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High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with
Rocío Falcón1, Alba Martínez2, Eliseo Albert1
1Microbiology Service, Hospital Clínico Universitario de Valencia, Fundación INCLIVA, Valencia, Spain.
Abstract:
Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index <60%) compared with those killed efficiently (killing index >70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes.
Insights
High vancomycin MICs in Staphylococcus aureus (S. aureus) bloodstream infections correlate with thicker bacterial cell walls. This may explain reduced killing by human immune cells, impacting patient outcomes.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Vancomycin minimum inhibitory concentrations (MICs) near the susceptible limit for Staphylococcus aureus (S. aureus) are linked to poor outcomes in bloodstream infections.
- The precise mechanisms underlying this association require further investigation.
Purpose of the Study:
- To test if high vancomycin MICs in S. aureus bacteraemia isolates correlate with increased cell wall thickness.
- To determine if high vancomycin MICs are associated with suboptimal bacterial internalization or lysis by human phagocytes.
Main Methods:
- Evaluated 95 S. aureus isolates for vancomycin MICs using Etest.
- Assessed bacterial killing by human phagocytes via a whole blood assay.
- Investigated bacterial internalization using flow cytometry and cell wall thickness via transmission electron microscopy.
Main Results:
- Isolates with suboptimal phagocyte killing (<60% killing index) exhibited significantly higher vancomycin MICs (P=0.006).
- Bacterial cell wall thickness was significantly greater in isolates with lower killing efficiency (P=0.03).
- Bacterial internalization by neutrophils and monocytes was comparable between groups; no genotypic differences were identified.
Conclusions:
- High vancomycin MICs in S. aureus bacteraemia are associated with increased cell wall thickness.
- Thicker cell walls may contribute to reduced intracellular killing by phagocytes, potentially explaining poorer clinical outcomes.
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