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Background The global emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has seen the dominance of specific clones in different regions around the world with the PVL-positive ST93-IV as the predominant CA-MRSA clone in Australia. In this study we applied a genome-wide association study (GWAS) approach on a collection of Australian ST93-IV MRSA genomes to screen for genetic traits that might have assisted the ongoing transmission of ST93-IV in Australia. We also compared the genomes of ST93-IV bacteraemia and non-bacteraemia isolates to search for potential virulence genes associated with bacteraemia. Results Based on single nucleotide polymorphism phylogenetics we revealed two distinct ST93-IV clades circulating concurrently in Australia. One of the clades contained isolates primarily isolated in the northern regions of Australia whilst isolates in the second clade were distributed across the country. Analyses of the ST93-IV genome plasticity over a 15-year period (2002–2017) revealed an observed gain in accessory genes amongst the clone’s population. GWAS analysis on the bacteraemia isolates identified two gene candidates that have previously been associated to this kind of infection. Conclusions Although this hypothesis was not tested here, it is possible that the emergence of a ST93-IV clade containing additional virulence genes might be related to the high prevalence of ST93-IV infections amongst the indigenous population living in the northern regions of Australia. More importantly, our data also demonstrated that GWAS can reveal candidate genes for further investigations on the pathogenesis and evolution of MRSA strains within a same lineage.

Antimicrobials are an integral component of healthcare delivery. When resistance to an antimicrobial emerges, it has a significant impact on an individual’s treatment and the community more broadly. In Australia, to monitor antimicrobial resistance in human health, the Australian Group on Antimicrobial Resistance (AGAR) performs three ongoing blood-based antimicrobial surveillance programs: the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP); the Australian Enterococcal Surveillance Outcome Program (AESOP); and the Gram-negative Surveillance Outcome Program (GnSOP). All data are available on the AGAR website and are included in the Australian Government Department of Health and Aged Care’s Antimicrobial Use and Resistance in Australia Surveillance System.

The past decade has seen an increase in the prevalence of sequence type (ST) 45 methicillin-resistant Staphylococcus aureus (MRSA), yet the underlying drivers for its emergence and spread remain unclear. To better understand the worldwide dissemination of ST45 S. aureus , we performed phylogenetic analyses of Australian isolates, supplemented with a global population of ST45 S. aureus genomes. Our analyses revealed a distinct lineage of multidrug-resistant ST45 MRSA harbouring qacA , predominantly found in Australia and Singapore. Bayesian inference predicted that the acquisition of qacA occurred in the late 1990s. qacA was integrated into a structurally variable region of the chromosome containing Tn 552 (carrying blaZ ) and Tn 4001 (carrying aac(6 ’ )-aph(2 ” ) ) transposable elements. Using mutagenesis and in vitro assays, we provide phenotypic evidence that qacA confers tolerance to chlorhexidine. These findings collectively suggest both antimicrobial resistance and the carriage of qacA may play a role in the successful establishment of ST45 MRSA. A study underscores the emergence of a qacA -harbouring multidrug-resistant sequence type 45 methicillin-resistant  Staphylococcus aureus lineage, highlighting the potential impact of biocide tolerance on its recent clonal spread in Australia and Asia.

Abstract Background and objectives There are few Australian data regarding the burden of hospital-onset bloodstream infections (HO-BSIs). To quantify the impact of antimicrobial-susceptible and -resistant HO-BSIs on patient outcomes by augmenting laboratory-based surveillance data. Methods We performed a retrospective cohort study at a tertiary referral hospital in Melbourne, Australia, from 2015 to 2020. We linked administrative data with bloodstream infection surveillance data from the Australian Group on Antimicrobial Resistance. We performed cause-specific Cox proportional hazards regression to quantify the impact of HO-BSI on inpatient mortality and discharge alive, with separate models for Enterobacterales, Staphylococcus aureus, Enterococcus species and the non-fermenting Gram-negative bacilli (NFGNB), Pseudomonas aeruginosa and Acinetobacter species, compared to admissions without HO-BSI. Excess length of stay (LOS) was estimated using multistate models. Results The cohort of 278 984 admissions included 814 (0.3%) HO-BSIs. Enterobacterales were the most frequent pathogens, followed by enterococci, S. aureus and NFGNB (incidence 3.62, 2.34, 1.11 and 0.80 events per 10 000 patient-days, respectively). Both antimicrobial-resistant and -susceptible HO-BSI increased risk of death and LOS compared with admissions without HO-BSI. Antimicrobial-resistant and -susceptible HO-BSIs, respectively, increased LOS by 5.7 days (95% CI: 4.9–6.5) and 4.1 days (95% CI: 3.8–4.5) for Enterobacterales, 4.9 days (95% CI: 4.5–5.4) and 3.1 days (95% CI: 2.6–3.6) for enterococci, and 6.3 days (95% CI: 5.3–7.3) and 9.8 days (95% CI: 9.1–10.5) for S. aureus. Conclusions Antimicrobial-susceptible and -resistant HO-BSIs have a substantial impact on patient outcomes. We demonstrated the feasibility of leveraging a national laboratory-based surveillance system to quantify the impact of HO-BSI.

IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Over the last three decades, hospital adapted clonal complex (CC) 17 strains of Enterococcus faecium have acquired and exchanged antimicrobial resistance genes leading to the widespread resistance to clinically important antimicrobials globally. In Australia, a high prevalence of vancomycin resistance has been reported in E. faecium in the last decade. In this study, we determined the phylogenetic relationship and genetic characteristics of E. faecium collected from hospitalized patients with blood stream infections throughout Australia from 2015 to 2017 using high throughput molecular techniques. Using single nucleotide polymorphism based phylogenetic inference, three distinct clusters of isolates were observed with additional sub-clustering. One cluster harboured mostly non-CC17 isolates while two clusters were dominant for the vanA and vanB operons. The gradual increase in dominance of the respective van operon was observed in both the vanA and vanB dominant clusters suggesting a strain-van operon affinity. The high prevalence of the van operon within isolates of a particular sub-cluster was linked to an increased number of isolates and 30-day all-cause mortality. Different dominant sub-clusters were observed in each region of Australia. Findings from this study can be used to put future surveillance data into a broader perspective including the detection of novel E. faecium strains in Australia as well as the dissemination and evolution of each strain.

Background: Antimicrobial resistance (AMR) is widely considered to be driven by antimicrobial consumption through within-host selection. However, whether this mechanism adequately explains population-level patterns of resistance in invasive infections remains uncertain. If antimicrobial use is the dominant determinant, resistance should be highest in demographic groups with the greatest exposure. Methods: We conducted a retrospective analysis of 44,792 community-onset Escherichia coli bloodstream infection episodes identified through national Australian surveillance data (2013–2024). Resistance prevalence across individual antimicrobials and composite multidrug resistance panels was analysed by age and sex. These data were compared with community antimicrobial dispensing derived from the Pharmaceutical Benefits Scheme. Mean resistance was modelled as a function of age and sex. Results: Antimicrobial use was substantially higher in females than males (~23% overall) and increased markedly with age, with individuals aged ≥80 years receiving approximately three times more antimicrobials than those aged 25–30 years. In contrast, resistance was consistently lower in females across most antimicrobials and composite measures. Resistance demonstrated an inverted U-shaped age distribution, peaking at 30–40 years before declining in older age groups. From early adulthood to older age, antimicrobial dispensing increased threefold, whereas mean resistance declined by approximately 20%. These patterns were consistent across antimicrobial classes, years, and jurisdictions. Conclusions: These findings show that demographic patterns of antimicrobial resistance in community-onset E. coli bloodstream infections are not well explained by a simple population-level consumption model. These findings should be interpreted as important hypothesis-generating insights. Although antimicrobial exposure remains important for individual-level selection, the observed discordance between prescribing and resistance suggests that other factors, including differences in transmission pathways, healthcare contact, disease prevalence, community sanitation and socioeconomic circumstances may also significantly shape resistance patterns.

Background Genetic variants at the vitamin D receptor (VDR) locus are associated with asthma and atopy. We hypothesized that polymorphisms in other genes of the vitamin D pathway are associated with asthma or atopy. Methods Eleven candidate genes were chosen for this study, five of which code for proteins in the vitamin D metabolism pathway ( CYP27A1 , CYP27B1 , CYP2R1 , CYP24A1 , GC ) and six that are known to be transcriptionally regulated by vitamin D ( IL10 , IL1RL1 , CD28 , CD86 , IL8 , SKIIP ). For each gene, we selected a maximally informative set of common SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. A total of 87 SNPs were genotyped in a French-Canadian family sample ascertained through asthmatic probands (388 nuclear families, 1064 individuals) and evaluated using the Family Based Association Test (FBAT) program. We then sought to replicate the positive findings in four independent samples: two from Western Canada, one from Australia and one from the USA (CAMP). Results A number of SNPs in the IL10 , CYP24A1 , CYP2R1 , IL1RL1 and CD86 genes were modestly associated with asthma and atopy (p < 0.05). Two-gene models testing for both main effects and the interaction were then performed using conditional logistic regression. Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002). In the replicate samples, SNPs in the IL10 and CYP24A1 genes were again modestly associated with asthma and atopy (p < 0.05). However, the SNPs or the orientation of the risk alleles were different between populations. A two-gene model involving IL10 and VDR was replicated in CAMP, but not in the other populations. Conclusion A number of genes involved in the vitamin D pathway demonstrate modest levels of association with asthma and atopy. Multilocus models testing genes in the same pathway are potentially more effective to evaluate the risk of asthma, but the effects are not uniform across populations.

DNA methylation (DNAm) is a dynamic, age-dependent epigenetic modification that can be used to study interactions between genetic and environmental factors. Environmental exposures during critical periods of growth and development may alter DNAm patterns, leading to increased susceptibility to diseases such as asthma and allergies. One method to study the role of DNAm is the epigenetic clock—an algorithm that uses DNAm levels at select age-informative Cytosine-phosphate-Guanine (CpG) dinucleotides to predict epigenetic age (EA). The difference between EA and calendar age (CA) is termed epigenetic age acceleration (EAA) and reveals information about the biological capacity of an individual. Associations between EAA and disease susceptibility have been demonstrated for a variety of age-related conditions and, more recently, phenotypes such as asthma and allergic diseases, which often begin in childhood and progress throughout the lifespan. In this review, we explore different epigenetic clocks and how they have been applied, particularly as related to childhood asthma. We delve into how in utero and early life exposures (e.g., smoking, air pollution, maternal BMI) result in methylation changes. Furthermore, we explore the potential for EAA to be used as a biomarker for asthma and allergic diseases and identify areas for further study.