Penicillin-clavulanate susceptibility in clinical methicillin-resistant Staphylococcus aureus bloodstream infection strains from the CAMERA2 trial
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Objectives
Among clinical methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) strains, we sought to determine the prevalence of β-lactam-β-lactamase inhibitor (BLBLI) susceptibility, and its’ association with oxacillin susceptibility, genotypic factors, and patient characteristics.
Methods
Clinical MRSA BSI strains were tested for susceptibility to penicillin-clavulanate by Etest (n=117, 36% of the dataset) and to oxacillin by disk diffusion assay (n=328, 100%). Penicillin-clavulanate susceptibility was defined as MIC≤ 2mg/L and oxacillin disk susceptibility as an inhibition zone >6mm. All strains were whole-genome sequenced, and alleles of mecA annotated. The sensitivity and specificity of the oxacillin disk to predict penicillin-clavulanate ‘susceptibility’ were assessed. Clinical and genomic associations with BLBLI ‘susceptibility’ were assessed by calculating odds-ratios (OR).
Results
We found 73/117 (62%) and 205/328 (62%) strains to be ‘susceptible’ to penicillin-clavulanate and oxacillin disk, respectively. Oxacillin disk susceptibility and penicillin-clavulanate susceptibility were highly correlated (sensitivity 97.3% and specificity 95.5%). We therefore used oxacillin disk susceptibility as a proxy for penicillin-clavulanate susceptibility. Comparative genomics of the mecA gene uncovered 8 alleles. The oxacillin disk ‘susceptible’ phenotype was associated with specific mecA alleles, community-associated MRSA sequence-types (OR 72.8, 95%CI 35.4-162), community acquisition of infection (OR 2.09, 95% CI 1.03-4.27), lower Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.98) and SOFA (sequential organ failure assessment) scores at presentation (OR 0.88, 95% CI 0.79-0.98).
Conclusion
BLBLI ‘susceptibility’ is common among MRSA strains and is strongly associated with the strain genotype. Infections caused by BLBLI ‘susceptible’ strains are associated with specific patients’ characteristics, namely younger age, fewer comorbidities, acquisition in the community and milder presentations.
Summary
In an analysis of the CAMERA2 MRSA strains, β-lactam-β-lactamase inhibitors ‘susceptibility’ was strongly associated with the strain genotype and with specific patients’ characteristics, namely younger age, fewer comorbidities, acquisition in the community and milder presentations.
