Original Research
Sunday, October 13, 2024
12:45 PM–02:15 PM
Abstract
Introduction:
Penicillin resistance mediated by ß-lactamase (blaZ) among methicillin-susceptible Staphylococcus aureus (MSSA) has been ubiquitous for decades. However, recent reports indicate that penicillin-susceptible S. aureus (PSSA) is increasing, coinciding with a time period of the clinical introduction of daptomycin. Daptomycin exposure increases ß-lactam susceptibility, but it is unknown whether emergence of PSSA is an epiphenomenon or directly related to daptomycin use.
Research Question or Hypothesis:
This study evaluated PSSA over time and tested the hypothesis that daptomycin exposure increases penicillin-susceptibility.
Study Design:
MSSA bloodstream isolates were collected over a 13-year period and evaluated for PSSA using phenotypic and genotypic testing. blaZ positive MSSA were exposed to daptomycin via serial daily passage and assessed for PSSA.
Methods:
Penicillin-susceptibility among MSSA bloodstream isolates (2009-2022) were determined by automated testing (MicroScan) and broth microdilution assays. Inducible penicillin-resistance was further tested using the “beach-cliff” disk diffusion phenotype. The presence of blaZ was confirmed by PCR. To evaluate the relationship between PSSA and daptomycin, the MSSA strain TX0117 (blaZ+) was passaged in daptomycin in vitro using daily serial passages and evaluated PSSA.
Results:
Among 1187 MSSA isolates, PSSA consistently increased from 23.7% to 44.3% over the study period. Only 3.2% of the 435 PSSA displayed inducible penicillin resistance, and 71.4% (10 of 14) of these contained blaZ. In daptomycin passage with TX0117 (blaZ+), daptomycin MIC increased 16-fold (0.25 to 4 µg/mL), while the penicillin MIC reduced 32-fold (64 to 2 µg/mL).
Conclusion:
This study observed a steady increase in PSSA among MSSA bloodstream isolates. Inducible penicillin-resistance was rare. Daptomycin exposure appears to directly contribute to PSSA in vitro. Future studies are ongoing to identify whether increasing PSSA in clinical S. aureus bloodstream isolates correlates with daptomycin exposure and clinical use in patients, and whether these changes in susceptibility have implications on bacterial virulence properties.
Presenting Author
Sarah Aragon B.S.University of Wisconsin Madison
Authors
Sue McCrone B.S.
University of Wisconsin-Madison
Warren Rose PharmD
University of Wisconsin-Madison
George Sakoulas MD
University of California- San Diego
Cecilia Volk BA
University of Wisconsin-Madison