Genotypic and phenotypic relationships among methicillin-resistant Staphylococcus aureus from three multicentre bacteraemia studies

Abstract

BackgroundAt a time when the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) was changing, we sought to characterize several genotypic markers and glycopeptide susceptibility features of clinical isolates from patients with bacteraemia.MethodsOne hundred and sixty-eight MRSA bloodstream isolates obtained from three multicentre clinical trials were microbiologically and genotypically characterized.ResultsAll isolates were susceptible to vancomycin (MIC ≤ 2 mg/L); 38% belonged to accessory gene regulator (agr) group I, 52% belonged to group II and 10% belonged to group III. Typing of the staphylococcal cassette chromosome mec (SCCmec) showed that 67% were type II and 33% were type IV. The agr group II polymorphism was associated with SCCmec II (P < 0.001). Fifty-three percent of SCCmec II and 27% of SCCmec IV isolates had vancomycin MICs ≥1 mg/L (P = 0.001). One hundred percent of agr II strains were predicted to be members of clonal complex 5. SCCmec II was the genetic marker most predictive of vancomycin MICs of ≥1 mg/L. SCCmec IV isolates were more likely to have vancomycin MICs ≤0.5 mg/L.ConclusionsGiven that SCCmec IV is a marker for a community-based organism for which less prior vancomycin exposure is predicted, we conclude that prior antibiotic exposure in agr group II organisms may account for their increased vancomycin MICs.

Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates

“…We confirmed previous findings that agr type II and agr dysfunction were associated with elevated vancomycin MIC and reduced vancomycin susceptibility (10,13,27), and these have also been linked to poor outcomes (12). However, the association between elevated vancomycin MIC and mortality may not necessarily be explained by agr dysfunction alone, as these isolates have been shown to be less virulent in an invertebrate model (30).…”

“…For example, MRSA strains with staphylococcal cassette chromosome mec element (SCCmec) types II/III typically have higher vancomycin MICs than strains with SCCmec types IV/V (9). agr type II has been associated with reduced vancomycin susceptibility (10), even in MSSA (11), and agr dysfunction has been associated with mortality (12) and other suboptimal outcomes (13). Specific genotypes have also been associated with elevated vancomycin MIC, such as non-CC22/30 clones in a study of MRSA bacteremia (14), or infection syndromes that have increased mortality, such as endocarditis or other invasive disease (14)(15)(16).…”

Predictors of Relapse of Methicillin-Resistant Staphylococcus aureus Bacteremia after Treatment with Vancomycin

“…The majority of recurrent episodes of MRSA bacteremia after vancomycin treatment in our institution were due to relapse (91.7%), as described by other investigations (4, (20). Indeed, SCCmec II was associated with elevated vancomycin MICs in this investigation.…”

Relationship of agr Expression and Function with Virulence and Vancomycin Treatment Outcomes in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

“…It is the most prevalent cause of endovascular infections, including catheter sepsis and infective endocarditis (IE) (8,46), and the second most common cause of bacteremia (8,16). The increase in infections due to methicillin-resistant S. aureus (MRSA), the high rates of vancomycin clinical treatment failures, and the growing problems of linezolid and daptomycin resistance have all further complicated the management of patients with MRSA infections and have led to high health care costs (2,9,15,30). In addition, MRSA bacteremia and IE are associated with high rates of morbidity and mortality (15 to 40%), even with seemingly appropriate antimicrobial therapy (9,20).…”