A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing Detectable
            <i>mecA</i>
            by a Commercial PCR Assay Compared to Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates

Jones, D L; Elshaboury, Ramy H.; Munson, Erik; Dilworth, Thomas J

doi:10.1128/aac.01396-17

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…The use of molecular microbial genotypic assays to predict antimicrobial susceptibility in bacteria and guide clinical practice is not new and has been applied in Mycobacterium tuberculosis infections [22], Staphylococcus aureus infections [23], and more recently, Enterobacteriaceae [24]. However, there are very few prospective studies using molecular methods to predict antimicrobial susceptibility along with clinical outcomes and none using these methods in the context of increasingly antimicrobial resistant N. gonorrhoeae.…”

Section: Discussionmentioning

confidence: 99%

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

Klausner

Bristow

Soge

et al. 2020

Clinical Infectious Diseases

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Background Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. Methods Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5–10 days post-treatment. Results Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5–100%). Conclusions Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. Clinical Trials Registration NCT02961751.

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Section: Discussionmentioning

confidence: 99%

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

Klausner

Bristow

Soge

et al. 2020

Clinical Infectious Diseases

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“… S. aureus strains which are phenotypically methicillin susceptible but contain the mecA gene have been reported to have a higher risk of persistent bacteraemia, even when treated with vancomycin [80]. AMR elements have been implicated as virulence determinants in another Gram-positive species; Streptococcus pneumoniae , where a PBP variant associated with penicillin tolerance (though not resistance) was associated with meningitis among isolates found in invasive pneumococcal disease [81].…”

Section: Discussionmentioning

confidence: 99%

“…Analysis of SAB over 21 years in the USA showed that within CC-8, the MRSA lineage USA300 was associated with higher rates of metastatic infection compared to the rest of the spa -t008 complex after adjusting for patient and clinical variables [ 79 ]. S. aureus strains which are phenotypically methicillin susceptible but contain the mecA gene have been reported to have a higher risk of persistent bacteraemia, even when treated with vancomycin [ 80 ]. AMR elements have been implicated as virulence determinants in another Gram-positive species; Streptococcus pneumoniae , where a PBP variant associated with penicillin tolerance (though not resistance) was associated with meningitis among isolates found in invasive pneumococcal disease [ 81 ].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study

et al. 2021

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Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.

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“…73 S. aureus strains which are phenotypically methicillin susceptible but contain the mecA gene have been reported to have a higher risk of persistent bacteraemia, even when treated with vancomycin. 74 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Overall, we found MRSA was more prevalent in bacteraemia than carriage in samples, when sampling the population representatively. In the UK at this time MRSA was almost exclusively healthcare associated.…”

Section: Discussionmentioning

confidence: 75%

“…73 S. aureus strains which are phenotypically methicillin susceptible but contain the mecA gene have been reported to have a higher risk of persistent bacteraemia, even when treated with vancomycin. 74 AMR elements have been implicated as virulence determinants in another Gram positive species; Streptococcus pneumoniae , where a PBP variant associated with penicillin tolerance (though not resistance) was associated with meningitis among isolates found in invasive pneumococcal disease. 75…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the hospital environment: a bacterial genome-wide association study

Young

Charlesworth

Earle

et al. 2021

Preprint

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BackgroundStaphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease.MethodsTo investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage.ResultsAll major global lineages were represented in both bacteraemia and carriage, with no evidence for different attack rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (p=10−8.9-10−9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10−5.3) as well as the presence of SCCmec (HMP=10−4.4).Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (p=10−7.1-10−19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (p=10−7.2).ConclusionsIn an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment.Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and hospital-associated carriage, suggesting that AMR increases the propensity not only to survive in hospital environments, but also to cause invasive disease.

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A Retrospective Analysis of Treatment and Clinical Outcomes among Patients with Methicillin-Susceptible Staphylococcus aureus Bloodstream Isolates Possessing Detectable mecA by a Commercial PCR Assay Compared to Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates

Cited by 7 publications

References 13 publications

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the hospital environment: a bacterial genome-wide association study

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