226 results on '"Coombs GW"'
Search Results
2. 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, Mowlaboccus, S, 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 bac
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- 2022
3. Prevalence of MRSA strains among Staphylococcus aureus isolated from outpatients, 2006. Report from the Australian Group for Antimicrobial Resistance
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Australian Group for Antimicrobial Resistance, Coombs, GW, Bell, JM, Pearson, JC, Collignon, PJ, Nimmo, GR, McLaws, ML, and Christiansen, KJ
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- 2009
4. 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
5. Complete Genome Sequence of Community-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 1, SCCmec IV[2B], Isolated in the 1990s from Northern Western Australia
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Gill, SR, Karakatsanis, NM, Mowlaboccus, S, Colombi, E, Pearson, JC, Ramsay, JP, Coombs, GW, Gill, SR, Karakatsanis, NM, Mowlaboccus, S, Colombi, E, Pearson, JC, Ramsay, JP, and Coombs, GW
- Abstract
Sequence type 1 (ST1) methicillin-resistant Staphylococcus aureus (MRSA) SCCmec 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
6. Complete Genome Sequences of Three of the Earliest Community-Associated Methicillin-Resistant Staphylococcus aureus Strains Isolated in Remote Western Australia
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Gill, SR, Karakatsanis, NM, Colombi, E, Mowlaboccus, S, Pearson, JC, Coombs, GW, Ramsay, JP, Gill, SR, 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
7. Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent
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Planet, PJ, Torres, VJ, Steinig, EJ, Duchene, S, Robinson, DA, Monecke, S, Yokoyama, M, Laabei, M, Slickers, P, Andersson, P, Williamson, D, Kearns, A, Goering, RV, Dickson, E, Ehricht, R, Ip, M, O'Sullivan, MVN, Coombs, GW, Petersen, A, Brennan, G, Shore, AC, Coleman, DC, Pantosti, A, de Lencastre, H, Westh, H, Kobayashi, N, Heffernan, H, Strommenger, B, Layer, F, Weber, S, Aamot, HV, Skakni, L, Peacock, SJ, Sarovich, D, Harris, S, Parkhill, J, Massey, RC, Holden, MTG, Bentley, SD, Tong, SYC, Planet, PJ, Torres, VJ, Steinig, EJ, Duchene, S, Robinson, DA, Monecke, S, Yokoyama, M, Laabei, M, Slickers, P, Andersson, P, Williamson, D, Kearns, A, Goering, RV, Dickson, E, Ehricht, R, Ip, M, O'Sullivan, MVN, Coombs, GW, Petersen, A, Brennan, G, Shore, AC, Coleman, DC, Pantosti, A, de Lencastre, H, Westh, H, Kobayashi, N, Heffernan, H, Strommenger, B, Layer, F, Weber, S, Aamot, HV, Skakni, L, Peacock, SJ, Sarovich, D, Harris, S, Parkhill, J, Massey, RC, Holden, MTG, Bentley, SD, and Tong, SYC
- Abstract
The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated
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- 2019
8. Clonal diversity and geographic distribution of methicillin-resistant Staphylococcus pseudintermedius from Australian animals: Discovery of novel sequence types
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Worthing, KA, Abraham, S, Coombs, GW, Pang, S, Saputra, S, Jordan, D, Trott, DJ, Norris, JM, Worthing, KA, Abraham, S, Coombs, GW, Pang, S, Saputra, S, Jordan, D, Trott, DJ, and Norris, JM
- Abstract
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an increasingly prevalent pathogen in veterinary medicine. This study examined the molecular epidemiology of clinical MRSP isolated from Australian animals. Clinical staphylococci submitted to all Australian veterinary diagnostic laboratories were collected during 2013 and identified using traditional phenotypic tests and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Phenotypic antimicrobial resistance was determined using broth microdilution and disk diffusion. MRSP isolates were characterized by whole genome sequencing which included identification of the mecA gene. Phylogenetic relationships were inferred by comparison of single nucleotide polymorphisms. Of the 669 S. pseudintermedius isolates collected from dogs, cats and cattle, 77 (11.5%) were MRSP. Nineteen multilocus sequence types (STs) were identified, with most isolates belonging to one of five STs (ST71, ST497, ST316, ST496 and ST45). Phylogenetic analysis revealed that Australian ST71 appears closely related to ST71 from overseas. ST497 and ST496 represented novel sequence types, not previously reported outside Australia. Most other STs were novel and only distantly related to each other. Geographical clustering of STs was observed. All isolates belonging to the five main STs were multi- to extensively- drug resistant while isolates from singleton STs generally had lower levels of antimicrobial resistance. The frequency of ciprofloxacin, trimethoprim-sulfamethoxazole, gentamicin, chloramphenicol and tetracycline resistance varied significantly between STs (p<0.01). Australian MRSP isolates are phylogenetically diverse, with a mix of previously unreported and well known international MRSP clones that demonstrate geographic clustering and exhibit both multidrug-resistant and extensively drug-resistant phenotypes.
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- 2018
9. Vancomycin-resistant Enterococcus faecium sequence type 796-rapid international dissemination of a new epidemic clone
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Mahony, AA, Buultjens, AH, Ballard, SA, Grabsch, EA, Xie, S, Seemann, T, Stuart, RL, Kotsanas, D, Cheng, A, Heffernan, H, Roberts, SA, Coombs, GW, Bak, N, Ferguson, JK, Carter, GC, Howden, BP, Stinear, TP, Johnson, PDR, Mahony, AA, Buultjens, AH, Ballard, SA, Grabsch, EA, Xie, S, Seemann, T, Stuart, RL, Kotsanas, D, Cheng, A, Heffernan, H, Roberts, SA, Coombs, GW, Bak, N, Ferguson, JK, Carter, GC, Howden, BP, Stinear, TP, and Johnson, PDR
- Abstract
BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. METHODS: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. RESULTS: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. CONCLUSIONS: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.
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- 2018
10. Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia
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van Hal, SJ, Steinig, EJ, Andersson, P, Holden, MTG, Harris, SR, Nimmo, GR, Williamson, DA, Heffernan, H, Ritchie, SR, Kearns, AM, Ellington, MJ, Dickson, E, De Lencastre, H, Coombs, GW, Bentley, SD, Parkhill, J, Holt, DC, Giffard, PM, Tong, SYC, van Hal, SJ, Steinig, EJ, Andersson, P, Holden, MTG, Harris, SR, Nimmo, GR, Williamson, DA, Heffernan, H, Ritchie, SR, Kearns, AM, Ellington, MJ, Dickson, E, De Lencastre, H, Coombs, GW, Bentley, SD, Parkhill, J, Holt, DC, Giffard, PM, and Tong, SYC
- Abstract
Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens.
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- 2018
11. Clonal expansion of new penicillin-resistant clade of serogroup W, clonal complex 11 Neisseria meningitidis, Western Australia
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Mowlaboccus, S, Jolley, KA, Bray, JE, Pang, S, Thin Lee, Y, Bew, JD, Speers, DJ, Keil, AD, Coombs, GW, and Kahler, CM
- Abstract
In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.
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- 2017
12. Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium
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Buultjens, AH, Lam, MMC, Ballard, S, Monk, IR, Mahony, AA, Grabsch, EA, Grayson, ML, Pang, S, Coombs, GW, Robinson, JO, Seemann, T, Johnson, PDR, Howden, BP, Stinear, TP, Buultjens, AH, Lam, MMC, Ballard, S, Monk, IR, Mahony, AA, Grabsch, EA, Grayson, ML, Pang, S, Coombs, GW, Robinson, JO, Seemann, T, Johnson, PDR, Howden, BP, and Stinear, TP
- Abstract
From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments.
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- 2017
13. Genomic insights into the emergence and spread of international clones of healthcare-, community- and livestock-associated meticillin- resistant Staphylococcus aureus: Blurring of the traditional definitions
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Lindsay, J, Bal, AM, Coombs, GW, Holden, MTG, Nimmo, GR, Tattevin, P, and Skov, RL
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biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses - Abstract
The evolution of meticillin-resistant Staphylococcus aureus (MRSA) from meticillin-susceptible S. aureus has been a result of the accumulation of genetic elements under selection pressure from antibiotics. The traditional classification of MRSA into healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) is no longer relevant as there is significant overlap of identical clones between these groups, with an increasing recognition of human infection caused by livestock-associated MRSA (LA-MRSA). Genomic studies have enabled us to model the epidemiology of MRSA along these lines. In this review, we discuss the clinical relevance of genomic studies, particularly whole-genome sequencing, in the investigation of outbreaks. We also discuss the blurring of each of the three epidemiological groups (HA-MRSA, CA-MRSA and LA-MRSA), demonstrating the limited relevance of this classification.
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- 2016
14. Isolation of mecC MRSA in Australia
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Worthing, KA, Coombs, GW, Pang, S, Abraham, S, Saputra, S, Trott, DJ, Jordan, D, Wong, HS, Abraham, RJ, Norris, JM, Worthing, KA, Coombs, GW, Pang, S, Abraham, S, Saputra, S, Trott, DJ, Jordan, D, Wong, HS, Abraham, RJ, and Norris, JM
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- 2016
15. A Prescription for Resistance: Management of Staphylococcal Skin Abscesses by General Practitioners in Australia
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Parrott, C, Wood, G, Bogatyreva, E, Coombs, GW, Johnson, PDR, Bennett, CM, Parrott, C, Wood, G, Bogatyreva, E, Coombs, GW, Johnson, PDR, and Bennett, CM
- Abstract
OBJECTIVES: We investigated the management of staphylococcal abscesses (boils) by general practitioners (GPs) in the context of rising antibiotic resistance in community strains of Staphylococcus aureus. DESIGN, SETTING, PARTICIPANTS: We analyzed patient-reported management of 66 cases of uncomplicated skin abscesses from the frequency matched methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) Community-Onset Staphylococcus aureus Household Cohort (COSAHC) study (Melbourne, Australia, 2008-2012). Susceptibilities in all cases were known: 50/66 abscesses were caused by MRSA. In order to investigate GP-reported management of staphylococcal abscesses, we surveyed a random subset of GPs, from the COSAHC study (41), and of GPs (39) who used the same community-based pathology service (December 2011-May 2012). MAIN OUTCOME MEASURES: Patient outcomes, antibiotics prescribed, antibiotic resistance profiles of infecting strains, rates of incision and drainage (I&D), and attitudes to ordering microbiological cultures. RESULTS: MRSA was three times more likely to be cultured from an abscess than MSSA. Patient-reported management revealed 100% were prescribed antibiotics and only 60.6% had I&D. Of those 85% who remembered their prescription(s), 81% of MRSA cases and 23% of MSSA cases initially received inactive antibiotics. Repeat GP visits where antibiotics were changed occurred in 45 MRSA and 7 MSSA cases, although at least 33% of subsequent prescriptions were inactive for the MRSA infections. Patients treated with I&D and antibiotics did no better than those treated with only I&D, regardless of the antibiotic activity. In the GP surveys, 89% reported I&D, with or without antibiotics, to be their preferred management. Only 29.9% of GPs would routinely swab abscesses. CONCLUSION: The recommended management of uncomplicated Staphylococcus abscesses is I&D without antibiotics to reduce exposure to unnecessary antibiotics. In our study, I&D was perfo
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- 2016
16. First report of a mecA-positive multidrug-resistant Staphylococcus pseudintermedius isolated from a dog in New Zealand
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Bell, AG, primary, Coombs, GW, additional, Cater, B, additional, and Douglass, C, additional
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- 2016
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17. Convergent Adaptation in the Dominant Global Hospital Clone ST239 of Methicillin-Resistant Staphylococcus aureus
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Gilligan, P, Fowler, V, Baines, SL, Holt, KE, Schultz, MB, Seemann, T, Howden, BO, Jensen, SO, van Hal, SJ, Coombs, GW, Firth, N, Powell, DR, Stinear, TP, Howden, BP, Gilligan, P, Fowler, V, Baines, SL, Holt, KE, Schultz, MB, Seemann, T, Howden, BO, Jensen, SO, van Hal, SJ, Coombs, GW, Firth, N, Powell, DR, Stinear, TP, and Howden, BP
- Abstract
UNLABELLED: Infections caused by highly successful clones of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, including walKR, that significantly associate with and may explain these key phenotypes. The phenotypic convergence of two independently evolving ST239 clades highlights the very strong selective pressures acting on HA-MRSA, showing that hospital environments have favored the accumulation of mutations in essential MRSA genes that increase resistance to antimicrobials, attenuate virulence, and promote persistence in the health care environment. Combinations of comparative genomics and careful phenotypic measurements of longitudinal collections of clinical isolates are giving us the knowledge to intelligently address the impact of current and future antibiotic usage policies and practices on hospital pathogens globally. IMPORTANCE: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for innumerable drug-re
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- 2015
18. Australian Enterococcal Sepsis Outcome Programme, 2011
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Coombs,GW, Pearson,JC, Le,T, Daly,DA, Robinson,JO, Gottlieb,T, Howden,BP, Johnson,PD, Bennett,CM, Stinear,TP, Turnidge,JD, Coombs,GW, Pearson,JC, Le,T, Daly,DA, Robinson,JO, Gottlieb,T, Howden,BP, Johnson,PD, Bennett,CM, Stinear,TP, and Turnidge,JD
- Abstract
From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ≤ 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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- 2014
19. Molecular epidemiology of enterococcal bacteremia in Australia
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Coombs, GW, Pearson, JC, Dale, DA, Le, T, Robinson, OJ, Gottlieb, T, Howden, BP, Johnson, PD, Bennett, CM, Stinear, TP, Turnidge, JD, Coombs, GW, Pearson, JC, Dale, DA, Le, T, Robinson, OJ, Gottlieb, T, Howden, BP, Johnson, PD, Bennett, CM, Stinear, TP, and Turnidge, JD
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- 2014
20. Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in New Zealand: Rapid Emergence of Sequence Type 5 (ST5)-SCCmec-IV as the Dominant Community-Associated MRSA Clone
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de Lencastre, H, Williamson, DA, Roberts, SA, Ritchie, SR, Coombs, GW, Fraser, JD, Heffernan, H, de Lencastre, H, Williamson, DA, Roberts, SA, Ritchie, SR, Coombs, GW, Fraser, JD, and Heffernan, H
- Abstract
The predominant community-associated MRSA strains vary between geographic settings, with ST8-IV USA300 being the commonest clone in North America, and the ST30-IV Southwest Pacific clone established as the dominant clone in New Zealand for the past two decades. Moreover, distinct epidemiological risk factors have been described for colonisation and/or infection with CA-MRSA strains, although these associations have not previously been characterized in New Zealand. Based on data from the annual New Zealand MRSA survey, we sought to describe the clinical and molecular epidemiology of MRSA in New Zealand. All non-duplicate clinical MRSA isolates from New Zealand diagnostic laboratories collected as part of the annual MRSA survey were included. Demographic data was collected for all patients, including age, gender, ethnicity, social deprivation index and hospitalization history. MRSA was isolated from clinical specimens from 3,323 patients during the 2005 to 2011 annual surveys. There were marked ethnic differences, with MRSA isolation rates significantly higher in Māori and Pacific Peoples. Over the study period, there was a significant increase in CA-MRSA, and a previously unidentified PVL-negative ST5-IV spa t002 clone replaced the PVL-positive ST30-IV Southwest Pacific clone as the dominant CA-MRSA clone. Of particular concern was the finding of several successful and virulent MRSA clones from other geographic settings, including ST93-IV (Queensland CA-MRSA), ST8-IV (USA300) and ST772-V (Bengal Bay MRSA). Ongoing molecular surveillance is essential to prevent these MRSA strains becoming endemic in the New Zealand healthcare setting.
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- 2013
21. Genomic Insights to Control the Emergence of Vancomycin-Resistant Enterococci
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Parkhill, J, Howden, BP, Holt, KE, Lam, MMC, Seemann, T, Ballard, S, Coombs, GW, Tong, SYC, Grayson, ML, Johnson, PDR, Stinear, TP, Parkhill, J, Howden, BP, Holt, KE, Lam, MMC, Seemann, T, Ballard, S, Coombs, GW, Tong, SYC, Grayson, ML, Johnson, PDR, and Stinear, TP
- Abstract
UNLABELLED: Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm. IMPORTANCE: Enterococcus faecium is an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in ho
- Published
- 2013
22. Genetic diversity among community methicillin-resistant Staphylococcus aureus strains causing outpatient infections in Australia
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Coombs, GW, Nimmo, GR, Bell, JM, Huygens, F, O'Brien, FG, Malkowski, MJ, Pearson, JC, Stephens, AJ, Giffard, Philip Morrison, Australian Group for Antimicrobial Resistance, Coombs, GW, Nimmo, GR, Bell, JM, Huygens, F, O'Brien, FG, Malkowski, MJ, Pearson, JC, Stephens, AJ, Giffard, Philip Morrison, and Australian Group for Antimicrobial Resistance
- Abstract
Increasing reports of the appearance of novel nonmultiresistant methicillin-resistant Staphylococcus aureus MRSA (MRSA) strains in the community and of the spread of hospital MRSA strains into the community are cause for public health concern. We conducted two national surveys of unique isolates of S. aureus from clinical specimens collected from nonhospitalized patients commencing in 2000 and 2002, respectively. A total of 11.7% of 2,498 isolates from 2000 and 15.4% of 2,486 isolates from 2002 were MRSA. Approximately 54% of the MRSA isolates were nonmultiresistant (resistant to less than three of nine antibiotics) in both surveys. The majority of multiresistant MRSA isolates in both surveys belonged to two strains (strains AUS-2 and AUS-3), as determined by pulsed-field gel electrophoresis (PFGE) and resistogram typing. The 3 AUS-2 isolates and 10 of the 11 AUS-3 isolates selected for multilocus sequence typing (MLST) and staphylococcal chromosomal cassette mec (SCCmec) analysis were ST239-MRSA-III (where ST is the sequence type) and thus belonged to the same clone as the eastern Australian MRSA strain of the 1980s, which spread internationally. Four predominant clones of novel nonmultiresistant MRSA were identified by PFGE, MLST, and SCCmec analysis: ST22-MRSA-IV (strain EMRSA-15), ST1-MRSA-IV (strain WA-1), ST30-MRSA-IV (strain SWP), and ST93-MRSA-IV (strain Queensland). The last three clones are associated with community acquisition. A total of 14 STs were identified in the surveys, including six unique clones of novel nonmultiresistant MRSA, namely, STs 73, 93, 129, 75, and 80slv and a new ST. SCCmec types IV and V were present in diverse genetic backgrounds. These findings provide support for the acquisition of SCCmec by multiple lineages of S. aureus. They also confirm that both hospital and community strains of MRSA are now common in nonhospitalized patients throughout Australia.
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- 2004
23. 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
- Abstract
(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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24. 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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25. 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
- Abstract
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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26. 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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27. 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
- Abstract
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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28. 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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29. 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
- Abstract
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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30. 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
- Subjects
- 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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31. 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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32. 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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33. 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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34. 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
- Subjects
- Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Drug Resistance, Bacterial
- Abstract
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.)
- Published
- 2023
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35. 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
- Subjects
- 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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36. 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
- Subjects
- 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)
- Published
- 2023
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37. Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2022.
- Author
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Coombs GW, Daley DA, Shoby P, and Mowlaboccus S
- Subjects
- 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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38. 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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39. Reversible vancomycin susceptibility within emerging ST1421 Enterococcus faecium strains is associated with rearranged vanA-gene clusters and increased vanA plasmid copy number.
- Author
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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
- Subjects
- 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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40. 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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41. 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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42. 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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43. 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
- Subjects
- 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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44. 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.)
- Published
- 2022
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45. 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
- Subjects
- Humans, Escherichia coli genetics, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Fosfomycin pharmacology, Escherichia coli Infections drug therapy
- Published
- 2022
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46. 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
- Subjects
- 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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47. Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Surveillance Outcome Program (AESOP).
- Author
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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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48. Molecular Epidemiology of Penicillin-Susceptible Staphylococcus aureus Bacteremia in Australia and Reliability of Diagnostic Phenotypic Susceptibility Methods to Detect Penicillin Susceptibility.
- Author
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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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49. 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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50. 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.)
- Published
- 2022
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