205 results on '"Coombs GW"'
Search Results
2. Prevalence of MRSA among Staphylococcus aureus isolated from hospital inpatients, 2005: report from the Australian Group for Antimicrobial Resistance
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Australian Group for Antimicrobial Resistance, McLaws, ML, Coombs, GW, Collignon, PJ, Pearson, JC, Nimmo, GR, Christiansen, KJ, and Bell, JM
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- 2007
3. First report of a mecA -positive multidrug-resistant Staphylococcus pseudintermedius isolated from a dog in New Zealand.
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Bell, Ag, Coombs, Gw, Cater, B, and Douglass, C
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STAPHYLOCOCCUS ,PYODERMA ,ZOONOSES ,DIAGNOSIS ,PREVENTION - Abstract
CASE HISTORY: A 14-year-old neutered male Sealyham terrier was referred for assessment of a persistent pyoderma. It had experienced numerous episodes of dermatitis involving pododermatitis, pyoderma and otitis over the previous 6 years. CLINICAL FINDINGS: Superficial, focally deep and mucocutaneous pyoderma were present, with yellow mucoid exudate on both nares and the lower lips crusted with haemopurulent exudate. Epidermal collarettes were present on the dorsal and lateral trunk. There were peri-anal crusts and mild erythema was present on the concave aspect of both pinnae. MICROBIOLOGICAL FINDINGS: Culture and microbiological testing identifiedStaphylococcus pseudintermediusas the infecting organism. Kirby-Bauer disc susceptibility testing revealed the isolate was resistant to numerous antimicrobials including oxacillin. PCR testing of the isolate identified the presence of themecAgene which confers resistance to ?-lactam antimicrobials. Pulsed field gel electrophoresis typing suggested the isolate was not related to the methicillin-resistantS. pseudintermediusthat had been reported to be associated with canine infections in Western Australia. DIAGNOSIS: Superficial, deep and mucus membrane pyoderma associated with a multi-drug resistantS. pseudintermedius. CLINICAL RELEVANCE: This is the first recorded case of canine pyoderma involving methicillin-resistant multidrug-resistantS. pseudintermediusin New Zealand. Treatment of such cases is difficult because the number of effective and available antimicrobials is limited. This finding should raise the awareness of the veterinary and medical professions to the presence of such organisms in New Zealand and stimulate a discussion about possible biosecurity barriers, treatment strategies and prevention of zoonotic and nosocomial infections. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
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4. Antibiotic Choice May Not Explain Poorer Outcomes in Patients With Staphylococcus aureus Bacteremia and High Vancomycin Minimum Inhibitory Concentrations.
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Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, Anderson TL, Roberts SA, Gao W, Christiansen KJ, Coombs GW, Johnson PD, and Howden BP
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(See the editorial commentary by Holland and Fowler Jr, on pages 329-31.) Background. There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. Methods. We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. Results. We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 [mu]g/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not. Conclusions. We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome. [ABSTRACT FROM AUTHOR]
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- 2011
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5. Intrafamilial transmission of methicillin-resistant Staphylococcus aureus.
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Pozzi LS, Robinson JO, Pearson JC, Christiansen KJ, Coombs GW, Murray RJ, Pozzi Langhi, Sabrina A, Robinson, James O, Pearson, Julie C, Christiansen, Keryn J, Coombs, Geoffrey W, and Murray, Ronan J
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- 2009
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6. Antimicrobial resistance among clinically significant bacteria in wildlife: An overlooked one health concern.
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Li X, Mowlaboccus S, Jackson B, Cai C, and Coombs GW
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- Animals, Birds microbiology, Humans, Mammals microbiology, Reptiles microbiology, Bacterial Infections microbiology, Bacterial Infections veterinary, Bacterial Infections drug therapy, Global Health, Animals, Wild microbiology, One Health, Drug Resistance, Bacterial genetics, Bacteria drug effects, Bacteria genetics, Bacteria classification, Bacteria isolation & purification, Anti-Bacterial Agents pharmacology
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Antimicrobial resistance (AMR) has emerged as a critical global health challenge. However, the significance of AMR is not limited to humans and domestic animals but extends to wildlife and the environment. Based on the analysis of > 200 peer-reviewed papers, this review provides comprehensive and current insights into the detection of clinically significant antimicrobial resistant bacteria and resistance genes in wild mammals, birds and reptiles worldwide. The review also examines the overlooked roles of wildlife in AMR emergence and transmission. In wildlife, AMR is potentially driven by anthropogenic activity, agricultural and environmental factors, and natural evolution. This review highlights the significance of AMR surveillance in wildlife, identifies species and geographical foci and gaps, and demonstrates the value of multifaceted One Health strategies if further escalation of AMR globally is to be curtailed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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7. Australian Group on Antimicrobial Research surveillance outcome programs - bloodstream infections and antimicrobial resistance patterns from patients less than 18 years of age, January 2020 - December 2021.
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Williams A, Coombs GW, Bell J, Daley DA, Mowlaboccus S, Bryant PA, Campbell AJ, Cooley L, Iredell J, Irwin AD, Kesson A, McMullan B, Warner MS, Williams P, and Blyth CC
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- Humans, Adolescent, Child, Australia epidemiology, Child, Preschool, Infant, Male, Female, Drug Resistance, Multiple, Bacterial, Infant, Newborn, Gram-Negative Bacteria drug effects, Gram-Negative Bacteria isolation & purification, Drug Resistance, Bacterial, Anti-Bacterial Agents pharmacology, Bacteremia microbiology, Bacteremia epidemiology, Bacteremia drug therapy, Microbial Sensitivity Tests
- Abstract
Abstract: From 1 January 2020 to 31 December 2021, thirty-eight institutions across Australia submitted data to the Australian Group on Antimicrobial Resistance (AGAR) from patients aged < 18 years (AGAR-Kids). Over the two years, 1,679 isolates were reported from 1,611 patients. This AGAR-Kids report aims to describe the population of children and adolescents with bacteraemia reported to AGAR and the proportion of resistant isolates. Overall, there were 902 gram-negative isolates reported: 800 Enterobacterales , 61 Pseudomonas aeruginosa and 41 Acinetobacter spp. Among the Enterobacterales , 12.9% were resistant to third generation cephalosporins; 11.6% to gentamicin/tobramycin; and 11.2% to piperacillin-tazobactam. In total, 14.5% of Enterobacterales were multi-drug resistant (MDR). Only 3.3% of P. aeruginosa were resistant to carbapenems and 4.9% were MDR. Resistance in Acinetobacter spp was uncommon. Of 607 Staphylococcus aureus isolates, 12.9% were methicillin-resistant (MRSA). Almost half of S. aureus isolates from the Northern Territory were MRSA. In S. aureus , resistance to erythromycin was 13.2%; 12.4% to clindamycin; and 5.3% to ciprofloxacin. Resistance to all antibiotics tested was higher in MRSA. Overall, 6.5% of S. aureus were MDR, of which 65% were MRSA. Almost three-quarters of the 170 Enterococcus spp. reported were E. faecalis , and half were from patients < 1 year old. Ampicillin resistance in enterococci was 19.6%. Eight isolates were vancomycin resistant and three isolates were teicoplanin resistant. Five E. faecium isolates were classified as MDR. This AGAR-Kids report highlights clear differences in the geographic distribution of pathogens and resistance profiles across Australia., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2024
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8. Leveraging existing data to improve antimicrobial resistance-related mortality estimates for Australia.
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Wozniak TM, Nguyen A, Good N, and Coombs GW
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- Humans, Australia epidemiology, Anti-Bacterial Agents therapeutic use, Male, Female, Aged, Middle Aged, Adult, Drug Resistance, Bacterial
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Antimicrobial resistance (AMR) is a global pandemic, however, estimating its burden is a complex process. As a result, many countries rely on global estimates to infer burden within their own setting. With a growing number of recent publications quantifying AMR burden in Australia, and an expansion of surveillance programs, enumerating AMR mortality for Australia is feasible. We aimed to leverage existing published data to assess methodological factors contributing to the considerable variation in AMR-related mortality and provide two reliable estimates of AMR mortality in Australia. This is a necessary step towards generating meaningful measures of AMR burden in Australia.
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- 2024
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9. Non- faecium non- faecalis enterococci: a review of clinical manifestations, virulence factors, and antimicrobial resistance.
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Mullally CA, Fahriani M, Mowlaboccus S, and Coombs GW
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- Humans, Animals, Drug Resistance, Bacterial, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacology, Enterococcus pathogenicity, Enterococcus drug effects, Enterococcus genetics, Virulence, Gram-Positive Bacterial Infections microbiology, Gram-Positive Bacterial Infections drug therapy, Virulence Factors genetics
- Abstract
SUMMARYEnterococci are a diverse group of Gram-positive bacteria that are typically found as commensals in humans, animals, and the environment. Occasionally, they may cause clinically relevant diseases such as endocarditis, septicemia, urinary tract infections, and wound infections. The majority of clinical infections in humans are caused by two species: Enterococcus faecium and Enterococcus faecalis . However, there is an increasing number of clinical infections caused by non- faecium non- faecalis (NFF) enterococci. Although NFF enterococcal species are often overlooked, studies have shown that they may harbor antimicrobial resistance (AMR) genes and virulence factors that are found in E. faecium and E. faecalis . In this review, we present an overview of the NFF enterococci with a particular focus on human clinical manifestations, epidemiology, virulence genes, and AMR genes., Competing Interests: The authors declare no conflict of interest.
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- 2024
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10. Whole-genome sequencing identifies MprF mutations in a genetically diverse population of daptomycin non-susceptible Staphylococcus aureus in Australia.
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Lim C, Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
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- Humans, Australia, Male, Drug Resistance, Multiple, Bacterial genetics, Female, Genome, Bacterial genetics, Middle Aged, Aged, Adult, Daptomycin pharmacology, Whole Genome Sequencing, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Staphylococcus aureus drug effects, Staphylococcus aureus genetics, Staphylococcal Infections microbiology, Staphylococcal Infections drug therapy, Bacterial Proteins genetics, Mutation, Aminoacyltransferases genetics
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Objectives: Daptomycin is one of the few last-line antimicrobials available for the treatment of multidrug-resistant Staphylococcus aureus infections. An increasing number of daptomycin non-susceptible S. aureus infections has been reported worldwide, including Australia. Resistance to daptomycin is multifactorial and involves chromosomal mutations in genes encoding proteins involved in cell membrane and cell wall synthesis., Methods: In this study, we performed broth microdilution (BMD) to determine the daptomycin minimum inhibitory concentration (MIC) of 66 clinical isolates of S. aureus previously reported as daptomycin non-susceptible by the VITEK
Ⓡ 2. We used whole-genome sequencing to characterise the isolates and screened the genomes for mutations associated with daptomycin non-susceptibility., Results: Only 56 of the 66 isolates had a daptomycin MIC >1 mg/L by BMD. Although the 66 isolates were polyclonal, ST22 was the predominant sequence type and one-third of the isolates were multidrug resistant. Daptomycin non-susceptibility was primarily associated with MprF mutations-at least one MprF mutation was identified in the 66 isolates. Twelve previously reported MprF mutations associated with daptomycin non-susceptibility were identified in 83% of the isolates. Novel MprF mutations identified included P314A, P314F, P314T, S337T, L341V, F349del, and T423R., Conclusions: Daptomycin non-susceptible S. aureus causing infections in Australia are polyclonal and harbour MprF mutation(s). The identification of multidrug-resistant daptomycin non-susceptible S. aureus is a public health concern., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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11. Emergence and clonal expansion of a qacA-harbouring sequence type 45 lineage of methicillin-resistant Staphylococcus aureus.
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Nong Y, Steinig E, Pollock GL, Taiaroa G, Carter GP, Monk IR, Pang S, Daley DA, Coombs GW, Forde BM, Harris PNA, Sherry NL, Howden BP, Pasricha S, Baines SL, and Williamson DA
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- Humans, Staphylococcus aureus genetics, Bayes Theorem, Phylogeny, Membrane Transport Proteins genetics, Bacterial Proteins genetics, Australia, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
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., (© 2024. The Author(s).)
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- 2024
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12. Daptomycin non-susceptible Staphylococcus argenteus isolated from a patient without prior antibiotic exposure.
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Lim C, Mowlaboccus S, Daley DA, Shoby P, and Coombs GW
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- Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Staphylococcus, Microbial Sensitivity Tests, Daptomycin pharmacology, Staphylococcal Infections drug therapy
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- 2024
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13. Corrigendum: Genomic characterisation of a unique Panton-Valentine leucocidin-positive community-associated methicillin-resistant Staphylococcus aureus lineage increasingly impacting Australian indigenous communities.
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Ramsay JP, Parahitiyawa N, Mowlaboccus S, Mullally CA, Yee NWT, Shoby P, Colombi E, Tan HL, Pearson JC, and Coombs GW
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- 2024
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14. Genomic characterization of a unique Panton-Valentine leucocidin-positive community-associated methicillin-resistant Staphylococcus aureus lineage increasingly impacting on Australian indigenous communities.
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Ramsay JP, Parahitiyawa N, Mowlaboccus S, Mullally CA, Yee NWT, Shoby P, Colombi E, Tan HL, Pearson JC, and Coombs GW
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- Australia, Leukocidins genetics, Genomics, Western Australia, Methicillin-Resistant Staphylococcus aureus genetics
- Abstract
In 2010 a single isolate of a trimethoprim-resistant multilocus sequence type 5, Panton-Valentine leucocidin-positive, community-associated methicillin-resistant Staphylococcus aureus (PVL-positive ST5 CA-MRSA), colloquially named WA121, was identified in northern Western Australia (WA). WA121 now accounts for ~14 % of all WA MRSA infections. To gain an understanding of the genetic composition and phylogenomic structure of WA121 isolates we sequenced the genomes of 155 WA121 isolates collected 2010-2021 and present a detailed genomic description. WA121 was revealed to be a single clonally expanding lineage clearly distinct from sequenced ST5 strains reported outside Australia. WA121 strains were typified by the presence of the distinct PVL phage φSa2wa-st5, the recently described methicillin resistance element SCC mec IVo carrying the trimethoprim resistance ( dfrG ) transposon Tn 4791 , the novel β-lactamase transposon Tn 7702 and the epidermal cell differentiation inhibitor (EDIN-A) plasmid p2010-15611-2. We present evidence that SCC mec IVo together with Tn 4791 has horizontally transferred to Staphylococcus argenteus and evidence of intragenomic movement of both Tn 4791 and Tn 7702 . We experimentally demonstrate that p2010-15611-2 is capable of horizontal transfer by conjugative mobilization from one of several WA121 isolates also harbouring a pWBG749-like conjugative plasmid. In summary, WA121 is a distinct and clonally expanding Australian PVL-positive CA-MRSA lineage that is increasingly responsible for infections in indigenous communities in northern and western Australia. WA121 harbours a unique complement of mobile genetic elements and is capable of transferring antimicrobial resistance and virulence determinants to other staphylococci.
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- 2023
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15. Antimicrobial surveillance: A 20-year history of the SMART approach to addressing global antimicrobial resistance into the future.
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Cantón R, Gottlieb T, Coombs GW, Woo PCY, Korman TM, Garcia-Castillo M, Daley D, Bauer KA, Wong M, Wolf DJ, Siddiqui F, and Motyl M
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- Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Drug Resistance, Bacterial
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Antimicrobial resistance (AMR) is a major global public health threat, particularly affecting patients in resource-poor settings. Comprehensive surveillance programmes are essential to reducing the high mortality and morbidity associated with AMR and are integral to informing treatment decisions and guidelines, appraising the effectiveness of intervention strategies, and directing development of new antibacterial agents. Various surveillance programmes exist worldwide, including those administered by government bodies or funded by the pharmaceutical industry. One of the largest and longest running industry-sponsored AMR surveillance programme is the Study for Monitoring Antimicrobial Resistance Trends (SMART), which recently completed its 20th year. The SMART database has grown to almost 500 000 isolates from over 200 sites in more than 60 countries, encompassing all major geographic regions and including many sites in low- and middle-income countries. The SMART surveillance programme has evolved in scope over time, including additional antibacterial agents, pathogens and infection sites, in line with changing epidemiology and medical need. Surveillance data from SMART and similar programmes have been used successfully to detect emerging resistance threats and AMR patterns in specific countries and regions, thus informing national and local clinical treatment guidelines. The SMART database can be accessed readily by physicians and researchers globally, which may be especially valuable to those from countries with limited healthcare resources, where surveillance and resistance data are rarely collected. Continued participation from as many sites as possible worldwide and maintenance of adequate funding are critical factors to fully realising the potential of large-scale AMR surveillance programmes into the future., (Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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16. Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Surveillance Outcome Program (GnSOP) Bloodstream Infection Annual Report 2022.
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Bell JM, Fajardo Lubian A, Partridge SR, Gottlieb T, Robson J, Iredell JR, Daley DA, and Coombs GW
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- Humans, Agar, Escherichia coli, Drug Resistance, Bacterial, Australia epidemiology, Klebsiella pneumoniae, Pseudomonas aeruginosa, Anti-Bacterial Agents pharmacology, Sepsis epidemiology
- Abstract
The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric gram-negative pathogens. The 2022 survey was the tenth year to focus on blood stream infections caused by Enterobacterales, and the eighth year where Pseudomonas aeruginosa and Acinetobacter species were included. Fifty-five hospitals Australia-wide participated in 2022. The 2022 survey tested 9,739 isolates, comprising Enterobacterales (8,773; 90.1%), P. aeruginosa (840; 8.6%) and Acinetobacter species (126; 1.3%), using commercial automated methods. The results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2023). Key resistances included resistance to the third-generation cephalosporin ceftriaxone in 12.7%/12.7% (CLSI/EUCAST criteria) of Escherichia coli and in 6.6%/6.6% of Klebsiella pneumoniae complex. Resistance rates to ciprofloxacin were 13.7%/13.7% for E. coli; 7.8%/7.8% for K. pneumoniae complex; 5.3%/5.3% for Enterobacter cloacae complex; and 4.3%/10.0% for P. aeruginosa. Resistance rates to piperacillin-tazobactam were 2.8%/5.9%; 2.9%/8.7%; 18.3%/27.2%; and 6.1%/14.7% for the same four species, respectively. Twenty-nine Enterobacterales isolates from 28 patients were shown to harbour a carbapenemase gene: 18 blaIMP-4; four blaNDM-5; three blaNDM-1; one blaOXA-181; one blaOXA-244; one blaNDM-1 + blaOXA-181; and one blaNDM-5 + blaOXA-181. Transmissible carbapenemase genes were also detected among two Acinetobacter baumannii complex isolates (blaOXA-23) and one P. aeruginosa (blaNDM-1) in the 2022 survey., (© Commonwealth of Australia CC BY-NC-ND)
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- 2023
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17. Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Surveillance Outcome Program (AESOP) Bloodstream Infection Annual Report 2022.
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Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
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- Humans, Anti-Bacterial Agents pharmacology, Agar, Australia epidemiology, Linezolid, Drug Resistance, Bacterial, Enterococcus, Ampicillin, Daptomycin, Gram-Positive Bacterial Infections epidemiology, Sepsis epidemiology, Bacteremia epidemiology, Anti-Infective Agents pharmacology
- Abstract
From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Enterococcal Surveillance Outcome Program (AESOP). The aim of AESOP 2022 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 1,535 unique episodes of enterococcal bacteraemia investigated, 92.8% were caused by either E. faecalis (52.9%) or E. faecium (39.9%). Ampicillin and vancomycin resistance were not detected in E. faecalis but were detected in 95.4% and 46.9% of E. faecium respectively. One E. faecalis isolate, with a daptomycin minimum inhibitory concentration (MIC) of 8.0 mg/L, harboured the F478L GdpD mutation. One E. faecium with a daptomycin MIC of 24.0 mg/L harboured the A20D Cls mutation; both mutations are known to be associated with daptomycin resistance. Two E. faecium isolates, one with a linezolid MIC ≥ 256 mg/L and the other with a linezolid MIC of 16 mg/L, harboured the 23S rRNA G2576T mutation, a mutation associated with linezolid resistance in enterococci. Overall, 48.8% of E. faecium harboured either the vanA or the vanB gene, of which 28.0% harboured vanA and 72.0% harboured vanB. The percentage of vancomycin-resistant E. faecium bacteraemia isolates in Australia remains substantially higher than that recorded in most European countries. The E. faecium isolates consisted of 62 multi-locus sequence types (STs); 85.5% of isolates were classified into eight major STs each containing ten or more isolates. All major STs belonged to clonal complex (CC) 17, a major hospital-adapted polyclonal E. faecium cluster. The major STs (ST17, ST78, ST80, ST117, ST555, ST796, ST1421, and ST1424) were each found across most regions of Australia. The predominant ST was ST17, which was identified in all regions. Overall, 53.7% of isolates belonging to the eight major STs harboured the vanA or vanB gene. AESOP 2022 has shown that enterococcal bacteraemia episodes in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA- or vanB-positive E. faecium which have limited treatment options., (© Commonwealth of Australia CC BY-NC-ND)
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- 2023
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18. Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2022.
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Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
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- Humans, Staphylococcus aureus, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Agar therapeutic use, Methicillin therapeutic use, Australia epidemiology, Drug Resistance, Bacterial, Erythromycin therapeutic use, Ciprofloxacin therapeutic use, Gentamicins therapeutic use, Tetracycline therapeutic use, Staphylococcal Infections epidemiology, Staphylococcal Infections drug therapy, Methicillin-Resistant Staphylococcus aureus, Bacteremia epidemiology, Cross Infection epidemiology, Cross Infection drug therapy, Anti-Infective Agents
- Abstract
From 1 January to 31 December 2022, fifty-five institutions across Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP). The aim of ASSOP 2022 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 3,214 SAB episodes were reported, of which 77.5% were community-onset. Overall, 15.0% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 21.4%, which was significantly different to the 16.8% all-cause mortality associated with methicillin-susceptible SAB (p = 0.02). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 31% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 13% to tetracycline; 11% to gentamicin; and 2% to co-trimoxazole. One MRSA isolate, with a daptomycin MIC of 1.5 mg/L, harboured the A302V mprF and A23V cls2 mutations. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in one MRSA isolate. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and to the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired resistance to multiple antimicrobials including ciprofloxacin, clindamycin, erythromycin, gentamicin, and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 86% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 72% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST97-IV [2B]; ST953-IV [2B]; and ST8-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia., (© Commonwealth of Australia CC BY-NC-ND)
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- 2023
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19. Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.
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Gordon JP, Al Taie A, Miller RL, Dennis JW, Blaskovich MAT, Iredell JR, Turnidge JD, Coombs GW, Grolman DC, and Youssef J
- Abstract
Introduction: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making., Methods: A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied., Results: Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million., Discussion: Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here., Conclusion: These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials., (© 2023. The Author(s).)
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- 2023
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20. Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number.
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Wagner TM, Janice J, Schulz M, Ballard SA, da Silva AG, Coombs GW, Daley DA, Pang S, Mowlaboccus S, Stinear T, Hegstad K, Howden BP, and Sundsfjord A
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- Humans, Vancomycin pharmacology, Anti-Bacterial Agents pharmacology, DNA Copy Number Variations, Australia epidemiology, Enterococcus genetics, Plasmids genetics, Multigene Family, Bacterial Proteins genetics, Enterococcus faecium genetics, Gram-Positive Bacterial Infections epidemiology
- Abstract
Vancomycin variable enterococci (VVE) are van-positive enterococci with a vancomycin-susceptible phenotype (VVE-S) that can convert to a resistant phenotype (VVE-R) and be selected for during vancomycin exposure. VVE-R outbreaks have been reported in Canada and Scandinavian countries. The aim of this study was to examine the presence of VVE in whole genome sequenced (WGS) Australian bacteremia Enterococcus faecium (Efm) isolates collected through the Australian Group on Antimicrobial resistance (AGAR) network. Eight potential VVEAus isolates, all identified as Efm ST1421, were selected based on the presence of vanA and a vancomycin-susceptible phenotype. During vancomycin selection, two potential VVE-S harboring intact vanHAX genes, but lacking the prototypic vanRS and vanZ genes, reverted to a resistant phenotype (VVEAus-R). Spontaneous VVEAus-R reversion occurred at a frequency of 4-6 × 10
-8 resistant colonies per parent cell in vitro after 48 h and led to high-level vancomycin and teicoplanin resistance. The S to R reversion was associated with a 44-bp deletion in the vanHAX promoter region and an increased vanA plasmid copy number. The deletion in the vanHAX promoter region enables an alternative constitutive promoter for the expression of vanHAX. Acquisition of vancomycin resistance was associated with a low fitness cost compared with the corresponding VVEAus-S isolate. The relative proportion of VVEAus-R vs. VVEAus-S decreased over time in serial passages without vancomycin selection. Efm ST1421 is one of the predominant VanA-Efm multilocus sequence types found across most regions of Australia, and has also been associated with a major prolonged VVE outbreak in Danish hospitals., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)- Published
- 2023
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21. A multi-site, international laboratory study to assess the performance of penicillin susceptibility testing of Staphylococcus aureus.
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Henderson A, Cheng MP, Chew KL, Coombs GW, Davis JS, Grant JM, Gregson D, Giulieri SG, Howden BP, Lee TC, Nguyen V, Mora JM, Morpeth SC, Robinson JO, Tong SYC, and Van Hal SJ
- Subjects
- Humans, Staphylococcus aureus genetics, Penicillins pharmacology, Microbial Sensitivity Tests, Clinical Decision-Making, Uncertainty, Anti-Bacterial Agents pharmacology, Staphylococcal Infections
- Abstract
Objectives: There is clinical uncertainty over the optimal treatment for penicillin-susceptible Staphylococcus aureus (PSSA) infections. Furthermore, there is concern that phenotypic penicillin susceptibility testing methods are not reliably able to detect some blaZ-positive S. aureus., Methods: Nine S. aureus isolates, including six genetically diverse strains harbouring blaZ, were sent in triplicate to 34 participating laboratories from Australia (n = 14), New Zealand (n = 6), Canada (n = 12), Singapore (n = 1) and Israel (n = 1). We used blaZ PCR as the gold standard to assess susceptibility testing performance of CLSI (P10 disc) and EUCAST (P1 disc) methods. Very major errors (VMEs), major error (MEs) and categorical agreement were calculated., Results: Twenty-two laboratories reported 593 results according to CLSI methodology (P10 disc). Nineteen laboratories reported 513 results according to the EUCAST (P1 disc) method. For CLSI laboratories, the categorical agreement and calculated VME and ME rates were 85% (508/593), 21% (84/396) and 1.5% (3/198), respectively. For EUCAST laboratories, the categorical agreement and calculated VME and ME rates were 93% (475/513), 11% (84/396) and 1% (3/198), respectively. Seven laboratories reported results for both methods, with VME rates of 24% for CLSI and 12% for EUCAST., Conclusions: The EUCAST method with a P1 disc resulted in a lower VME rate compared with the CLSI methods with a P10 disc. These results should be considered in the context that among collections of PSSA isolates, as determined by automated MIC testing, less than 10% harbour blaZ. Furthermore, the clinical relevance of phenotypically susceptible, but blaZ-positive S. aureus, remains unclear., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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22. Mycoplasma and Ureaplasma Donor-Derived Infection and Hyperammonemia Syndrome in 4 Solid Organ Transplant Recipients From a Single Donor.
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Wigston C, Lavender M, Long R, Sankhesara D, Ching D, Weaire-Buchanan G, Mowlaboccus S, Coombs GW, Lam K, Wrobel J, Yaw MC, Musk M, and Boan P
- Abstract
Hyperammonemia syndrome (HS) is a life-threatening condition occurring in solid organ transplant patients, affecting primarily lung recipients, and is associated with Mycoplasma hominis and/or Ureaplasma spp infection. The organ donor was a young man who died of hypoxic brain injury and had urethral discharge antemortem. The donor and 4 solid organ transplant recipients had infection with M hominis and/or Ureaplasma spp. The lung and heart recipients both developed altered conscious state and HS associated with M hominis and Ureaplasma spp infections. Despite treatment with antibiotics and ammonia scavengers, both the lung and heart recipients died at day +102 and day +254, respectively. After diagnosis in the thoracic recipients, screening samples from the liver recipient and 1 kidney recipient were culture positive for M hominis with or without Ureaplasma spp. Neither the liver nor kidney recipients developed HS. Our case series demonstrates the unique finding of M hominis and Ureaplasma spp dissemination from an immunocompetent donor across 4 different organ recipients. Phylogenetic whole genome sequencing analysis demonstrated that M hominis samples from recipients and donor were closely related, suggesting donor-derived infection. Screening of lung donors and/or recipients for Mycoplasma and Ureaplasma spp is recommended, as well as prompt treatment with antimicrobials to prevent morbidity., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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23. Genomic characterisation of linezolid-resistant Enterococcus faecalis from Western Australia 2016-2021.
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Mowlaboccus S, Daley DA, and Coombs GW
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- Humans, Linezolid pharmacology, Enterococcus faecalis genetics, Western Australia epidemiology, Anti-Bacterial Agents pharmacology, Enterococcus, Genomics, Microbial Sensitivity Tests, Drug Resistance, Bacterial genetics, Gram-Positive Bacterial Infections drug therapy, Gram-Positive Bacterial Infections epidemiology, Enterococcus faecium
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- 2023
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24. Travel-associated lineages and unique endemic antimicrobial-susceptible lineages of Neisseria gonorrhoeae predominate in Western Australia.
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Al Suwayyid BA, Haese EC, Mowlaboccus S, Pearson JC, Whiley DM, Armstrong PK, Giele CM, Mak DB, Bastian L, Wise MJ, Coombs GW, and Kahler CM
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- Humans, Neisseria gonorrhoeae, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Azithromycin pharmacology, Multilocus Sequence Typing, Western Australia epidemiology, Bayes Theorem, Travel, Molecular Epidemiology, Gonorrhea epidemiology, Gonorrhea drug therapy, Anti-Infective Agents
- Abstract
In Australia, gonococcal isolates are monitored for antimicrobial susceptibilities. In Western Australia (WA), gonorrhoea notification rates increased by 63 % between 2013 and 2016, with the steepest increase occurring between 2015 and 2016, before stabilizing at this higher baseline between 2017 and 2020. This increased prevalence was associated with antimicrobial-susceptible (AMS) lineages. To understand the provenance of these isolates causing gonorrhoea in WA, whether they were introduced or expanded from endogenous lineages, 741 isolates were collected in 2017 and characterized by both iPLEX typing and whole genome sequencing (WGS). Antibiograms and genocoding of the isolates revealed that AMS isolates were most prevalent in the remote regions, while the urban/rural regions were characterized by antimicrobial-resistant (AMR) isolates. iPLEX typing identified 78 iPLEX genotypes (WA-1 to WA-78) of which 20 accounted for over 88 % of isolates. WA-10 was the most frequently identified genotype in the urban/rural regions whilst WA-29 was the most frequently identified genotype in the remote regions. Genotypes WA-38, WA-52 and WA-13 accounted for 81 % ( n =36/44) of the azithromycin-resistant N. gonorrhoeae (AziR) isolates. A representative isolate of each iPLEX genotype and AMR biotype was whole genome sequenced and analysed using MLST, NG-MAST and NG-STAR, and the novel core genome clustering Ng_cgc_400 typing scheme. Five predominant Bayesian population groups (termed BPG-1 to 5) were identified in the study collection. BPG-1 and BPG-2 were associated with AMS isolates from the remote regions. BPG-1 and BPG-2 were shown to be unique to the remote regions based on a minimum spanning tree against 4000 international isolates. AMS isolates in urban/rural regions were dominated by international lineages. AziR and Cef DS (decreased susceptibility to ceftriaxone) was concentrated in three urban/rural genomic groups (BPG-3, 4 and 5). Azithromycin minimum inhibitory concentrations (0.5-16 mg l
-1 ) correlated with the accumulation of mtrR mutations or/and the fraction of 23S rRNA C2611T mutated copies. The majority of isolates in BPG-3, 4 and 5 could be correlated with known AMR lineages circulating globally and nationally. In conclusion, the surge in AMS isolates in WA in 2017 was due to importation of international AMS lineages into urban/rural regions, whilst the local AMS lineages persisted largely in the remote regions. Bridging between the urban/rural and remote regions was relatively rare, but continued surveillance is required to prevent ingress of AMR strains/lineages into the remote regions of WA.- Published
- 2023
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25. Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP).
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Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
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- Humans, Staphylococcus aureus, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Agar therapeutic use, Australia epidemiology, Methicillin therapeutic use, Microbial Sensitivity Tests, Drug Resistance, Bacterial, Gentamicins therapeutic use, Erythromycin therapeutic use, Ciprofloxacin therapeutic use, Tetracycline therapeutic use, Staphylococcal Infections epidemiology, Staphylococcal Infections drug therapy, Methicillin-Resistant Staphylococcus aureus, Bacteremia epidemiology, Cross Infection drug therapy, Anti-Infective Agents
- Abstract
Abstract: From 1 January to 31 December 2021, forty-eight institutions around Australia participated in the Australian Staphylococcus aureus Surveillance Outcome Programme (ASSOP). The aim of ASSOP 2021 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterisation of the molecular epidemiology of the methicillin-resistant isolates. A total of 2,928 SAB episodes were reported, of which 78.4% were community-onset. Overall, 16.9% of S. aureus isolates were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 15.0%, which was not significantly different from the 14.4% all-cause mortality associated with methicillin-susceptible SAB (p = 0.7). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 36% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin; 30% to erythromycin; 15% to tetracycline; 16% to gentamicin; and 3% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in three S. aureus isolates. Resistance to vancomycin or linezolid was not detected. Resistance to non-β-lactam antimicrobials was largely attributable to the healthcare-associated MRSA (HA-MRSA) clone ST22-IV [2B] (EMRSA-15), and the community-associated MRSA (CA-MRSA) clone ST45-V [5C2&5] which has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. Nonetheless, 85% of methicillin-resistant SAB episodes were due to CA-MRSA clones. Although polyclonal, approximately 68% of CA-MRSA clones were characterised as ST93-IV [2B] (Queensland clone); ST45-V [5C2&5]; ST5-IV [2B]; ST1-IV [2B]; ST30-IV [2B]; and ST97-IV [2B]. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus bacteraemia., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2022
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26. Molecular confirmation of Escherichia coli classified as fosfomycin-resistant by the revised EUCAST MIC breakpoint.
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Mowlaboccus S, Daley DA, Shoby P, and Coombs GW
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- Humans, Escherichia coli genetics, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Fosfomycin pharmacology, Escherichia coli Infections drug therapy
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- 2022
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27. Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Surveillance Outcome Program (GnSOP).
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Bell JM, Lubian AF, Partridge SR, Gottlieb T, Robson J, Iredell JR, Daley DA, and Coombs GW
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- Humans, Australia epidemiology, Microbial Sensitivity Tests, Agar, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial
- Abstract
Abstract: The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric gram-negative pathogens. The 2021 survey was the ninth year to focus on bloodstream infections caused by Enterobacterales, and the seventh year where Pseudomonas aeruginosa and Acinetobacter species were included. The 2021 survey tested 8,947 isolates, comprising Enterobacterales (8,104; 90.6%), P. aeruginosa (745; 8.3%) and Acinetobacter species (98; 1.1%), using commercial automated methods. The results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2022). Of the key resistances, resistance to the third-generation cephalosporin ceftriaxone was found in 12.5%/12.5% (CLSI/EUCAST criteria) of Escherichia coli and in 6.1%/6.1% of Klebsiella pneumoniae. Resistance rates to ciprofloxacin were 12.3%/12.3% for E. coli; 7.2%/7.2% for K. pneumoniae; 5.4%/5.4% for Enterobacter cloacae complex; and 3.7%/8.0% for P. aeruginosa. Resistance rates to piperacillin-tazobactam were 2.8%/6.5%; 2.9%/9.9%; 18.4%/28.1%; and 6.9%/12.8% for the same four species, respectively. Seventeen Enterobacterales isolates from 17 patients were shown to harbour a carbapenemase gene: 12 blaIMP-4; two blaNDM-7; one blaNDM-1; one blaOXA-181; and one blaKPC-2. No transmissible carbapenemase genes were detected among P. aeruginosa or Acinetobacter isolates in the 2021 survey., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2022
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28. Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Surveillance Outcome Program (AESOP).
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Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
- Subjects
- Humans, Anti-Bacterial Agents pharmacology, Agar, Vancomycin, Microbial Sensitivity Tests, Drug Resistance, Bacterial, Enterococcus genetics, Northern Territory, Gram-Positive Bacterial Infections epidemiology, COVID-19, Bacteremia epidemiology
- Abstract
Abstract: From 1 January to 31 December 2021, forty-eight institutions around Australia participated in the Australian Enterococcal Surveillance Outcome Programme (AESOP). The aim of AESOP 2021 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the Enterococcus faecium isolates. Of the 1,297 unique episodes of enterococcal bacteraemia investigated, 94.4% were caused by either E. faecalis (54.1%) or E. faecium (40.3%). Ampicillin resistance was detected in one E. faecalis isolate and in 89.3% of E. faecium isolates. Vancomycin non-susceptibility was not detected in E. faecalis but was detected in 37.9% of E. faecium. Overall, 39.6% of E. faecium harboured the vanA and/or vanB genes. For the vanA/vanB positive E. faecium isolates, 35.8% harboured the vanA gene and 64.2% the vanB gene. Although the percentage of vancomycin-resistant E. faecium bacteraemia isolates was significantly lower than that reported in the 2020 AESOP report (presumably due to the COVID-19 elective surgery restrictions placed on hospitals), it remains substantially higher than that recorded in most European countries. Isolates of E. faecium consisted of 73 multi-locus sequence types (STs); 77.2% of isolates were classified into seven major STs each containing more than ten isolates. All major STs belonged to clonal cluster (CC) 17, a major hospital-adapted polyclonal E. faecium cluster. The major STs (ST17, ST1424, ST796, ST78, ST80, ST1421 and ST555) were found across most regions of Australia. The predominant ST was ST17 which was identified in all regions except the Northern Territory. Overall, 46.5% of isolates belonging to the seven major STs harboured the vanA or vanB gene. The AESOP 2021 has shown that enterococcal bacteraemia episodes in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin resistant vanA- or vanB-positive E. faecium which have limited treatment options., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2022
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29. Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.
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Coombs GW, Yee NWT, Daley D, Bennett CM, Robinson JO, Stegger M, Shoby P, and Mowlaboccus S
- Abstract
Background: Defined by the emergence of antibiotic resistant strains, Staphylococcus aureus is a priority bacterial species with high antibiotic resistance. However, a rise in the prevalence of penicillin-susceptible S. aureus (PSSA) bloodstream infections has recently been observed worldwide, including in Australia, where the proportion of methicillin-susceptible S. aureus causing bacteremia identified phenotypically as penicillin-susceptible has increased by over 35%, from 17.5% in 2013 to 23.7% in 2020., Objectives: To determine the population structure of PSSA causing community- and hospital-onset bacteremia in Australia and to evaluate routine phenotypic antimicrobial susceptibility methods to reliably confirm penicillin resistance on blaZ -positive S. aureus initially classified as penicillin-susceptible by the Vitek
® 2 automated microbiology system., Results: Whole genome sequencing on 470 PSSA collected in the 2020 Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme identified 84 multilocus sequence types (STs), of which 79 (463 isolates) were grouped into 22 clonal complexes (CCs). The dominant CCs included CC5 (31.9%), CC97 (10.2%), CC45 (10.0%), CC15 (8.7%), and CC188 (4.9%). Many of the CCs had multiple STs and spa types and, based on the immune evasion cluster type, isolates within a CC could be classified into different strains harboring a range of virulence and resistance genes. Phylogenetic analyses of the isolates showed most CCs were represented by one clade. The blaZ gene was identified in 45 (9.6%) PSSA. Although multiclonal, approximately 50% of blaZ -positive PSSA were from CC15 and were found to be genetically distant from the blaZ -negative CC15 PSSA. The broth microdilution, Etest® and cefinase, performed poorly; however, when the appearance of the zone edge was considered; as per the EUCAST and CLSI criteria, disc diffusion detected 100% of blaZ -positive PSSA., Conclusions: In Australia, PSSA bacteremia is not caused by the expansion of a single clone. Approximately 10% of S. aureus classified as penicillin-susceptible by the Vitek® 2 harbored blaZ . Consequently, we recommend that confirmation of Vitek® 2 PSSA be performed using an alternative method, such as disc diffusion with careful interpretation of the zone edge.- Published
- 2022
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30. Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.
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Campbell AJ, Mowlaboccus S, Coombs GW, Daley DA, Al Yazidi LS, Phuong LK, Leung C, Best EJ, Webb RH, Voss L, Athan E, Britton PN, Bryant PA, Butters CT, Carapetis JR, Ching NS, Francis J, Hung TY, Nourse C, Ojaimi S, Tai A, Vasilunas N, McMullan B, Bowen AC, and Blyth CC
- Subjects
- Australia epidemiology, Child, Humans, Molecular Epidemiology, Prospective Studies, Staphylococcus aureus, Whole Genome Sequencing, Bacteremia epidemiology, Bacteremia microbiology, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
- Abstract
Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration., Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort., Results: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2])., Conclusion: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management., Competing Interests: Declaration of Competing Interest P.A.B. reports grants from National Health and Medical Research Council, Medical Research Futures Fund and Murdoch Children's Research Institute outside the submitted work and travel funds from the Royal Children's Hospital. S.O. has acted on an advisory board for CSL-Behring. All remaining authors have no reported conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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31. Genomic characterisation of CC398 MRSA causing severe disease in Australia.
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Coombs GW, Daley D, Shoby P, Yee NWT, Robinson JO, Murray R, Korman TM, Warner MS, Papanaoum K, Derrington P, Horvath R, Jenney A, Spelman D, and Mowlaboccus S
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Australia epidemiology, Genomics, Livestock, Phylogeny, Staphylococcus aureus genetics, Bacteremia drug therapy, Bacteremia epidemiology, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections drug therapy, Staphylococcal Infections epidemiology
- Abstract
Clonal complex 398 (CC398) livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been reported worldwide in a variety of food-animal species. Although CC398 is synonymous with LA-MRSA, community-associated MRSA (CA-MRSA) variants have emerged, including the Panton-Valentine leukocidin (PVL)-positive ST398-V and ST398 single-locus variant ST1232-V, and the PVL-negative ST398-V clones. Using comparative genomic analysis, we determined whether ten CC398 MRSA bacteraemia episodes recently identified in Australia were due to LA-MRSA or CA-MRSA CC398. Isolates were sourced from the Australian Group on Antimicrobial Resistance S. aureus surveillance programme and episodes occurred across Australia. Whole-genome sequencing (WGS) and phylogenetic comparison of the ten CC398 bacteraemia isolates with previously published CC398 MRSA whole-genome sequences identified that the Australian CC398 isolates were closely related to the human-associated II-GOI clade and the livestock-associated IIa clade. The identified CC398 MRSA clones were: PVL-positive ST1232-V (5C2&5), PVL-negative community-associated ST398-V (5C2&5) and livestock-associated ST398-V (5C2&5). Our findings demonstrate the importance of using WGS and comparing the sequences with international sequences to distinguish between CC398 CA-MRSA and LA-MRSA and to determine the isolates' origin. Furthermore, our findings suggest that CC398 CA-MRSA has become established in the Australian community and that ST398-V (5C2&5) LA-MRSA is now widespread in Australian piggeries. Our study emphasises the need for national One Health antimicrobial resistance surveillance programmes to assist in monitoring the ongoing epidemiology of MRSA and other clinically significant antimicrobial-resistant organisms., (Copyright © 2022. Published by Elsevier Ltd.)
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- 2022
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32. Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome.
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Campbell AJ, Al Yazidi LS, Phuong LK, Leung C, Best EJ, Webb RH, Voss L, Athan E, Britton PN, Bryant PA, Butters CT, Carapetis JR, Ching NS, Coombs GW, Daley DA, Francis JR, Hung TY, Mowlaboccus S, Nourse C, Ojaimi S, Tai A, Vasilunas N, McMullan B, Blyth CC, and Bowen AC
- Subjects
- Anti-Bacterial Agents therapeutic use, Child, Cross-Sectional Studies, Humans, Infant, Newborn, Prospective Studies, Retrospective Studies, Staphylococcus aureus, Bacteremia drug therapy, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections drug therapy, Staphylococcal Infections epidemiology
- Abstract
Background: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood., Methods: ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017-2018)., Results: Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6-296.9), multifocal infection (aOR, 22.6; CI, 1.4-498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7-1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1-268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6-434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI .004-.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3-8.1)., Conclusions: High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2022
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33. Apophysomyces Variabilis Infection in Transplant Recipients due to Unrecognized Infection in an Intravenous Drug-Using Donor.
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Boan P, Pang S, Mowlaboccus S, Wrobel JP, Musk M, Lavender M, Yaw MC, Hernest A, MacQuillan G, Dembo LG, Coombs GW, Gardam DJ, Pereira LA, and Robinson JO
- Subjects
- Humans, Tissue Donors, Transplant Recipients, Mucorales, Mucormycosis diagnosis, Mucormycosis drug therapy, Mucormycosis etiology
- Abstract
Competing Interests: The authors declare no conflicts of interest.
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- 2022
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34. The changing molecular epidemiology of Enterococcus faecium harbouring the van operon at a teaching hospital in Western Australia: A fifteen-year retrospective study.
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Lee T, Pang S, Daley DA, Pearson JC, Abraham S, and Coombs GW
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- Anti-Bacterial Agents, Hospitals, Teaching, Humans, Microbial Sensitivity Tests, Molecular Epidemiology, Operon, Phylogeny, Retrospective Studies, Western Australia, Enterococcus faecium genetics, Gram-Positive Bacterial Infections
- Abstract
Introduction: Enterococcus faecium is an opportunistic pathogen that has become one of the leading causes of hospital acquired infection that are resistant to multiple critically important antimicrobials., Aim: The objective of the study was to describe the molecular characteristics and relationship between major strains of E. faecium harbouring the van operon and to determine if the strains had increasing virulence and antimicrobial resistance determinants over time., Methods: E. faecium harbouring the van operon detected using PCR from surveillance rectal swabs of patients that were admitted to high-risk units at a Perth teaching hospital from 2001 to 2015 were retrospectively analysed using a whole genome sequencing and bioinformatics approach., Results: ST18, ST78, ST80, ST173, ST203 and ST555 were identified as the major STs accounting for 93.7% of E. faecium isolates. Except for ST173, major STs identified at Royal Perth Hospital (RPH) have been reported across Australia and internationally. Isolates from each ST formed independently branched phylogenetic clusters with each harbouring unique virulence and antimicrobial resistance profiles. Depending on the ST, different genes conferring resistance to similar antimicrobial classes were identified. Except for ST80 which harboured the vanA type operon, all major strains harboured the vanB operon conferring only vancomycin resistance., Conclusion: Major strains of E. faecium isolated over 15-years showed unique virulome and resistome profiles with no indication of increasing virulence or antimicrobial resistance determinants. Strains were distantly related and the acquisition of different genes encoding similar antimicrobial resistances suggest the independent evolution of each strain., Data Summary: The whole genome sequences of all isolates from this study are accessible from the NCBI-SRA database under project number PRJNA575940 and PRJNA524213. Published reference sequence Aus0004 was obtained from NCBI-SRA under project number PRJNA86649 DOI:10.1128/JB.00259-12., (Crown Copyright © 2021. Published by Elsevier GmbH. All rights reserved.)
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- 2022
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35. Complete Genome Sequences of Three of the Earliest Community-Associated Methicillin-Resistant Staphylococcus aureus Strains Isolated in Remote Western Australia.
- Author
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Karakatsanis NM, Colombi E, Mowlaboccus S, Pearson JC, Coombs GW, and Ramsay JP
- Abstract
Initially reported in Western Australia in the 1980s, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major cause of S. aureus infections globally. We report the complete genome sequences of three of the earliest CA-MRSA strains isolated from remote Australian Indigenous communities in the Kimberley region of Western Australia.
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- 2021
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36. Complete Genome Sequence of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 1, SCC mec IV[2B], Isolated in the 1990s from Northern Western Australia.
- Author
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Karakatsanis NM, Mowlaboccus S, Colombi E, Pearson JC, Ramsay JP, and Coombs GW
- Abstract
Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) SCC mec IV[2B] has become one of the most common community-associated MRSA clones in Australia. We report the complete genome sequence of one of the earliest isolated Australian S. aureus ST1-MRSA-IV strains, WBG8287, isolated from an Indigenous Australian patient living in the remote Kimberley region of Western Australia.
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- 2021
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37. Molecular characterization of fosfomycin-resistant Escherichia coli urinary tract infection isolates from Australia.
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Mowlaboccus S, Daley DA, Birdsall J, Gottlieb T, Merlino J, Nimmo GR, George N, Korman T, Streitberg R, Robson J, Peachey G, Collignon P, Bradbury S, Rogers BA, and Coombs GW
- Subjects
- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Australia epidemiology, Humans, Microbial Sensitivity Tests, beta-Lactamases, Drug Resistance, Bacterial, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli Infections drug therapy, Escherichia coli Infections epidemiology, Fosfomycin pharmacology, Urinary Tract Infections drug therapy, Urinary Tract Infections epidemiology
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- 2021
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38. Genome-wide association studies reveal candidate genes associated to bacteraemia caused by ST93-IV CA-MRSA.
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Pang S, Daley DA, Sahibzada S, Mowlaboccus S, Stegger M, and Coombs GW
- Subjects
- Australia, Genome-Wide Association Study, Humans, Bacteremia, Community-Acquired Infections, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections genetics
- Abstract
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.
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- 2021
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39. Antimicrobial Resistance in Porcine Enterococci in Australia and the Ramifications for Human Health.
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Lee T, Jordan D, Sahibzada S, Abraham R, Pang S, Coombs GW, O'Dea M, and Abraham S
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- Animals, Australia, Chickens microbiology, Enterococcus genetics, Enterococcus isolation & purification, Environmental Monitoring, Genome, Bacterial, Humans, Microbial Sensitivity Tests, Sepsis microbiology, Swine, Anti-Bacterial Agents pharmacology, Cecum microbiology, Drug Resistance, Bacterial genetics, Enterococcus drug effects
- Abstract
Enterococci are ubiquitous opportunistic pathogens that have become a major public health issue globally. The increasing prevalence of antimicrobial resistance in hospital-adapted enterococci had been thought to originate from livestock. However, this association between livestock and hospital-adapted enterococci is currently unclear. This study investigates the antimicrobial susceptibilities of enterococci isolated from pig cecal samples and compares the genomic characteristics of Enterococcus faecium from pigs to those of isolates from meat chickens and from human sepsis cases. From 200 cecal samples, antimicrobial susceptibility testing was performed for E. faecium ( n = 84), E. hirae ( n = 36), and E. faecalis ( n = 17). Whole-genome sequencing was performed for all E. faecium isolates, and the sequences were compared to those of previously studied isolates from meat chickens and human sepsis cases through bioinformatics analysis. Resistance (non-wild type) to erythromycin, gentamicin, tetracycline, ampicillin, daptomycin, virginiamycin, and quinupristin-dalfopristin was identified. More importantly, except for a single isolate harboring the vanC operon, no resistance was observed in the three species to vancomycin, teicoplanin, and linezolid, which are critically important antimicrobials used to treat enterococcal infections in humans. The E. faecium isolates from chickens were genetically distinct from human and pig isolates, which were more closely related. Human strains that were closely related to pig strains were not typical "hospital-adapted strains" as previously identified. The results of this study show that enterococci from Australian finisher pigs are not a source of resistance to critically important antimicrobials and that E. faecium from pigs is not part of the current human hospital-adapted population. IMPORTANCE Resistance to the critically important antimicrobials vancomycin, teicoplanin, and linezolid is not found in enterococci collected from Australian finisher pigs. However, some antimicrobial resistance was observed. In particular, resistance to quinupristin-dalfopristin, a combination of two streptogramin class antimicrobials, was identified despite the absence of streptogramin use Australia-wide since 2005. Other observed resistance among enterococci from pigs include chloramphenicol, erythromycin, and tetracycline resistance. Genomic comparison of E. faecium from Australian pigs to isolates collected from previous studies on chickens and humans indicate that E. faecium from pigs are genetically more similar to those of humans than those from chickens. Despite the increased genetic similarities, E. faecium strains from pigs are phylogenetically distinct and did not belong to the dominant sequence types found in hospital-adapted strains causing sepsis in humans. Therefore, the results indicate that Australian finisher pigs are not a source of hospital-adapted E. faecium in Australia., (Copyright © 2021 American Society for Microbiology.)
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- 2021
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40. Global Epidemiology and Evolutionary History of Staphylococcus aureus ST45.
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Effelsberg N, Stegger M, Peitzmann L, Altinok O, Coombs GW, Pichon B, Kearns A, Randad PR, Heaney CD, Bletz S, Schaumburg F, and Mellmann A
- Subjects
- Australia epidemiology, Bayes Theorem, Europe epidemiology, Humans, Phylogeny, Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
Staphylococcus aureus ST45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. It is one of the most prevalent carrier lineages but also frequently causes severe invasive disease, such as bacteremia. Little is known about its evolutionary history. In this study, we used whole-genome sequencing to analyze a large collection of 451 diverse ST45 isolates from 6 continents and 26 countries. De novo -assembled genomes were used to understand genomic plasticity and to perform coalescent analyses. The ST45 population contained two distinct sublineages, which correlated with the isolates' geographical origins. One sublineage primarily consisted of European/North American isolates, while the second sublineage primarily consisted of African and Australian isolates. Bayesian analysis predicted ST45 originated in northwestern Europe about 500 years ago. Isolation time, host, and clinical symptoms did not correlate with phylogenetic groups. Our phylogenetic analyses suggest multiple acquisitions of the SCC mec element and key virulence factors throughout the evolution of the ST45 lineage., (Copyright © 2020 American Society for Microbiology.)
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- 2020
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41. Antimicrobial resistance and genomic insights into bovine mastitis-associated Staphylococcus aureus in Australia.
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O'Dea M, Abraham RJ, Sahibzada S, Lee T, Jordan D, Laird T, Pang S, Buller N, Stegger M, Coombs GW, Trott DJ, and Abraham S
- Subjects
- Animals, Australia epidemiology, Bacterial Typing Techniques, Cattle, Female, Genomics, Humans, Mastitis, Bovine epidemiology, Microbial Sensitivity Tests, Multilocus Sequence Typing, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology, Staphylococcus aureus classification, Virulence Factors genetics, Whole Genome Sequencing, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Mastitis, Bovine microbiology, Staphylococcal Infections veterinary, Staphylococcus aureus drug effects, Staphylococcus aureus genetics
- Abstract
The aim of this study was to investigate antimicrobial resistance and population structure of bovine mastitis-associated Staphylococcus aureus isolates, and compare them to human isolates obtained from Western Australian hospitals and overseas strains to determine relatedness to human isolates from a zoonotic or reverse zoonotic aspect. Antimicrobial susceptibility testing was performed on 202 S. aureus isolates of which 166 isolates underwent whole genome sequencing. Only resistance to penicillin (12.4%) and erythromycin (0.5%) was identified and of note, no resistance was demonstrated to oxacillin. Genomic characterisation identified 14 multilocus sequence types (STs), with most isolates belonging to clonal complexes 97, 705, and 1. Four distinct clades based on virulence gene composition were identified. The four clades were predominantly ST based, consisting of ST352, ST97, ST81/ST1, and ST705. Core genome comparison of the bovine and human S. aureus isolates demonstrated defined clustering by ST, with the Australian bovine S. aureus isolates clustering together according to their ST separately from human isolates. In addition, a bovine specific cluster comprising Australian ST151 and ST705 isolates, and ST151 isolates from Irish dairy cattle was clearly delineated. Examination of a detailed ST352 phylogeny provided evidence for geographical clustering of Australian strains into a distinct grouping separate from international strains. This study has identified Australian S. aureus isolates have limited genetic diversity and are genetically distinct from human and international bovine S. aureus isolates. Current first line therapies for bovine mastitis in Australian dairy cattle remain appropriate., (Copyright © 2020 Elsevier B.V. All rights reserved.)
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- 2020
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42. Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Sepsis Outcome Programme (GNSOP) Annual Report 2018.
- Author
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Bell JM, Gottlieb T, Daley DA, and Coombs GW
- Subjects
- Australia epidemiology, Gram-Negative Bacterial Infections drug therapy, Humans, Population Surveillance, Treatment Outcome, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria drug effects, Gram-Negative Bacterial Infections epidemiology, Sepsis drug therapy, Sepsis epidemiology
- Abstract
The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric gram-negative pathogens. The 2018 survey was the sixth year to focus on bloodstream infections, and included Enterobacterales, Pseudomonas aeruginosa and Acinetobacter species. Eight thousand three hundred and fifty isolates, comprising Enterobacterales (7,512, 90.0%), P. aeruginosa (743, 8.9%) and Acinetobacter species (95, 1.1%), were tested using commercial automated methods. The results were analysed using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2019). Of the key resistances, resistance to the third-generation cephalosporin, ceftriaxone, was found in 13.4%/13.4% of Escherichia coli (CLSI/EUCAST criteria), and 9.4%/9.4% of Klebsiella pneumoniae . Resistance rates to ciprofloxacin were 15.2%/15.2% for E. coli , 11.3%/11.3% for K. pneumoniae , 7.4%/7.4% for Enterobacter cloacae complex, and 3.6%/7.7% for P. aeruginosa . Resistance rates to piperacillin-tazobactam were 3.0%/6.0%, 4.3%/7.9%, 18.2%/22.0%, and 5.1%/11.1% for the same four species respectively. Thirty-one isolates from 27 patients were shown to harbour a carbapenemase gene: 14 bla
IMP-4 (11 patients), including one with blaIMP-4 + blaOXA-23 , four blaKPC (three patients), three blaOXA-48 , three blaNDM , three blaGES , two blaOXA-181 , and two blaOXA-23 ., (© Commonwealth of Australia CC BY-NC-ND.)- Published
- 2020
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43. Identification and characterisation of fosfomycin resistance in Escherichia coli urinary tract infection isolates from Australia.
- Author
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Mowlaboccus S, Daley D, Pang S, Gottlieb T, Merlino J, Nimmo GR, George N, Korman TM, Streitberg R, Robson J, Peachey G, Collignon P, Bradbury S, Colombi E, Ramsay JP, Rogers BA, and Coombs GW
- Subjects
- Australia, Child, Cross-Sectional Studies, Drug Resistance, Multiple, Bacterial genetics, Escherichia coli genetics, Escherichia coli isolation & purification, Female, Genome, Bacterial, Humans, Microbial Sensitivity Tests, Plasmids genetics, Urinary Tract Infections microbiology, Whole Genome Sequencing, Anti-Bacterial Agents therapeutic use, Escherichia coli drug effects, Escherichia coli Infections drug therapy, Fosfomycin therapeutic use, Urinary Tract Infections drug therapy
- Abstract
Of 1033 Escherichia coli urinary tract infection isolates collected from females >12 years of age in Australia in 2019, only 2 isolates were resistant to fosfomycin with a minimum inhibitory concentration (MIC) of >256 mg/L. Despite having different multilocus sequence types, the two isolates harboured an identical plasmid-encoded fosA4 gene. The fosA4 gene has previously been identified in a single clinical E. coli isolate cultured in Japan in 2014. Each fosfomycin-resistant isolate harboured two conjugative plasmids that possessed an array of genes conferring resistance to aminoglycosides, β-lactams, macrolides, quinolones, sulfonamides and/or trimethoprim., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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44. Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2019.
- Author
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Coombs GW, Daley DA, Mowlaboccus S, and Pang S
- Subjects
- Anti-Bacterial Agents therapeutic use, Australia epidemiology, Bacteremia epidemiology, Bacteremia microbiology, Humans, Population Surveillance, Sepsis microbiology, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Treatment Outcome, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial, Sepsis drug therapy, Sepsis epidemiology, Staphylococcal Infections epidemiology, Staphylococcus aureus drug effects
- Abstract
From 1 January to 31 December 2019, 39 institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2019 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and on characterising the molecular epidemiology of the methicillin-resistant isolates. A total of 3,157 S. aureus bacteraemia episodes were reported, of which 79.8% were community-onset. 18.5% of S. aureus were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 14.0%, which was not significantly different from the 14.3% mortality associated with methicillin-susceptible SAB (p = 0.9). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 36% of methicillin-resistant S. aureus (MRSA) were resistant to ciprofloxacin, 34% to erythromycin, 13% to tetracycline, 9% to gentamicin and 4% to co-trimoxazole. When applying the EUCAST breakpoints, teicoplanin resistance was detected in two S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) is the predominant healthcare-associated clone in Australia. Eighty percent of methicillin-resistant SAB, however, were due to community-associated clones. Although polyclonal, approximately 71.4% of community-associated clones were variously characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-V
T [5C2&5], ST1-IV [2B], ST30-IV [2B], ST78-IV [2B] and ST8-IV [2B]. Community-associated MRSA (CA-MRSA), in particular the ST45-VT [5C2&5] clone, have acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The multiresistant ST45-VT [5C2&5] clone accounted for 12.7% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important that antimicrobial resistance patterns in community- and healthcare-associated SAB are monitored, as this information will guide therapeutic practices in treating S. aureus sepsis., (© Commonwealth of Australia CC BY-NC-ND.)- Published
- 2020
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45. Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Sepsis Outcome Programme (AESOP) Annual Report 2019.
- Author
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Coombs GW, Daley DA, Mowlaboccus S, and Pang S
- Subjects
- Australia epidemiology, Drug Resistance, Multiple, Bacterial, Gram-Positive Bacterial Infections epidemiology, Humans, Population Surveillance, Anti-Bacterial Agents pharmacology, Enterococcus drug effects, Gram-Positive Bacterial Infections microbiology
- Abstract
From 1 January to 31 December 2019, thirty-nine institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2019 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to characterise the molecular epidemiology of the E. faecium isolates. Of the 1,361 unique episodes of bacteraemia investigated, 95.2% were caused by either E. faecalis (51.4%) or E. faecium (43.8%). Ampicillin resistance was not detected in E. faecalis but was detected in 91.1% of E. faecium . Vancomycin non-susceptibility was detected in 0.1% of E. faecalis and in 41.8% of E. faecium . Overall, 45.4% of E. faecium harboured vanA and/or vanB genes. For the vanA / vanB positive E. faecium isolates, 49.1% harboured vanA genes only and 50.6% vanB genes; 0.3% harboured both vanA and vanB genes. The percentage of E. faecium bacteraemia isolates resistant to vancomycin in Australia is substantially higher than that seen in most European countries. E. faecium consisted of 78 multilocus sequence types (STs), of which 75.0% of isolates were classified into six major STs containing ten or more isolates. All major STs belong to clonal cluster (CC) 17, a major hospital-adapted polyclonal E. faecium cluster. The predominant STs (ST1424, ST17, ST796, ST80, ST1421, and ST78) were found across most regions of Australia. The most prevalent clone was ST1424, which was identified in all regions except the Northern Territory and Western Australia. Overall, 51.4% of isolates belonging to the six predominant STs harboured vanA or vanB genes. In 2019, AESOP has shown that enterococcal bacteraemias in Australia are frequently caused by polyclonal ampicillin-resistant high-level gentamicin-resistant vanA or vanB E. faecium which have limited treatment options., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2020
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46. Evaluation of the Haemophilus influenzae EUCAST and CLSI disc diffusion methods to recognize aminopenicillin and amoxicillin/clavulanate resistance.
- Author
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Fernando SA, Pang S, McKew GL, Phan T, Merlino J, Coombs GW, and Gottlieb T
- Subjects
- Amoxicillin-Potassium Clavulanate Combination pharmacology, Anti-Bacterial Agents pharmacology, Australia, Humans, Microbial Sensitivity Tests, beta-Lactamases genetics, Haemophilus Infections, Haemophilus influenzae genetics
- Abstract
Objectives: Implementation of EUCAST susceptibility testing in an Australian hospital laboratory demonstrated higher rates of aminopenicillin and amoxicillin/clavulanate resistance in Haemophilus influenzae than previously recognized. This study aimed to better define the variability in the detection of β-lactam resistance based on EUCAST and CLSI disc diffusion (DD) methodology, by comparison with the recommended reference method, broth microdilution (BMD), and by concordance with genomic analysis., Methods: A total of 100 random H. influenzae isolates were assessed for ampicillin and amoxicillin/clavulanate susceptibility by EUCAST and CLSI DD and BMD. WGS was used to analyse the ftsI gene of a subset of isolates with β-lactam resistance, other than that due to isolated β-lactamase production., Results: Of the 100 isolates, 32 were categorized as either β-lactamase negative, ampicillin resistant (BLNAR) (n = 18) or β-lactamase positive, amoxicillin/clavulanate resistant (BLPACR) (n = 14) by EUCAST DD. All 18 EUCAST BLNAR isolates were genotypically confirmed by WGS. Five of 18 BLNAR isolates were concordant by CLSI DD, 12 by EUCAST BMD and 4 by CLSI BMD. Nine of 14 EUCAST BLPACR isolates were confirmed by WGS; the remaining 5 were 1 mm below the EUCAST DD breakpoint. Only one isolate was detected as BLPACR by CLSI DD. Group III mutations associated with high-level ampicillin resistance were identified in 10/32 isolates., Conclusions: The EUCAST DD susceptibility method is more reliable than either CLSI or BMD for the detection of genotypically defined BLNAR resistance. However, accurate categorization of amoxicillin/clavulanate resistance remains problematic. Continuous and reproducible surveillance of resistance is needed; for this to be possible, robust susceptibility methods are required., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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47. Progress towards a coordinated, national paediatric antimicrobial resistance surveillance programme: Staphylococcus aureus, enterococcal and Gram-negative bacteraemia in Australia.
- Author
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Campbell AJ, Daley DA, Bell JM, Pang S, Coombs GW, Carapetis JR, Bowen AC, and Blyth CC
- Subjects
- Adult, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Australia epidemiology, Child, Drug Resistance, Bacterial, Enterococcus, Humans, Microbial Sensitivity Tests, Prospective Studies, Staphylococcus aureus, Anti-Infective Agents pharmacology, Bacteremia drug therapy, Bacteremia epidemiology
- Abstract
Background: There is increasing knowledge of antimicrobial usage in children yet limited availability of nationally representative paediatric-specific data on antimicrobial resistance., Objectives: Paediatric data from this national surveillance programme are presented to explore differences between childhood and adult bloodstream infections and antimicrobial resistance surveillance., Methods: Using information collected from a prospective coordinated antimicrobial resistance surveillance programme, children ≤18 years and adults >18 years with a positive blood culture for Staphylococcus aureus, Enterococcus spp. or Gram-negative spp. presenting to one of 34 Australian hospitals during 2013-16 were evaluated. Consistent methodologies for key sepsis pathogens were employed and a comparative analysis between children and adults was conducted., Results: There are stark contrasts between children and adults in this national antimicrobial resistance (AMR) data set. Notable differences include lower rates of AMR, different clinical and molecular phenotypes and lower mortality amongst children. The burden of Gram-negative resistance is disproportionately experienced in children, with higher odds of death with an ESBL versus non-ESBL bacteraemia in comparison with adults., Conclusions: These data support that children are not just 'little adults' in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility, clinical phenotype and genetic virulence factors. Antimicrobial surveillance incorporated into routine laboratory practice is vital to inform an array of wider applications including antimicrobial guidelines, stewardship and direction for prioritization of novel antimicrobial development., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
48. Investigation of a Lomentospora prolificans case cluster with whole genome sequencing.
- Author
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Boan P, Pang S, Gardam DJ, Darragh H, Wright M, and Coombs GW
- Abstract
Lomentospora prolificans has caused outbreaks in immunocompromised patients. We performed whole genome sequencing (WGS) on 4 L. prolificans isolates from infections occurring during an 8-month period in the haematology unit at Hospital 1., and 2 isolates from unrelated infections at Hospital 2., showing a high number of mutational differences (>10,000 single nucleotide polymorphisms) between L. prolificans isolates from Hospital 1. Novel typing of isolates by WGS did not demonstrate a single causative strain., Competing Interests: There are none, (© 2020 The Authors.)
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- 2020
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49. A multicentre outbreak of ST45 MRSA containing deletions in the spa gene in New South Wales, Australia.
- Author
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Beukers AG, Newton P, Hudson B, Ross K, Gottlieb T, O'Sullivan M, Daley DA, Pang S, Coombs GW, and van Hal SJ
- Subjects
- Australia epidemiology, Disease Outbreaks, Humans, Microbial Sensitivity Tests, New South Wales epidemiology, Staphylococcus aureus, Bacteremia, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
Background: Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45., Objectives: To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia., Methods: WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed., Results: Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this 'spa-deletion' MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations., Conclusions: This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new 'spa-deletion' MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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- View/download PDF
50. Marked increase in community-associated methicillin-resistant Staphylococcus aureus infections, Western Australia, 2004-2018.
- Author
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Bloomfield LE, Coombs GW, Tempone S, and Armstrong PK
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Toxins genetics, Bacterial Toxins metabolism, Child, Child, Preschool, Community-Acquired Infections epidemiology, Exotoxins genetics, Exotoxins metabolism, Female, Genotype, Humans, Incidence, Infant, Leukocidins genetics, Leukocidins metabolism, Male, Methicillin-Resistant Staphylococcus aureus classification, Middle Aged, Retrospective Studies, Risk Factors, Western Australia epidemiology, Young Adult, Community-Acquired Infections microbiology, Methicillin-Resistant Staphylococcus aureus isolation & purification, Staphylococcal Infections epidemiology, Staphylococcal Infections microbiology
- Abstract
This study presents enhanced surveillance data from 2004 to 2018 for all community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) specimens collected in Western Australia (WA), and describes the changing epidemiology over this period. A total of 57 557 cases were reviewed. Annual incidence rates increased from 86.2 cases per 100 000 population to 245.6 per 100 000 population (IRR = 2.9, CI95 2.7-3.0). The proportion of isolates carrying Panton-Valentine leucocidin (PVL)-associated genes increased from 3.4% to 59.8% (χ2 test for trend 7021.9, P < 0.001). The emergence of PVL-positive, 'Queensland CA-MRSA' (ST93-IV) and 'WA 121' (ST5-IV) accounted for the majority of increases in CA-MRSA across the study period. It is unclear why some clones are more prolific in certain regions. In WA, CA-MRSA rates increase as indices of temperature and humidity increase after controlling for socioeconomic disadvantage. We suggest climatic conditions may contribute to transmission, along with other socio-behavioural factors. A better understanding of the ability for certain clones to form ecological niches and cause outbreaks is required.
- Published
- 2020
- Full Text
- View/download PDF
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