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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 Tn552 (carrying blaZ) and Tn4001 (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 FROM AUTHOR]

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000–2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7749 BSI in 5159 patients, 58% associated with neutropenia. Gram-negatives were the main causative pathogens (58.3%), more frequent in neutropenic than non-neutropenic patients (3308/5309, 62.3% vs 1932/3678, 52.5%, p < 0.001). Amongst 8987 isolates the most common were E.coli (15.4%) and Pseudomonas spp. (14.2%). Pseudomonas spp. (16.6% vs 10.7%, p < 0.001), Klebsiella spp. (11.6% vs 6.8%, p < 0.001), viridans-group streptococci (4.4% vs 1.2%, p < 0.001) and E.faecium (2.4% vs 0.9%, p < 0.001) were more common in neutropenic than non-neutropenic patients, while S.aureus was less common (5.9% vs 15.6%, p < 0.001). Several antimicrobial resistance rates increased over time and had higher prevalence in neutropenic than non-neutropenic patients, including ciprofloxacin-resistant E.coli (94/758, 12.4% vs 42/506, 8.3%, p = 0.021), trimethoprim-sulfamethoxazole-resistant E.coli (366/764, 47.9% vs 191/517, 36.9%, p < 0.001), penicillin-resistant streptococci (51/236, 21.6% vs 28/260, 10.8%, p < 0.001) and vancomycin-resistant enterococci (46/250, 18.4% vs 9/144, 6.3%, p < 0.001). Carbapenem-resistant Pseudomonas spp. (OR 7.32, 95%CI 2.78–19.32) and fungi, including yeasts and moulds (OR 3.33, 95%CI 2.02–5.48) were associated to the highest odds of 30-day case-fatality at a multivariable logistic regression analysis. Neutropenia was associated with survival (OR 0.66, 95%CI 0.55–0.78). Differences were observed in the BSI epidemiology according to neutropenic status, with an overall increase of resistance over time associated to adverse outcome. [ABSTRACT FROM AUTHOR]

Purpose of Review: To describe existing applications of artificial intelligence (AI) in sepsis management and the opportunities and challenges associated with its implementation in the paediatric intensive care unit. Recent Findings: Over the last decade, significant advances have occurred in the use of AI techniques, particularly in relation to medical image analysis. Increasingly, these techniques are being applied to a broad array of datasets. The availability of both structured and unstructured data from electronic health records, omics data and digital technologies (for example, portable sensors) is rapidly extending the range of applications for AI. These techniques offer the exciting potential to improve the recognition of sepsis and to help us understand the pathophysiological pathways and therapeutic targets of sepsis. Summary: Although AI has great potential to improve sepsis management in children, significant challenges need to be overcome before it can be successfully implemented to change healthcare delivery. [ABSTRACT FROM AUTHOR]

Purpose: Although Klebsiella aerogenes (formerly Enterobacter aerogenes) and Enterobacter cloacae share many phenotypic characteristics, controversy exists as to whether they cause clinically distinguishable infections. The objective of this study was to determine the comparative incidence, determinants, and outcomes of K. aerogenes and E. cloacae bloodstream infections (BSI). Methods: Population-based surveillance was conducted among residents aged ≥ 15 years of Queensland, Australia during 2000–2019. Results: Overall 695 and 2879 incident K. aerogenes and E. cloacae BSIs were identified for incidence rates of 1.1 and 4.4 per 100,000 population, respectively. There was a marked increase in incidence associated with older age and with males with both species. Patients with K. aerogenes BSIs were older, were more likely male, to have community-associated disease, and to have a genitourinary source of infection. In contrast, E. cloacae were more likely to have co-morbid diagnoses of liver disease and malignancy and be associated with antimicrobial resistance. Enterobacter cloacae were significantly more likely to have repeat episodes of BSI as compared to K. aerogenes. However, no differences in length of stay or all cause 30-day case-fatality were observed. Conclusion: Although significant demographic and clinical differences exist between K. aerogenes and E. cloacae BSI, they share similar outcomes. [ABSTRACT FROM AUTHOR]

The epidemiology of Moraxella species bloodstream infection (BSI) is poorly defined due to their rarity. We sought to determine the incidence, risk factors, and outcomes of Moraxella species BSI in a large Australian population. All Moraxella species BSIs in patients admitted to Queensland (population estimate 5 million) public health facilities between 2000 and 2019 and submitted to Queensland pathology laboratory-based surveillance were included. Clinical and hospitalisation data were matched with laboratory-based surveillance data. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were calculated. In total, 375 incident Moraxella species BSI occurred during 86 million person-years of surveillance, with an annualised age and sex standardised incidence of 4.3 per million residents. Isolates were most commonly identified as M. catarrhalis (n = 128; 34%) and community-associated (n = 225; 60%). Incidence was highest in infants, with increasing age associated with lower incidence rate. Males were at higher risk (incidence 2.9 vs. 2.0 per million, IRR1.4; 95% CI, 1.2–1.8), this was most pronounced at age extremes. Two-thirds of adults and 43% of children with Moraxella BSI had at least one comorbid illness. When compared to infections in adults, children were more likely to have community-associated disease, and a head and neck source focus of infection. The all-cause 30-day case-fatality rate was 4% (15/375) and this was significantly higher among adults (14/191; 7% vs 1/183; 1%; p < 0.001). Our findings demonstrate the low burden of Moraxella species BSI in a state-wide cohort, for which young children have the highest risk. [ABSTRACT FROM AUTHOR]

Although obesity is a major healthcare problem that is increasing in many populations worldwide, there are limited studies that have examined its contribution to infectious diseases morbidity and mortality. The aim of this study was to examine the clinical determinants and outcomes of bloodstream infections among patients with obesity. All adults within the publicly funded healthcare system in Queensland, Australia, identified with a BSI during 2017–2019 were included and the presence of obesity was based on discharge International Classification of Diseases (ICD-10) codes. Clinical features, microbiology, and outcomes were compared among obese and non-obese subjects. A total of 24,602 incident BSI were identified among 21,613 Queensland residents; of which 4,579 (21.2%) and 17,034 (78.8%) were classified as obese or non-obese, respectively. Obese patients were less likely to have community associated infections and were more likely to be younger, female, have higher comorbidity scores, and have bone and joint or soft tissue infections as compared to non-obese subjects. Obese patients had a lower proportion of Escherichia coli BSI and higher proportions of b-haemolytic streptococci. Although obese patients had longer hospital admissions and more repeat incident BSI within 1 year, they had lower overall case fatality. In a logistic regression model, obesity was associated with a lower risk for 30-day case fatality (adjusted odds ratio 0.51, 95% confidence interval 0.45–0.58). Obesity is associated with significant differences in the determinants and outcome of BSI. Increasing rates of obesity is likely to influence the epidemiology of BSI in populations. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing organisms (CPOs) pose a serious clinical threat and rapid detection tools are essential to aid in patient management. We developed rapid and simple molecular tests to detect blaNDM-type and blaVIM-type carbapenemase genes using recombinase polymerase amplification (RPA) combined with a lateral flow detection. The tests could provide results in approximately 15 min when using DNA extracts, with limits of detection of 9.2 copies/μl for the blaNDM-type assay and 7.5 copies/μl for blaVIM-type assay, and successfully detected all isolates harbouring the carbapenemase encoding genes in a panel of 57 isolates. These RPA tests may be suitable for use in low-resource settings to tailor rapid implementation of infection control precautions and antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Purpose of Review: The aim of this article is to review current and emerging microbiological techniques that support the rapid diagnosis of bacterial infections in critically ill patients, including their performance, strengths and pitfalls, as well as available data evaluating their clinical impact. Recent Findings: Bacterial infections and sepsis are responsible for significant morbidity and mortality in patients admitted to the intensive care unit and their management is further complicated by the increase in the global burden of antimicrobial resistance. In this setting, new diagnostic methods able to overcome the limits of traditional microbiology in terms of turn-around time and accuracy are highly warranted. We discuss the following broad themes: optimisation of existing culture-based methodologies, rapid antigen detection, nucleic acid detection (including multiplex PCR assays and microarrays), sepsis biomarkers, novel methods of pathogen detection (e.g. T2 magnetic resonance) and susceptibility testing (e.g. morphokinetic cellular analysis) and the application of direct metagenomics on clinical samples. The assessment of the host response through new "omics" technologies might also aid in early diagnosis of infections, as well as define non-infectious inflammatory states. Summary: Despite being a promising field, there is still scarce evidence about the real-life impact of these assays on patient management. A common finding of available studies is that the performance of rapid diagnostic strategies highly depends on whether they are integrated within active antimicrobial stewardship programs. Assessing the impact of these emerging diagnostic methods through patient-centred clinical outcomes is a complex challenge for which large and well-designed studies are awaited. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat to human health. Here we report the application of several complementary whole-genome sequencing (WGS) technologies to characterise a hospital outbreak of blaIMP-4 carbapenemase-producing E. hormaechei. Using Illumina sequencing, we determined that all outbreak strains were sequence type 90 (ST90) and near-identical. Comparison to publicly available data linked all outbreak isolates to a 2013 isolate from the same ward, suggesting an environmental source in the hospital. Using Pacific Biosciences sequencing, we resolved the complete context of the blaIMP-4 gene on a large IncHI2 plasmid carried by all IMP-4-producing strains across different hospitals. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90 E. hormaechei and the IncHI2 plasmid within the hospital plumbing. Finally, Oxford Nanopore sequencing rapidly resolved the true relationship of subsequent isolates to the initial outbreak. Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak. Antibiotic-resistant bacteria are an urgent threat to human health. Here, Roberts et al. characterise and monitor an ongoing hospital outbreak of carbapenemase-producing Enterobacter hormaechei by integrating several technologies for whole-genome sequencing and shotgun metagenomics. [ABSTRACT FROM AUTHOR]

Purpose: Rectal culture screening for fluoroquinolone (FQ)-resistant Enterobacteriaceae before transrectal ultrasound guided prostate (TRUSPB) biopsy and targeted antibiotic prophylaxis (TAP) may decrease post-TRUSPB infection rates compared to empiric (EAP) regimens. The objective of this study was to evaluate the effectiveness of targeted relative to empiric prophylaxis regimens on rates of infectious complications after TRUSPB and to determine the baseline prevalence of FQ resistance based on prior rectal swabs.Methods: An electronic search within literature databases including EMBASE and Web of Science (all databases) for articles assessing TAP as an approach to TRUSPB prophylaxis was conducted. Quality assessment was performed using the Hoy instrument. Meta-analysis was performed using MetaXL 5.3.Results: From 15 studies (eight retrospective and seven prospective) representing 12,320 participants, infectious complication incidence was 3.4% in EAP and 0.8% in TAP patients. The number needed to treat with TAP to avoid one more infection when compared to the EAP group was 39. Effect sizes were homogeneous. Prevalence of FQ resistance showed low (15%) and high (28%) subgroups, likely due to region of origin (within and outside USA, respectively).Conclusions: Rectal culture prior to TRUSPB and use of TAP adjusts for endemic FQ resistance and is associated with less infectious complications and resulting morbidity when compared to EAP. Overtreatment associated with augmented prophylaxis approaches may be reduced as a result. Further prospective assessment and cost-benefit analyses are required before widespread implementation can be recommended. [ABSTRACT FROM AUTHOR]

Purpose: To systematically review and meta-analyse available evidence comparing fosfomycin trometamol (FT) to fluoroquinolone (FQ) prophylaxis to prevent transrectal ultrasound-guided prostate biopsy (TRUSPB) related infectious complications. Methods: Electronic databases were queried for studies comparing FT to FQ-based TRUSPB prophylaxis. Studies were assessed for comparable outcomes and methodological quality (ROBINS-I modification). The primary outcome measure was the relative odds of overall infectious complications following TRUSPB according to FT/FQ treatment, which was evaluated with meta-analysis. Safety and tolerability were also assessed. The relative odds of infections of different severity [Grade 1, bacteriuria and afebrile urinary tract infection (UTI); Grade 2, bacteraemia, febrile UTI, and urosepsis] according to FT/FQ treatment were also estimated. Results: Five studies, being three prospective randomised trials and two retrospective cohort studies, representing 3112 patients, were included. The relative odds of an infectious complication (OR 0.22, 95% CI 0.09-0.54) or of a more severe (Grade 2) infection (OR 0.13, 95% CI 0.07-0.26) were significantly lower in those receiving FT compared to FQ prophylaxis. A low incidence of medication-related side effects was observed. There were less observed infections due to FQ-resistant pathogens in those receiving FT prophylaxis. Conclusions: Patients who received FT prophylaxis were less likely than those who received FQ prophylaxis to develop infections overall, as well as severe and resistant infections after TRUSPB. Assessing the performance of FT in other geographic locations or in comparison to targeted prophylaxis based on risk assessment or rectal cultures is desired. [ABSTRACT FROM AUTHOR]