Penicillin-clavulanate susceptibility in clinical methicillin-resistant Staphylococcus aureus bloodstream infection strains from the CAMERA2 trial
- 1The Peter Doherty Institution at the University of Melbourne
Abstract
ObjectivesAmong clinical methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) strains, we sought to determine the prevalence of {beta}-lactam-{beta}-lactamase inhibitor (BLBLI) susceptibility, and its association with oxacillin susceptibility, genotypic factors, and patient characteristics.
MethodsClinical 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).
ResultsWe 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).
ConclusionBLBLI 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.
SummaryIn an analysis of the CAMERA2 MRSA strains, {beta}-lactam-{beta}-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.
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BibTeX
@misc{petersiel2026penicillinclavulanate,
title = {{Penicillin-clavulanate susceptibility in clinical methicillin-resistant Staphylococcus aureus bloodstream infection strains from the CAMERA2 trial}},
author = {N. Petersiel and M. Duarte-Aguilera and D. Daniel and A. S. Hayes and J. S. Davis and B. P. Howden and S. G. Giulieri and S. Tong and The Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Study Group},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.26363520},
url = {https://www.medrxiv.org/content/10.64898/2026.09.20.26363520v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Penicillin-clavulanate susceptibility in clinical methicillin-resistant Staphylococcus aureus bloodstream infection strains from the CAMERA2 trial
AU - N. Petersiel
AU - M. Duarte-Aguilera
AU - D. Daniel
AU - A. S. Hayes
AU - J. S. Davis
AU - B. P. Howden
AU - S. G. Giulieri
AU - S. Tong
AU - The Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Study Group
PY - 2026
DA - 2026/09/20
PB - medRxiv
DO - 10.64898/2026.09.20.26363520
UR - https://www.medrxiv.org/content/10.64898/2026.09.20.26363520v1
AB - ObjectivesAmong clinical methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) strains, we sought to determine the prevalence of {beta}-lactam-{beta}-lactamase inhibitor (BLBLI) susceptibility, and its association with oxacillin susceptibility, genotypic factors, and patient characteristics. MethodsClinical 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). ResultsWe 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). ConclusionBLBLI 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. SummaryIn an analysis of the CAMERA2 MRSA strains, {beta}-lactam-{beta}-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.
ER -