From random care to randomized clinical trials of patients with invasive streptococcal infections—research prioritisation and areas of equipoise

Objectives Life-threatening invasive infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis (SDSE) are unpredictable, frequently fatal, and are increasing in incidence globally. In the absence of evidence from randomized controlled trials (RCTs), clinical management for these conditions varies. Understanding current management approaches and areas of clinical equipoise will inform planning of feasible high-impact RCTs. Methods Two web-based surveys were distributed to Staphylococcus aureus Network Adaptive Platform trial clinicians in April 2024. Survey 1 addressed clinical management practices for S. pyogenes and SDSE bacteraemia, research question (domain) priorities, and areas of clinician equipoise. ‘Domains’ included backbone antibiotics (e.g. penicillin and ceftriaxone), adjunctive antibiotics (e.g. clindamycin and linezolid), and immunomodulation (intravenous immunoglobulin). Survey 2 collected aggregate annual numbers of blood culture isolates (bacteraemia episodes) for selected streptococci and enterococci from 2019 to 2023 inclusive. Results Survey-1 respondents ( n = 65 clinicians from nine countries) ranked S. pyogenes as the highest priority pathogen for inclusion in a future RCT, and ‘adjunctive antibiotics’ as the highest priority domain. However, only 51% ( S. pyogenes ) and 65% (SDSE) of respondents were willing to randomize participants with severe disease to receive ‘no adjunctive antibiotics.’ For nonsevere disease, 89% ( S. pyogenes ) and 85% (SDSE) of clinicians were willing to randomize participants to ‘no adjunctive antibiotics.’ Survey 2 ( n = 17 hospitals from six countries) found the mean number of blood culture isolates/site/year to be 24 for S. pyogenes , and 27 for SDSE (2019–2023). Discussion High-quality evidence is needed to guide treatment of patients with invasive streptococcal diseases. Ongoing clinician engagement will enhance research question prioritisation and feasibility for future trials.