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Targeting Biofilm Associated Staphylococcus aureus Using Resazurin Based Drug-susceptibility Assay
Published on: May 5, 2016
Vancomycin MICs and risk of complicated bacteremia by glycopeptide-susceptible Staphylococcus aureus
Rocío Falcón1, Eva Mateo1, Rosa Oltra2
1Microbiology Service, Fundación INCLIVA, Hospital Clínico Universitario, Av. Blasco Ibáñez 17, 46010, Valencia, Spain.
Abstract:
Vancomycin (VAN) minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus (S. aureus), as measured by the Etest method, have been associated with poor clinical outcomes of S. aureus bloodstream infections, as has the isolate's genetic background. Here, we assessed the impact of VAN MICs, as determined by a broth microdilution method (BMD) that incorporates incremental VAN concentrations between the conventional log2 dilutions, isolate susceptibility to killing by human phagocytes, acting as a surrogate marker for bacterial cell wall thickness, and S. aureus genetic composition, on the development of complicated S. aureus bacteremia (SAB). We carried out a retrospective, observational single-center cohort study of 148 consecutive patients with SAB caused by methicillin-susceptible (MSSA) isolates (n = 113) or methicillin-resistant (MRSA) isolates (n = 35). S. aureus isolates were genotyped using a commercially available DNA microarray. Overall, VAN MICs of S. aureus isolates taken from complicated and uncomplicated SAB were comparable, irrespective of the testing method (P = 0.19 with BMD, and P = 0.94 with Etest). Likewise, S. aureus isolates in both comparison groups had the same susceptibility to killing by human phagocytes (P = 0.5). Among the genes screened by the S. aureus DNA array, only Sec and Sel were differentially present among S. aureus isolates in both groups (overrepresented in those causing complications) and their presence was associated independently with complicated SAB in multivariate models adjusted for potentially relevant clinical covariates. Separate analysis of MSSA SAB episodes yielded similar results.
Insights
Vancomycin (VAN) MICs and phagocyte susceptibility did not predict complicated Staphylococcus aureus bacteremia (SAB). However, specific bacterial genes (Sec and Sel) were linked to complicated SAB outcomes.
Area of Science:
- Infectious Diseases
- Microbiology
- Genetics
Background:
- Vancomycin (VAN) minimum inhibitory concentrations (MICs) at the upper susceptible range for Staphylococcus aureus (S. aureus) and isolate genetic background have been linked to poor outcomes in S. aureus bloodstream infections (SAB).
- Accurate prediction of complicated SAB requires understanding the interplay between VAN susceptibility, bacterial virulence factors, and host immune response.
Purpose of the Study:
- To assess the impact of VAN MICs (using a refined broth microdilution method), S. aureus susceptibility to phagocyte killing (as a marker for cell wall thickness), and S. aureus genetic composition on the development of complicated SAB.
- To identify specific genetic markers associated with complicated SAB.
Main Methods:
- Retrospective, observational single-center cohort study of 148 patients with SAB (113 methicillin-susceptible S. aureus [MSSA], 35 methicillin-resistant S. aureus [MRSA]).
- S. aureus isolates were genotyped using DNA microarray.
- VAN MICs were determined by broth microdilution (BMD) and Etest; phagocyte killing susceptibility was assessed.
Main Results:
- VAN MICs and phagocyte killing susceptibility were comparable between complicated and uncomplicated SAB isolates, regardless of the testing method (BMD: P=0.19; Etest: P=0.94; phagocytosis: P=0.5).
- The S. aureus DNA array identified Sec and Sel genes as differentially present, being overrepresented in isolates from complicated SAB cases.
- Presence of Sec and Sel genes was independently associated with complicated SAB in multivariate analysis.
Conclusions:
- Neither VAN MICs nor phagocyte killing susceptibility effectively predicted complicated SAB in this cohort.
- The bacterial genes Sec and Sel are potential independent predictors of complicated S. aureus bacteremia.
- Further research into the role of Sec and Sel in S. aureus pathogenesis is warranted.
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