Diabetes and hyperglycaemia among hospitalised patients with COVID-19 in Western Sydney: a retrospective cohort study.

BACKGROUND: Diabetes has been recognised as a major risk factor for COVID-19 mortality and hospital complications in earlier studies. AIMS: To examine the characteristics of hospitalised COVID-19 patients with diabetes and the impact of diabetes and hyperglycaemia on hospital outcomes. METHODS: This was a retrospective cohort study. Admission glucose levels, HbA1c, diabetes status and hospital outcomes were determined for subjects admitted from June to November 2021 by matching a pathology data set, a clinical data set and the hospital administrative database. The outcomes of interest were death, intensive care unit (ICU) admission and length of stay (LOS). RESULTS: There were 1515 individuals admitted with COVID-19 with 49 deaths (3.2%) and 205 (13.5%) ICU admissions. The median length of hospital stay was 3.7 days. Three hundred and ten patients (20%) had diabetes, with 46 (15%) newly diagnosed. Patients with diabetes had a higher mortality than patients who did not have diabetes (8% vs 2%, P < 0.001), were more likely to be admitted to ICU (20% vs 12%, P = 0.001) and have longer median LOS stay (6.6 (interquartile range (IQR) 2.9-12.5) vs 2.9 (IQR 0.5-7.1) days, P < 0.001). In multivariate models, neither diabetes nor admission glucose predicted death. Admission glucose level but not diabetes was an independent predictor of ICU admission and LOS. CONCLUSIONS: There is a high prevalence of diabetes among patients hospitalised with COVID-19, with worse outcomes. In contrast to previous studies, the association of diabetes with mortality was not significant when adjusted for other variables. This is possibly related to the benefits of vaccination and current medical and ICU interventions.

COVID-19 in Australia: our national response to the first cases of SARS-CoV-2 infection during the early biocontainment phase.

BACKGROUND: On 31 December 2019, the World Health Organization recognised clusters of pneumonia-like cases due to a novel coronavirus disease (COVID-19). COVID-19 became a pandemic 71 days later. AIM: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia. METHODS: This is a retrospective, multi-centre case series. All patients with confirmed COVID-19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. RESULTS: The median age of the patient cohort was 42 years (interquartile range (IQR), 24-53 years) with six men and five women. Eight (72.7%) patients had returned from Wuhan, one from Shenzhen, one from Japan and one from Europe. Possible human-to-human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co-morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75-21), all patients were discharged. CONCLUSIONS: This is a historical record of the first COVID-19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID-19 models of care and informing the management of COVID-19 over time as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection.

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).

Rapid Detection of Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus Directly from Positive Blood Cultures by Use of the BD Max StaphSR Assay.

The BD Max StaphSR assay is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). A total of 460 specimens were tested, and the results were compared with standard culture-based identification. MRSA was detected in 48 samples (sensitivity of 100%; positive predictive value [PPV] of 100%). MSSA was detected in 112 samples (sensitivity of 99.1%; PPV of 100%), and 299 samples containing coagulase-negative staphylococcus and nonstaphylococcal species were negative by the BD Max StaphSR assay (specificity of 100%; negative predictive value [NPV] of 99.7 to 100%).

Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates.

An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.

The seroprevalence of SARS-CoV-2-specific antibodies in Australian children: A cross-sectional study.

BACKGROUND: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated. OBJECTIVE: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years. METHODS: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0-19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and blood samples tested using the Roche Elecsys Anti-SARS-CoV-2 total spike and nucleocapsid antibody assays. Spike and nucleocapsid seroprevalence adjusted for geographic and socioeconomic imbalances in the participant sample compared to the Australian population was estimated using multilevel regression and poststratification within a Bayesian framework. RESULTS: Blood was collected from 2,046 participants (median age: 6.6 years). The overall adjusted seroprevalence of spike-antibody was 92.1% (95% credible interval (CrI) 91.0-93.3%) and nucleocapsid-antibody was 67.0% (95% CrI 64.6-69.3). In unvaccinated children spike and nucleocapsid antibody seroprevalences were 84.2% (95% CrI 81.9-86.5) and 67.1% (95%CrI 64.0-69.8), respectively. Seroprevalence was similar across geographic remoteness index and socioeconomic quintiles. Nucleocapsid antibody seroprevalence increased with age while the point seroprevalence of the spike antibody seroprevalence decreased in the first year of life and then increased to 97.8 (95% Crl 96.1-99.2) by 12-15 years of age. CONCLUSION: Most Australian children and adolescents aged 0-19 years, across all jurisdictions were infected with SARS-CoV-2 by August 2022, suggesting rapid and uniform spread across the population in a very short time period. High seropositivity in unvaccinated children informed COVID-19 vaccine recommendations in Australia.

Software for selecting the most informative sets of genomic loci for multi-target microbial typing.

BACKGROUND: High-throughput sequencing can identify numerous potential genomic targets for microbial strain typing, but identification of the most informative combinations requires the use of computational screening tools. This paper describes novel software-- Automated Selection of Typing Target Subsets (AuSeTTS)--that allows intelligent selection of optimal targets for pathogen strain typing. The objective of this software is to maximise both discriminatory power, using Simpson's index of diversity (D), and concordance with existing typing methods, using the adjusted Wallace coefficient (AW). The program interrogates molecular typing results for panels of isolates, based on large target sets, and iteratively examines each target, one-by-one, to determine the most informative subset. RESULTS: AuSeTTS was evaluated using three target sets: 51 binary targets (13 toxin genes, 16 phage-related loci and 22 SCCmec elements), used for multilocus typing of 153 methicillin-resistant Staphylococcus aureus (MRSA) isolates; 17 MLVA loci in 502 Streptococcus pneumoniae isolates from the MLVA database (http://www.mlva.eu) and 12 MLST loci for 98 Cryptococcus spp. isolates.The maximum D for MRSA, 0.984, was achieved with a subset of 20 targets and a D value of 0.954 with 7 targets. Twelve targets predicted MLST with a maximum AW of 0.9994. All 17 S. pneumoniae MLVA targets were required to achieve maximum D of 0.997, but 4 targets reached D of 0.990. Twelve targets predicted pneumococcal serotype with a maximum AW of 0.899 and 9 predicted MLST with maximum AW of 0.963. Eight of the 12 MLST loci were sufficient to achieve the maximum D of 0.963 for Cryptococcus spp. CONCLUSIONS: Computerised analysis with AuSeTTS allows rapid selection of the most discriminatory targets for incorporation into typing schemes. Output of the program is presented in both tabular and graphical formats and the software is available for free download from http://www.cidmpublichealth.org/pages/ausetts.html.