An Association Between Bacterial Genotype Combined With a High-Vancomycin Minimum Inhibitory Concentration and Risk of Endocarditis in Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

Miller, Clare E.; Batra, Rahul; Cooper, Ben; Patel, Amita; Klein, John L.; Otter, Jonathan A.; Kypraios, Theodore; French, Gary; Tosas, Olga; Edgeworth, Jonathan D

doi:10.1093/cid/cir858

Cited by 35 publications

(36 citation statements)

References 40 publications

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“…A total of 16 isolates from BSIs were selected from a collection defined in a previous study [2] (Table 1): four CC22 high V-MIC (defined as V-MIC 1.5 mg l À1 ; hereafter 'CC22-high'), four CC30 high V-MIC (hereafter 'CC30-high'), four CC22 low V-MIC (defined as V-MIC 0.38-0.5 mg l À1 ; hereafter 'CC22-low') and four CC30 low V-MIC (hereafter 'CC30-low'); V-MIC was measured by Etest (AB Biodisk). All isolates in the collection had a V-MIC within the susceptible range (<4 mg l À1 ) and there were no hVISA isolates [2].…”

Section: Methodsmentioning

confidence: 99%

“…All isolates in the collection had a V-MIC within the susceptible range (<4 mg l À1 ) and there were no hVISA isolates [2]. S. aureus (Newman) was used as positive control for fibrinogen binding and S. aureus (8325-4) was used as a positive control for fibronectin binding (both kindly supplied by R. Massey, Bath, UK).…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study, we found evidence through analysis of collection of 821 consecutive MRSA BSI isolates that CC22 isolates with an elevated vancomycin (V)-MIC within the susceptible range (1.5-2 mg l À1 ) were strongly associated with endocarditis [2]. This suggests that both lineageassociated characteristics of CC22 and a consequence of reduced vancomycin susceptibility, either bacterial or treatment-related, contribute to the risk of developing endocarditis.…”

Section: Introductionmentioning

confidence: 99%

“…There has been interest in understanding whether strains causing severe infections such as endocarditis have distinct genotypic or phenotypic characteristics [2][3][4][5][6]. Clonal complex (CC) 30 meticillin-resistant S. aureus (MRSA) [3,4] and other MRSA CCs [5] have been associated with endocarditis, whereas other studies have found no association between clones and endocarditis [6].…”

Section: Introductionmentioning

confidence: 99%

“…Vancomycin-intermediate S. aureus (VISA) (4-8 mg l À1 ) and heteroresistant [(h)VISA] isolates have also been associated with endocarditis [1][2][3]7]. VISA and hVISA isolates have multiple phenotypic and metabolic differences compared with susceptible isolates, such as reduced autolysis and gradual thickening of the cell wall, changes in global gene regulators including down-regulation of agr, increased expression of surface adhesins that bind fibrinogen and fibronectin, and attenuated virulence [3,[8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

Marbach

Boakes

Lynham

et al. 2017

Journal of Medical Microbiology

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Purpose. We previously identified an association between CC22 meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection isolates with an elevated vancomycin MIC (V-MIC) in the susceptible range (1.5-2 mg l À1 ) and endocarditis. This study explores whether these isolates have a specific phenotype consistent with the clinical findings.Methodology. CC22 and CC30 MRSA isolates with high (1.5-2 mg l À1 ) and low ( 0.5 mg l À1 ) V-MICs were tested for fibrinogen and fibronectin binding, virulence in a Galleria mellonella caterpillar model, phenol soluble modulin production and accessory gene regulator (agr) expression.Results. CC22 high V-MIC, but not CC30 high V-MIC isolates, showed sustained fibrinogen binding through a stationary growth phase and increased PSM production, specifically PSMa1, compared with respective low V-MIC isolates. Expression was lower in both CC22 and CC30 high V-MIC isolates compared with respective low V-MIC isolates, although there was no associated reduction in virulence in the caterpillar model. Conclusions.The identification of a distinct phenotype for CC22 high V-MIC isolates supports the hypothesis that bacterial factors contribute to the mechanism underlying their association with endocarditis. Further study of these isolates could shed light on the molecular mechanism of endocarditis in humans.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

Marbach

Boakes

Lynham

et al. 2017

Journal of Medical Microbiology

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Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients WithStaphylococcus aureusBloodstream Infections

Kalil

Schooneveld

Fey

et al. 2014

JAMA

163

100

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In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.

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Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study

Juan

Pérez-Montarelo

Viedma

et al. 2017

Eur J Clin Microbiol Infect Dis

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Even with appropriate clinical management, complicated methicillin-susceptible Staphylococcus aureus (MSSA) catheter-related bacteremia (CRB) is frequent. We investigated the influence of molecular characteristics of MSSA strains on the risk of complicated bacteremia (CB) in MSSA-CRB. A multicenter prospective study was conducted in Spain between 2011 and 2014 on MSSA-CRB. Optimized protocol-guided clinical management was required. CB included endocarditis, septic thrombophlebitis, persistent bacteremia and/or end-organ hematogenous spread. Molecular typing, agr functionality and DNA microarray analysis of virulence factors were performed in all MSSA isolates. Out of 83 MSSA-CRB episodes included, 26 (31.3%) developed CB. MSSA isolates belonged to 16 clonal complexes (CCs), with CC30 (32.5%), CC5 (15.7%) and CC45 (13.3) being the most common. Comparison between MSSA isolates in episodes with or without CB revealed no differences regarding agr type and functionality. However, our results showed that CC15 and the presence of genes like cna, chp and cap8 were associated with the development of CB. The multivariate analysis highlighted that the presence of cna (Hazard ratio 2.9; 95% CI 1.14-7.6) was associated with the development of CB. Our results suggest that particular CCs and specific genes may influence the outcome of MSSA-CRB.

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An Association Between Bacterial Genotype Combined With a High-Vancomycin Minimum Inhibitory Concentration and Risk of Endocarditis in Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

Abstract: An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.

Cited by 35 publications

References 40 publications

Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility

Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients WithStaphylococcus aureusBloodstream Infections

Pathogen-related factors affecting outcome of catheter-related bacteremia due to methicillin-susceptible Staphylococcus aureus in a Spanish multicenter study

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