Publications by authors named "Howden B"

A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique - Quantitative Mutational Scan sequencing (QMS-seq) - that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E.

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Background: The Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) networks 'Seq4AMR' and 'B2B2B AMR Dx' were established to promote collaboration between microbial whole genome sequencing (WGS) and antimicrobial resistance (AMR) stakeholders. A key topic discussed was the frequent variability in results obtained between different microbial WGS-related AMR gene prediction workflows. Further, comparative benchmarking studies are difficult to perform due to differences in AMR gene prediction accuracy and a lack of agreement in the naming of AMR genes (semantic conformity) for the results obtained.

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Genomics is a cornerstone of modern pathogen epidemiology yet demonstrating transmission in a One Health context is challenging, as strains circulate and evolve within and between diverse hosts and environments. To identify phylogenetic linkages and better define relevant measures of genomic relatedness in a One Health context, we collated 5471 Escherichia coli genome sequences from Australia originating from humans (n = 2996), wild animals (n = 870), livestock (n = 649), companion animals (n = 375), environmental sources (n = 292) and food (n = 289) spanning over 36 years. Of the 827 multi-locus sequence types (STs) identified, 10 STs were commonly associated with cross-source genomic clusters, including the highly clonal ST131, pandemic zoonotic lineages such as ST95, and emerging human ExPEC ST1193.

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We describe an outbreak of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup C in Fiji. We created surveillance case definitions and collected data by using standard investigation forms. Bacterial identification, antimicrobial susceptibility testing, and PCR were performed in Fiji.

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Background: Fiji is a Pacific Island nation grappling with the increasing threat of antimicrobial resistance (AMR). While genomic technologies are increasingly utilised to understand the emergence and spread of AMR globally, its application to inform outbreak responses in low- and middle-income settings has not been reported.

Methods: Through an established capacity building program, suspected carbapenem-resistant organisms (CRO) identified at Colonial War Memorial Hospital in Fiji (Jan 2022-Oct 2023) underwent whole genome sequencing and analysis.

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Background: Carbapenemase-producing Enterobacterales (CPE) are an emerging public health concern globally as they are resistant to a broad spectrum of antibiotics. Colonisation with CPE typically requires patients to be managed under 'contact precautions', which creates additional physical bed demands in healthcare facilities.

Methods: This study examined the potential impact of revised isolation guidelines introduced in late 2023 in Victoria, Australia, that relaxed the requirement for indefinite isolation of CPE-colonised patients in contact precautions, based on admission of CPE-diagnosed cases prior to the guideline change.

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Article Synopsis
  • Salmonella enterica serovar Panama is a significant cause of invasive non-typhoidal salmonellosis in Australia, despite being understudied, with a high incidence rate linked to international travel.
  • A study analyzed genomic epidemiology and antimicrobial resistance in S. Panama isolates in Victoria from 2000 to 2021, finding that over half exhibited multi-drug resistance, and colistin resistance was identified in one isolate.
  • The research also explored the growth dynamics of S. Panama in macrophages, revealing its ability to replicate more effectively compared to S. enterica serovar Typhimurium, although no specific genotype was linked to this enhanced replication.
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Objectives: The emergence of multidrug-resistant tuberculosis (MDR-TB) has made the elimination of TB difficult. Currently, there are limited data on MDR-TB and other drug-resistant TB in Bhutan. We aimed to estimate the incidence and explore the potential risk factors associated with MDR/pre-extensively drug-resistant (pre-XDR)-TB using comprehensive national TB data.

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The bacterium Vibrio parahaemolyticus is ubiquitous in tropical and temperate waters throughout the world and causes infections in humans resulting from water exposure and from ingestion of contaminated raw or undercooked seafood, such as oysters. We describe a nationwide outbreak of enteric infections caused by Vibrio parahaemolyticus in Australia during September 2021-January 2022. A total of 268 persons were linked with the outbreak, 97% of whom reported consuming Australia-grown oysters.

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Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease, causes cross-resistance to daptomycin in VREfm.

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Interpreting the phenotypes of alleles in genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal alleles or additional plasmid-borne alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood.

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Article Synopsis
  • Cholera, caused by a Gram-negative bacterium, is a significant public health issue with millions of annual cases, primarily linked to the ongoing seventh pandemic El Tor (7PET) lineage.
  • Research involving 34 bacterial isolates from travelers returning to Australia revealed that most belonged to non-7PET lineages, which still demonstrated antibiotic resistance and virulence factors.
  • The study highlights how travel impacts the spread of both epidemic and non-epidemic cholera strains, emphasizing the importance of surveillance in understanding and monitoring disease diversity and transmission.
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Article Synopsis
  • - The Australian Pathogen Genomics Program (AusPathoGen) was launched in January 2021 as a national partnership aimed at enhancing public health through pathogen genomics surveillance.
  • - Successful implementation of this program relies on collaboration among academia, public health labs, and agencies, while prioritizing public health needs and building national genomics capacity.
  • - Key components for success include data integration tools like AusTrakka, standardized bioinformatics procedures, ethics agreements, and training for public health officials to effectively use genomic data.
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N. gonorrhoeae, which causes the sexually transmissible infection gonorrhoea, remains a significant public health threat globally, with challenges posed by increasing transmission and antimicrobial resistance (AMR). The COVID-19 pandemic introduced exceptional circumstances into communicable disease control, impacting the transmission of gonorrhoea and other infectious diseases.

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Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019.

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Staphylococcus aureus is a major cause of neonatal infections in various anatomical sites, resulting in high morbidity and mortality in The Gambia. These clinical infections are often preceded by nasal carriage of S. aureus, a known risk factor.

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Background: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms.

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Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S.

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Whole genome sequencing (WGS) has become a vital tool in clinical microbiology, playing an important role in outbreak investigations, molecular surveillance, and identification of bacterial species, resistance mechanisms and virulence factors. However, the complexity of WGS data presents challenges in interpretation and reporting, requiring tailored strategies to enhance efficiency and impact. This study explores the diverse needs of key stakeholders in healthcare, including clinical management, laboratory work, public surveillance and epidemiology, infection prevention and control, and academic research, regarding WGS-based reporting of clinically relevant bacterial species.

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Background: Hospitals in any given region can be considered as part of a network, where facilities are connected to one another - and hospital pathogens potentially spread - through the movement of patients between them. We sought to describe the hospital admission patterns of patients known to be colonised with carbapenemase-producing Enterobacterales (CPE), and compare them with CPE-negative patient cohorts, matched on comorbidity information.

Methods: We performed a linkage study in Victoria, Australia, including datasets with notifiable diseases (CPE notifications) and hospital admissions (admission dates and diagnostic codes) for the period 2011 to 2020.

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While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.

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Article Synopsis
  • Invasive meningococcal disease (IMD) rates surged in Australia from 2014 to 2017, largely due to rising infections from serogroups W and Y, prompting a study on genetic diversity in 2017 and 2018 using whole genome sequencing.
  • The study analyzed 440 Australian IMD isolates and 1737 international MenW:CC11 isolates, revealing that MenW, MenB, and MenY were the most common serogroups and identified 18 clonal complexes, with three (CC11, CC23, CC41/44) making up 78% of the isolates.
  • Findings showed that while MenB isolates were highly diverse, MenW and MenC were less
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NaHCO responsiveness is a novel phenotype where some methicillin-resistant (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO. NaHCO responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO-responsive strains with β-lactams was associated with faster clearance of bacteremia.

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Background: Limited data exist on the effects of intrapartum azithromycin on the prevalence of carriage and antibiotic resistance of Enterobacterales.

Methods: We conducted a randomized trial in The Gambia and Burkina Faso where women received intrapartum azithromycin (2 g) or placebo. We determined the impact of treatment on the prevalence of carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae by analyzing rectal swabs (RS), nasopharyngeal swabs (NPS), breast milk, and rectovaginal swabs (RVS).

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Objectives: We analysed 4 y of laboratory data to characterise the species and determine the antimicrobial susceptibility profiles of enterococci as human pathogens in Fiji. The study also investigated the molecular epidemiology amongst the subset of vancomycin-resistant enterococci (VRE).

Methods: This retrospective study reviewed bacteriological data from Colonial War Memorial Hospital (CWMH) and other healthcare facilities in the Central and Eastern divisions of Fiji.

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