Epidemiology, clinical outcomes and risk factors of third-generation cephalosporin-resistant Escherichia coli hospitalized infections in remote Australia-a case-control study.

Background: Incidence of third-generation cephalosporin-resistant (3GCR) Escherichia coli infections has increased in remote Australia from 2012 to 2018. Objectives: To describe the epidemiology of 3GCR E. coli in Central Australia. Methods: A case-control study was conducted in the primary Central Australian hospital. Patient characteristics, antibiotic usage and clinical outcomes were compared between adult hospitalizations with 3GCR and susceptible E. coli isolates in 2018-19. Poisson regression was used to compare the incidence of 3GCR hospitalizations between Indigenous and non-Indigenous individuals. Patient characteristics and antibiotic usage were tested for associations with 3GCR isolates using univariate analysis. Results: A total of 889 E. coli isolates were identified, of which 187 (21%) were 3GCR. The incidence of 3GCR E. coli infection was 2.15 per 1000 person-years, with an incidence rate ratio of 6.8 (95% CI 4.6-10.1) between Indigenous and non-Indigenous individuals. When compared with the control group, 3GCR E. coli infections were associated with a higher Charlson comorbidity index (CCI ≥3 in 30.7% versus 15.0%, P < 0.001) and were more commonly healthcare associated (52.4% versus 26.7%, P < 0.001). A higher 1 year mortality was observed in the 3GCR group after adjustment for comorbidity (OR = 4.43, P = 0.002), but not at 30 days (2.4% versus 0.0%, P = 0.2). The 3GCR group used more antibiotics in the past 3 months (OR = 5.75, P < 0.001) and 12 months (OR = 3.65, P < 0.001). Conclusions: 3GCR E. coli infections in remote Australia disproportionally affect Indigenous peoples and are associated with a high burden of comorbidities and antibiotic use. Strategies to enhance antimicrobial stewardship should be considered in this remote setting.

Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients-a population pharmacokinetic study.

OBJECTIVES: To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis. METHODS: A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total)  ≥100 mg/L] were simulated for various dosing strategies. RESULTS: Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations >5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by >10-fold during dialysis. CONCLUSIONS: A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.

Prediction accuracy of commonly used pneumonia severity scores in Aboriginal patients with severe community-acquired pneumonia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is highly prevalent in the Aboriginal population. Few pneumonia severity scores are validated in this population. AIMS: To assess the prediction accuracy of pneumonia severity scores in Aboriginal patients with SCAP and to identify risk factors for poor prognosis. METHODS: Retrospective cohort study examining Aboriginal patients admitted to the intensive care unit with confirmed SCAP between January 2011 and December 2014. Severity scores were calculated for SMARTCOP (systolic blood pressure, multi-lobar, albumin, respiratory rate, tachycardia, confusion, oxygenation and arterial pH), SMARTACOP (systolic blood pressure, multi-lobar, albumin, respiratory rate, tachycardia, Aboriginal status, confusion, oxygenation and arterial pH), CURB-65 (confusion, urea, respiratory rate, blood pressure and age ≥65 years), pneumonia severity index, Infectious Diseases Society of America and American Thoracic Society SCAP, and Acute Physiology and Chronic Health Evaluation (APACHE) II/III using medical records. Prediction accuracy of 30-day mortality and requirement for intensive respiratory and/or vasoactive support (IRVS) were assessed using logistic regression and the area under the receiver operating characteristic curve (AUROC). Multivariate analysis was used to test associations between poor prognosis and demographic/clinical variables. RESULTS: A total of 203 cases (49% women) was identified. Thirty-day mortality was 6.4% (n = 13), and 53% (n = 107) required IRVS. None of the tested pneumonia severity scores accurately predicted mortality. SMARTCOP and SMARTACOP predicted IRVS requirement with the highest diagnostic accuracy, but only achieved acceptable discrimination (P <0.001 and <0.001; AUROC = 0.74 and 0.75 respectively). APACHE II/III predicted both mortality (P = 0.003 and 0.001; AUROC = 0.74 and 0.73 respectively) and IRVS requirement (P <0.001 and <0.001; AUROC = 0.72 and 0.73 respectively). Multivariate analysis associated mortality with male gender, cirrhosis, immunosuppression and acidaemia, and IRVS requirement with multi-lobar pneumonia, hypotension and tachypnoea. Multivariate analysis for mortality and IRVS requirement achieved an AUROC of 0.93 and 0.87 respectively. CONCLUSION: None of the pneumonia severity scores accurately predicted mortality. We recommend SMARTACOP to predict IRVS requirement in Aboriginal patients with SCAP. Given Aboriginal patients are over-represented in Australian intensive care units, a new score is warranted for this understudied population.

Body fat prediction through feature extraction based on anthropometric and laboratory measurements.

Obesity, associated with having excess body fat, is a critical public health problem that can cause serious diseases. Although a range of techniques for body fat estimation have been developed to assess obesity, these typically involve high-cost tests requiring special equipment. Thus, the accurate prediction of body fat percentage based on easily accessed body measurements is important for assessing obesity and its related diseases. By considering the characteristics of different features (e.g. body measurements), this study investigates the effectiveness of feature extraction for body fat prediction. It evaluates the performance of three feature extraction approaches by comparing four well-known prediction models. Experimental results based on two real-world body fat datasets show that the prediction models perform better on incorporating feature extraction for body fat prediction, in terms of the mean absolute error, standard deviation, root mean square error and robustness. These results confirm that feature extraction is an effective pre-processing step for predicting body fat. In addition, statistical analysis confirms that feature extraction significantly improves the performance of prediction methods. Moreover, the increase in the number of extracted features results in further, albeit slight, improvements to the prediction models. The findings of this study provide a baseline for future research in related areas.

Epidemiology and microbiology of severe community-acquired pneumonia in Central Australia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) has high mortality and morbidity. AIMS: To describe the epidemiology and microbiology of SCAP in Central Australia. METHODS: A retrospective epidemiological study describing the characteristics, incidence rates (IR) and microbiological aetiology of SCAP in Central Australia. Adult patients admitted to Alice Springs Hospital Intensive Care Unit (ICU) between 2011 and 2014 that fitted the Infectious Diseases Society of America and American Thoracic Society definition of SCAP were included. Medical records were reviewed and compared between indigenous and non-indigenous patients. Primary outcomes were incidence rate and microbiological aetiology of SCAP. Secondary outcomes were 30-day mortality, and ICU and hospital length of stay (LoS). RESULTS: A total of 185 patents were included (156 indigenous; 29 non-indigenous). The overall SCAP IR per 1000 person-years was 3.24 (3.75 indigenous; 1.87 non-indigenous) with an IR difference of 2.71 after adjustment (P < 0.001). Those aged ≥50 years had an IR 74.8% higher than those younger. Male IR was 50% higher than females. There was a significant difference between indigenous and non-indigenous groups for age (48 vs 64 years), but not for 30-day mortality (7.7% vs 10.3%), ICU LoS (4.8 vs 4.6 days) and hospital LoS (10.9 vs 15.1 days) respectively. Likely causative pathogen(s) were identified in 117 patients; Streptococcus pneumoniae was the most common pathogen (28.2%), followed by Haemophilus influenzae (19.7%), Influenza A/B (16.2%) and Staphylococcus aureus (14.5%). CONCLUSION: A high incidence of SCAP was observed in Central Australia, disproportionately affecting the indigenous population. Prevention strategies are imperative, as well as early identification of SCAP and appropriate empiric antibiotic regimens.

The impact of infectious diseases consultation on the management and outcomes of Pseudomonas aeruginosa bacteraemia in adults: a retrospective cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB. METHODS: This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality. RESULTS: A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95-20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups. CONCLUSION: Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.

A textual-based featuring approach for depression detection using machine learning classifiers and social media texts.

Depression is one of the leading causes of suicide worldwide. However, a large percentage of cases of depression go undiagnosed and, thus, untreated. Previous studies have found that messages posted by individuals with major depressive disorder on social media platforms can be analysed to predict if they are suffering, or likely to suffer, from depression. This study aims to determine whether machine learning could be effectively used to detect signs of depression in social media users by analysing their social media posts-especially when those messages do not explicitly contain specific keywords such as 'depression' or 'diagnosis'. To this end, we investigate several text preprocessing and textual-based featuring methods along with machine learning classifiers, including single and ensemble models, to propose a generalised approach for depression detection using social media texts. We first use two public, labelled Twitter datasets to train and test the machine learning models, and then another three non-Twitter depression-class-only datasets (sourced from Facebook, Reddit, and an electronic diary) to test the performance of our trained models against other social media sources. Experimental results indicate that the proposed approach is able to effectively detect depression via social media texts even when the training datasets do not contain specific keywords (such as 'depression' and 'diagnose'), as well as when unrelated datasets are used for testing.

Evaluating antimicrobial prescribing practice in Australian remote primary healthcare clinics.

BACKGROUND: Inappropriate antimicrobial prescribing contributes to the emergence of antimicrobial resistance. Gaps exist in the understanding of antimicrobial prescribing in the remote setting. We aimed to assess adherence to guidelines and appropriateness of antimicrobial prescribing in Central Australia. METHODS: A retrospective study assessing antimicrobial prescriptions in ten Aboriginal clinics (three in remote communities and seven in regional centre) using a validated evaluation tool. Antimicrobials prescribed between 1 January-31 December 2018 were randomly selected for inclusion into the study. The main outcome measures were the rates of guideline adherence and inappropriate prescribing. RESULTS: A total of 180 prescriptions were included (96.1% Aboriginal, 32.2% male). Ninety-nine (55.0%) prescriptions were written by general practitioners (GPs), 57 (31.7%) by nurses and 24 (13.3%) by others. Forty-three (25.7%) assessable prescriptions were deemed inappropriate and 75 (44.4%) did not adhere to guidelines. Prescriptions written by GPs were less likely to adhere to guidelines, particularly GPs located in remote communities. The most common reasons for inappropriate prescribing were incorrect dosage/frequency and antimicrobial not indicated. Skin and soft-tissue infection was the commonest indication, with 29 of 41 (70.7%) prescriptions deemed appropriate. Prescriptions for lower respiratory-tract infection had the lowest rate of appropriateness, with one of seven prescriptions deemed appropriate (14.3%). Antimicrobials with the lowest rate of appropriateness were ciprofloxacin, amoxicillin-clavulanate and cefalexin, at 50%, 56%, and 62%, respectively. CONCLUSION: A quarter of antimicrobial prescriptions written in select remote central Australian Aboriginal primary healthcare clinics were deemed inappropriate. The implementation of a comprehensive antimicrobial stewardship program is recommended.

Human T-cell leukaemia virus type 1 associated pulmonary disease: clinical and pathological features of an under-recognised complication of HTLV-1 infection.

The lung is one of several organs that can be affected by HTLV-1 mediated inflammation. Pulmonary inflammation associated with HTLV-1 infection involves the interstitium, airways and alveoli, resulting in several clinical entities including interstitial pneumonias, bronchiolitis and alveolitis, depending on which structures are most affected. Augmentation of the inflammatory effects of HTLV-1 infected lymphocytes by recruitment of other inflammatory cells in a positive feedback loop is likely to underlie the pathogenesis of HTLV-1 associated pulmonary disease, as has been proposed for HTLV-1 associated myelopathy. In contrast to the conclusions of early case series, HTLV-1 associated pulmonary disease can be associated with significant parenchymal damage, which may progress to bronchiectasis where this involves the airways. Based on our current understanding of HTLV-1 associated pulmonary disease, diagnostic criteria are proposed.

Using an improved relative error support vector machine for body fat prediction.

BACKGROUND AND OBJECTIVE: The term 'obesity' refers to excessive body fat, and it is a chronic disease associated with various complications. Although a range of techniques for body fat estimation have been developed to assess obesity, they are typically associated with high-cost tests requiring special equipment. Accurate prediction of the body fat percentage based on easily accessed body measurements is thus important for assessing obesity and its related diseases. This paper presents an improved relative error support vector machine approach to predict body fat in a cost-effective manner. METHODS: Our proposed method introduces a bias error control term into its objective function to obtain an unbiased estimation. Feature selection is also utilised, by removing either redundant or irrelevant features without incurring much loss of information, to further improve the prediction accuracy. In addition, the Wilcoxon rank-sum test is used to validate if the performance of our proposed method is significantly better than other prediction models being compared. RESULTS: Experimental results based on four evaluation metrics show that the proposed method is able to outperform other prediction models under comparison. Considering the characteristics of different features (e.g., body measurements), we show that applying feature selection can further improve the prediction performance. Statistical analysis carried out confirms that our proposed method has obtained significantly better results than other compared methods. CONCLUSIONS: We have proposed a new approach to predict the body fat percentage effectively. This approach can provide a good reference for people to know their body fat percentage with easily accessed measurements. Statistical test results based on the Wilcoxon rank-sum test not only show that our proposed method has significantly better performance than other prediction models being compared, but also confirm the usefulness of incorporating feature selection into the proposed method.

HTLV-1c associated bronchiolitis in an Aboriginal man from central Australia.

We describe the first case of HTLV associated bronchiolitis to be associated with HTLV-1c subtype infection. An Aboriginal man with HTLV-1 infection was repeatedly admitted to Alice Springs Hospital, central Australia, with hypercapnic respiratory failure from the age of 28 years. High resolution CT chest findings were consistent with bronchiolitis and large numbers of lymphocytes were found in bronchoalveolar lavage fluid (BALF). After extensive investigations failed to find a cause, he was tested for HTLV-1 and found to have a high HTLV-1c proviral load (6.8 %) in peripheral blood leukocytes and in BALF (4.7 %). The administration of systemic corticosteroids resulted in a rapid clinical response; however, he did not continue treatment after discharge and died due to respiratory failure in the community.

Ocular Toxoplasmosis in a Tertiary Referral Center in Sydney Australia-Clinical Features, Treatment, and Prognosis.

PURPOSE: The aim of this study was to provide a retrospective analysis of the presentation, demographics, and treatment regimens for ocular toxoplasmosis at a large tertiary referral uveitis center. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 48 patients with ocular toxoplasmosis who presented to Sydney Eye Hospital participated in this study. METHODS: This is a retrospective review of patient files who presented to Sydney Eye Hospital between 2007 and 2016 with clinical features consistent with ocular toxoplasmosis. Baseline risk factors and treatment details were recorded and analyzed. Main outcome measures were visual acuity and relapse rate compared with other studies in ocular toxoplasmosis. RESULTS: The median age was 35.5 (interquartile range 21-50) with 30 (60%) patients having no previous symptomatic episodes or evidence of chorioretinal scarring. Visual acuity at presentation was 0.51 or 6/19 (SE 0.096) and at follow-up 0.31 or 6/12 (SE 0.094). Nine patients experienced a recurrence during the period of observation with median time to recurrence 2.2 years (SE 0.45) and the relapse rate was 0.09/person-years. Location of lesion was predominantly within the vascular arcades (n = 44) with macular involvement in 9 patients. Most patients received clindamycin therapy (n = 34) with pyrimethamine and sulfadiazine was used for those with macula involvement. CONCLUSIONS: Patients with ocular toxoplasmosis had fewer recurrences compared with other published series and had better visual recovery. The majority of patients received clindamycin and oral prednisolone which were well tolerated with pyrimethazine and sulfadiazine reserved for those with macula-involving disease.

Severe Eosinophilic Meningoencephalitis Secondary to Suspected Neuroangiostrongyliasis with a Good Clinical Outcome.

Angiostrongylus cantonensis has caused sporadic cases of eosinophilic meningoencephalitis in Sydney, Australia. We describe a 36-year-old man who presented subacutely with fevers, reduced level of consciousness, confusion, ophthalmoplegia, and urinary incontinence. He was diagnosed with severe eosinophilic meningoencephalitis secondary to suspected Angiostrongylus cantonensis based on clinical, serological, and radiological findings. The patient was treated with albendazole and prednisolone with full neurological recovery. Management of neuroangiostrongyliasis with anthelminthic is controversial as it is thought to cause worsened outcomes through inciting an inflammatory response as a result of parasite killing. We managed to successfully treat our patient using albendazole and prednisolone and achieved a good outcome.

Opportunistic assessment and treatment of people with hepatitis C virus infection admitted to hospital for other reasons: A prospective cohort study.

BACKGROUND: It will be essential to find novel ways to access, diagnose and treat people with Hepatitis C Virus (HCV) infection in Australia to achieve HCV elimination. AIM: We assessed the effectiveness of opportunistic HCV assessment and antiviral treatment in patients admitted to hospital for other reasons. METHODS: Patients with HCV infection were referred from inpatient services at a tertiary referral centre in Sydney. Patients were assessed for HCV treatment with transient elastography (TE), HCV genotype and a clinical assessment and a summary letter was generated for all patients with a general practitioner (GP). Patients were offered treatment commencement at hospital discharge or after discharge with their GP, the infectious diseases clinic or with a gastroenterologist if they had cirrhosis. The primary outcome was the proportion of eligible patients who commenced treatment. We also undertook an intention to treat (ITT), modified intent to treat (mITT) analysis for virologic outcome (SVR12) and per protocol cure rates. An assessment of potential efficiency gains was undertaken. RESULTS: A total of 100 patients with a positive HCV antibody test were enrolled, of whom 70 were viraemic. The cohort included a high proportion of people who currently or previously injected drugs, indigenous patients and people previously lost to follow-up from other services. Treatment was initiated in 46 (66%) patients. The ITT was 80.4% (37/46) and mITT rate was 84.1% (37/44).The per-protocol SVR12 rate was 94.9%. Two subjects with genotype 3 and cirrhosis failed treatment, two subjects died and five were lost to follow up. The key barrier to uptake of DAA was incomplete assessment. Key inefficiencies of this model of care included referral of non-viraemic subjects, limited TE access and virologic test turnaround times. CONCLUSION: This model of care can complement the current efforts to increase HCV treatment in the community for those who do not access care elsewhere or are lost to follow-up.

A rare case of Behçet disease with generalised myositis, cardiomyositis and necrotising fasciitis.

Behçet disease (BD) is a rare relapsing, multisystem vasculitis characterised by recurrent oral and genital ulcers, and uveitis. As an autoimmune small vessel vasculitis, BD can involve other organs including the skin, joints, nervous system, kidney and the gastrointestinal tract. This report describes a 40-year-old woman who presented with an uncommon feature of BD, namely myositis, and who went on to develop myocarditis and polymicrobial necrotising fasciitis. To the best of our knowledge, this is the first reported case of an immunocompromised-associated infection occurring in BD without concurrent immunosuppressive therapy.

Serum sickness-like reaction after influenza vaccination.

Serum sickness (SS) and SS-like reaction (SSLR) are rare immune complex-mediated hypersensitivity illnesses characterised by key features of fever, rash, polyarthralgia or polyarthritis. They are self-limiting with an excellent prognosis, settling as the antigen is cleared. We describe a 30-year-old man who presented with fever, rash, polyarthralgia and subcutaneous soft tissue swelling in his hands and feet at day 5 after influenza vaccination. A thorough investigation for infective and autoimmune causes for the presenting symptoms was negative. Given the temporal relationship between the symptoms and influenza vaccination, clinical evidence and biological plausibility of influenza vaccination causing SSLR, a clinical diagnosis of SSLR was made. The patient was treated with anti-histamines, non-steroidal anti-inflammatories and glucocorticoids with gradual resolution of symptoms over 5 weeks.