Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting

Harris, Tegan M.; Bowen, Asha C; Holt, Deborah C.; Sarovich, Derek S.; Stevens, Kerrie; Currie, Bart J.; Howden, Benjamin P; Carapetis, Jonathan R.; Giffard, Philip M.; Tong, Steven Y. C.

doi:10.1016/j.cmi.2018.04.020

Cited by 15 publications

(23 citation statements)

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“…To our knowledge, this is the first report of trimethoprim‐resistant ST5‐IV in eastern Australia and the first report of trimethoprim‐resistant ST5‐IV from a dog. Importantly—as has been found in isolates from the Northern Territory—the ST5‐IV isolates in this study lack genes conferring sulphonamide resistance ( sulI , sulII , sulIII ) and remain phenotypically susceptible to trimethoprim sulfamethoxazole (Harris et al, ), an increasingly important first‐line human antimicrobial in the treatment of skin and soft tissue infections in populations in which the incidence of MRSA is high.…”

Section: Discussionsupporting

confidence: 53%

“…The two ST5‐IV isolates also carried the trimethoprim resistance gene dfrG . The SCC mec of the two ST5 isolates had near perfect sequence homology with SCC mec type IV o described by Harris et al () with the same incorporation of trimethoprim‐resistant gene dfrG adjacent to IS431 in the third J region of an SCC mec type IV c backbone (Figure ). Panton–Valentine leukocidin genes lukS‐PV and lukF‐PV were present in all four ST93‐IV isolates and both ST5‐IV isolates.…”

Section: Resultsmentioning

confidence: 53%

“…Alignment of SCCmecIVo from a human clinical methicillin‐resistant Staphylococcus aureus ST5 isolate from Central Australia (top)(Harris et al, ) and a commensal S. aureus ST5 isolate from the anterior nares of a dog from western New South Wales, Australia (bottom), showing near perfect sequence homology. SCCmecIVo is characterized by incorporation of trimethoprim‐resistance gene dfrG in the third J region adjacent to IS431.…”

Section: Resultsmentioning

confidence: 99%

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Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

Gemma

Worthing

Gottlieb

et al. 2019

Zoonoses and Public Health

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Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) is a serious public health concern and in Australia, one that disproportionately affects Aboriginal people. Paralleling MRSA in human medicine, methicillin‐resistant S. pseudintermedius (MRSP) is an increasingly prevalent pathogen in veterinary medicine. We aimed to characterize the carriage of MRSA and MRSP in dogs and cats from predominantly Aboriginal communities in a very remote region of New South Wales (NSW), Australia. Pets (303 dogs and 80 cats) were recruited from six communities in western NSW. Three swabs were collected from each animal (anterior nares, oropharynx and perineum) and from skin lesions or wounds (if present) and cultured on selective media for methicillin‐resistant staphylococci. Human host‐adapted community‐associated MRSA representing four multilocus sequence types (ST1‐IV, ST5‐IV, ST72‐IV, ST93‐IV) were isolated from eight dogs (prevalence 2.6%, 95% confidence interval 1.3%–5.1%). Two ST5‐IV isolates from a single dog were phenotypically trimethoprim‐resistant, harbouring trimethoprim‐resistant gene dfrG within the SCCmec type IVo mobile genetic element. MRSA was not isolated from any cats and MRSP was not isolated from any dogs or cats. This study estimated a high prevalence of human host‐adapted community‐associated MRSA carriage in dogs despite an absence of MRSP. This suggests MRSA carried by dogs in remote NSW originate from human hosts. The cycle of transmission between people, dogs and common environmental sources warrants further investigation. To our knowledge, this is the first report of trimethoprim‐resistant ST5‐IV in eastern Australia and the first report of trimethoprim‐resistant ST5‐IV from a dog.

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Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

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Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

Gemma

Worthing

Gottlieb

et al. 2019

Zoonoses and Public Health

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“…Staphylococcus spp. (MRSA and non-MRSA) are considered susceptible to trimethoprim/sulfamethoxazole; however, several studies, including ours, have reported the isolation of trimethoprim/sulfamethoxazole-resistant MRSA and non-MRSA strains from patients ( Harris et al, 2018 , Sato et al, 2018 , Coombs et al, 2019 , Tissot-Dupont et al, 2019 ). In fact, mutability of the Staphylococcus strains, including MRSA strains is a very perplexing issue.…”

Section: Discussionmentioning

confidence: 79%

The extreme drug resistance (XDR) Staphylococcus aureus strains among patients: A retrospective study

Almanaa

Alyahya

Khaled

et al. 2020

Saudi Journal of Biological Sciences

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The objective of the present work was to observe and profile various antibiotic resistant strains of Staphylococcus aureus and highlight the need for continuous surveillance. Data regarding antibiotic-resistant S. aureus strains isolated and identified at the Medical Microbiology Department, King Khalid Hospital, Riyadh was obtained. Bacterial isolates were collected from several sites of infections in patients and an evaluation of susceptibility were carried out using a fully automated Vitek2 system. Relative frequency (%), odds ratios and Ward's minimum variance were calculated. The results showed that wounds were a source of more than 40% of the S. aureus (MRSA) strains that have ability to resist methicillin, and more than 45% of the methicillin-susceptible S. aureus (non-MRSA) strains. 40% of the isolates were MRSA (N = 251), and all MRSA strains were sensitive to vancomycin, daptomycin, teicoplanin, tigecycline, nitrofurantoin, and itraconazole while all non-MRSA (N = 338) strains were sensitive to vancomycin, cefoxitin, daptomycin, gentamicin, oxacillin, teicoplanin, tigecycline, and mupirocin. Strength of association between antibiotic-resistant S. aureus strains and source of samples (site of infection) was established. The study concluded that S. aureus strains had developed resistance towards 20 (for non-MRSA) and 22 (for MRSA) of the antibiotics tested. All MRSA strains were non-sensitive to amoxicillin/clavulanate, ampicillin cefoxitin, cefazolin, imipenem, oxacillin, and penicillin.

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“…A search for potential markers of resistance to sulfamethoxazole across the genome demonstrated the absence of acquired sulfonamide resistance genes sulI, sulII, and sulIII. No nonsynonymous mutations in the chromosomal dihydropteroate synthase gene folP were observed in a comparison with an SXT-susceptible isolate (SST2096_S1A_SA1) (16). A maximum-parsimony phylogenomic tree was generated from 2,418 biallelic orthologous single nucleotide polymorphisms (SNPs) identified by the alignment of the ST5 isolates to Mu50 (NCBI reference sequence NC_002758.2 [GenBank accession no.…”

Section: Resultsmentioning

confidence: 99%

Clinical and Molecular Epidemiology of an Emerging Panton-Valentine Leukocidin-Positive ST5 Methicillin-Resistant Staphylococcus aureus Clone in Northern Australia

McGuinness

Holt

Harris

et al. 2021

mSphere

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Recently, we identified a Staphylococcus aureus sequence type 5 (ST5) clone in northern Australia with discrepant trimethoprim-sulfamethoxazole (SXT) susceptibility results. We aimed to identify isolates of this clone using Vitek 2 SXT resistance as a proxy and to compare its epidemiology with those of other circulating S. aureus strains. We collated Vitek 2 susceptibility data for S. aureus isolates collected through our laboratory and conducted a prospective, case-control study comparing clinical, microbiological, epidemiological, and genomic data for subsets of isolates reported as SXT resistant (cases) and SXT susceptible (controls) by Vitek 2. While overall SXT resistance rates remained relatively stable from 2011 to 2018 among 27,721 S. aureus isolates, non-multidrug-resistant methicillin-resistant S. aureus (MRSA) strains almost completely replaced multidrug-resistant MRSA strains as the predominant SXT-resistant MRSA phenotype. Demographic and clinical features of 51 case-control pairs were similar, but genotyping revealed stark differences: clonal complex 5 (CC5) MRSA predominated among SXT-resistant cases (34/51 [67%]), while CC93 MRSA predominated among susceptible controls (26/51 [51%]). All CC5 isolates were an ST5 clonal lineage that possessed the trimethoprim resistance gene dfrG within SCCmec IVo; all were SXT susceptible by Etest. The replacement of Vitek 2 reported SXT-resistant multidrug-resistant MRSA by non-multidrug-resistant MRSA appears related to the emergence of an ST5-MRSA-SCCmec IVo clone that is SXT susceptible by Etest and causes clinical disease similar to that caused by ST93-MRSA-SCCmec IVa. Reliance on Vitek 2 SXT reporting may lead to unnecessary restriction of effective oral treatment options for S. aureus infections. Whether the presence of dfrG within SCCmec IVo provides a selective advantage at the population level is currently unclear. IMPORTANCE Staphylococcus aureus is an important human pathogen that causes a wide range of clinical infections. In the past 2 decades, an epidemic of community-associated skin and soft tissue infections has been driven by S. aureus strains with specific virulence factors and resistance to beta-lactam antibiotics. Recently, an S. aureus strain with discrepant antimicrobial susceptibility testing results has emerged in northern Australia. This ST5-MRSA-SCCmec IVo clone is reported as resistant to trimethoprim-sulfamethoxazole by Vitek 2 but susceptible by phenotypic methods. ST5-MRSA-SCCmec IVo is now the second most common community-associated MRSA clone in parts of Australia and causes a spectrum of clinical disease similar to that caused by the virulent ST93-MRSA lineage. Whole-genome sequence analysis demonstrates that ST5-MRSA-SCCmecIVo is causing a clonal outbreak across a large geographical region. Although phenotypic testing suggests in vitro susceptibility to trimethoprim-sulfamethoxazole, it is unclear at this stage whether the presence of dfrG within SCCmec IVo provides a selective advantage at the population level.

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Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting

Cited by 15 publications

References 4 publications

Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

The extreme drug resistance (XDR) Staphylococcus aureus strains among patients: A retrospective study

Clinical and Molecular Epidemiology of an Emerging Panton-Valentine Leukocidin-Positive ST5 Methicillin-Resistant Staphylococcus aureus Clone in Northern Australia

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