Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Junk or adjunct? The place of protein synthesis inhibitors for treatment of severe invasive Streptococcus pyogenes infections in a time of rising clindamycin resistance (#109)

Louise Kelly 1 2 , Hannah Frost 1 , Kristy Azzopardi 1 , Danika L Hill 3 , Tony M Korman 4 5 , Katherine Bond 6 7 8 , Mark R Davies 7 , Ouli Xie 4 8 , Andrew C Steer 1 9 10 , Joshua Osowicki 1 9 10
  1. Tropical Diseases Research Group, Murdoch Children's Research Institute , Melbourne, VIC, Australia
  2. Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Dublin, Ireland
  3. Department of Immunology, School of Translational Medicine, Monash University, Melbourne, VIC, Australia
  4. Monash Infectious Diseases, Monash Health, Melbourne, VIC, Australia
  5. Monash University, Melbourne, VIC, Australia
  6. Department of Microbiology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  7. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  8. Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  9. Department of Infectious Diseases, The Royal Children's Hospital Melbourne, Melbourne, VIC, Australia
  10. Department of Paediatrics, University of Melbourne , Melbourne, VIC, Australia

Background

Widespread use of clindamycin as an adjunctive antitoxin therapy for patients with severe invasive Streptococcus pyogenes infections is based on limited data from in vitro and observational clinical studies. However, at least 25% of invasive isolates are now clindamycin resistant in several countries. Linezolid has emerged as a potential alternative protein synthesis inhibitor, with reduced toxicity compared to clindamycin and rare resistance.

 

Aim

Using a well-matched panel of clindamycin susceptible and resistant invasive clinical S. pyogenes strains, we will compare the effects of clindamycin, linezolid, and penicillin in time-kill assays and laboratory models of toxic shock syndrome.

 

Methods

A panel of 5 isolates from M1 and M12 lineages has been established, well-matched by whole genome sequencing besides genes for constitutive or inducible clindamycin resistance (all linezolid susceptible). Time-kill assays will be completed in minimal and enriched media, across a range of clindamycin, linezolid, and penicillin concentrations up to 4x the MIC. Supernatants will be collected at serial timepoints for toxin measurement (including superantigens) and for stimulation of a whole blood toxic shock model with cytokine and flow cytometry readouts. Significant differences between clindamycin and linezolid will be tested in an HLA-humanised murine toxic shock syndrome model. 

 

Conclusion

Alongside efforts towards prospective clinical trials of interventions for life-threatening toxin-mediated Gram-positive infections, it is time to revisit and update the laboratory evidence for adjunctive antitoxin antibiotics. Here, we will present new data for clindamycin and linezolid, helping clinicians caring for these sickest of patients in an era of increasing clindamycin resistance.