazole resistance present exclusively in isolates with ERG11 gene mutations in the homozygous form. An ERG3 deletion was associated with azole-resistance on comparison of two bloodstream isolates of C. albicans. Conclusions The thesis first provides support for the continued use of itraconazole prophylaxis for AML patients. The research contributed to the understanding of risk factors and outcomes associated with candidaemia and provided insights into the genomic characteristics associated with antifungal resistance

Multi-year antimicrobial-resistance trends in urine Escherichia coli isolates from both community-based and hospital-based laboratories of an Australian local health district

Objectives: Efforts to monitor and combat antimicrobial resistance (AMR) are typically focused on the hospital-based laboratory setting. The aim of this study was to longitudinally examine and compare trends in AMR among urine Escherichia coli isolates from a private community-based laboratory and a public hospital-based laboratory in an Australian local health district. Methods: A total of 108 262 urine E. coli isolates from a public hospital-based laboratory (N = 34 103) and a private community-based laboratory (N = 74 159) in a single health district between 2007–2019 were analysed. Linear regression was used to identify significance of change in AMR rates in both laboratories independently and detect any significant interaction of each setting in proportional change over the study period. Results: Similar AMR trends were detected among urinary E. coli isolates in private community-based laboratory and public hospital-based laboratory settings over 12 y. AMR rates were consistently higher in the public hospital-based setting. Ampicillin was the only antibiotic for which the E. coli resistance trend did not significantly change over the time period in either laboratory setting. All other antibiotics showed a significant increase in AMR rates over time in both settings. Conclusions: AMR rates in both the private community-based laboratory and public hospital-based laboratory settings increased over time and were consistently higher in the public hospital-based laboratory setting. Since private laboratories handle the vast majority of pathology volumes in community outpatient settings in Australia, interventions incorporating the community-based laboratory setting are critical to addressing AMR in the community

Multi-year antimicrobial-resistance trends in urine Escherichia coli isolates from both community-based and hospital-based laboratories of an Australian local health district

ABSTRACT: Objectives: Efforts to monitor and combat antimicrobial resistance (AMR) are typically focused on the hospital-based laboratory setting. The aim of this study was to longitudinally examine and compare trends in AMR among urine Escherichia coli isolates from a private community-based laboratory and a public hospital-based laboratory in an Australian local health district. Methods: A total of 108 262 urine E. coli isolates from a public hospital-based laboratory (N = 34 103) and a private community-based laboratory (N = 74 159) in a single health district between 2007–2019 were analysed. Linear regression was used to identify significance of change in AMR rates in both laboratories independently and detect any significant interaction of each setting in proportional change over the study period. Results: Similar AMR trends were detected among urinary E. coli isolates in private community-based laboratory and public hospital-based laboratory settings over 12 y. AMR rates were consistently higher in the public hospital-based setting. Ampicillin was the only antibiotic for which the E. coli resistance trend did not significantly change over the time period in either laboratory setting. All other antibiotics showed a significant increase in AMR rates over time in both settings. Conclusions: AMR rates in both the private community-based laboratory and public hospital-based laboratory settings increased over time and were consistently higher in the public hospital-based laboratory setting. Since private laboratories handle the vast majority of pathology volumes in community outpatient settings in Australia, interventions incorporating the community-based laboratory setting are critical to addressing AMR in the community

What’s New in <i>Cryptococcus gattii</i>: From Bench to Bedside and Beyond

Cryptococcus species are a major cause of life-threatening infections in immunocompromised and immunocompetent hosts. While most disease is caused by Cryptococcus neoformans, Cryptococcus gattii, a genotypically and phenotypically distinct species, is responsible for 11–33% of global cases of cryptococcosis. Despite best treatment, C. gattii infections are associated with early mortality rates of 10–25%. The World Health Organization’s recently released Fungal Priority Pathogen List classified C. gattii as a medium-priority pathogen due to the lack of effective therapies and robust clinical and epidemiological data. This narrative review summarizes the latest research on the taxonomy, epidemiology, pathogenesis, laboratory testing, and management of C. gattii infections

A series of three cases of severe Clostridium difficile infection in Australia associated with a binary toxin producing clade 2 ribotype 251 strain

Three patients with severe Clostridium difficile infection (CDI) caused by an unusual strain of C. difficile, PCR ribotype (RT) 251, were identified in New South Wales, Australia. All cases presented with severe diarrhoea, two had multiple recurrences and one died following a colectomy. C. difficile RT251 strains were isolated by toxigenic culture. Genetic characterisation was performed using techniques including toxin gene profiling, PCR ribotyping, whole genome sequencing (WGS), in-silico multi-locus-sequence-typing (MLST) and core-genome single nucleotide variant (SNV) analyses. Antimicrobial susceptibility was determined using an agar incorporation method. In vitro toxin production was confirmed by Vero cell cytotoxicity assay and pathogenicity was assessed in a murine model of CDI. All RT251 isolates contained toxin A (tcdA), toxin B (tcdB) and binary toxin (cdtA and cdtB) genes. Core-genome analyses revealed the RT251 strains were clonal, with 0–5 SNVs between isolates. WGS and MLST clustered RT251 in the same evolutionary clade (clade 2) as RT027. Despite comparatively lower levels of in vitro toxin production, in the murine model RT251 infection resembled RT027 infection. Mice showed marked weight loss, severe disease within 48 h post-infection and death. All isolates were susceptible to metronidazole and vancomycin. Our observations suggest C. difficile RT251 causes severe disease and emphasise the importance of ongoing surveillance for new and emerging strains of C. difficile with enhanced virulence

Anncaliia algerae Microsporidial Myositis, New South Wales, Australia

We describe the successful management of Anncaliia algerae microsporidial myositis in a man with graft versus host disease after hemopoietic stem cell transplantation. We also summarize clinical presentation and management approaches and discuss the importance of research into the acquisition of this infection and strategies for prevention