Additional biomarkers and emm types associated with group A streptococcal toxic shock syndrome: a Japanese nationwide observational study

Purpose: The incidence of invasive Group A Streptococcus (iGAS) infection and streptococcal toxic shock syndrome (STSS) is increasing. Early detection and diagnosis of cases that may progress to STSS are currently difficult. In this study, we aimed to identify biomarkers and emm type, one of the virulence factors, associated with STSS development. Methods: In this multicentre observational study including patients with iGAS infection (n = 305), we investigated the relative associations of host factors, clinical manifestations, biomarkers, and emm type with STSS. Results: The overall mortality rate was 15.4%; the fatality rate within 28 days of admission was higher in patients with STSS (67.9%, 38/56) than in those without (3.6%, 9/249). The most predominant type was emm1 (38%), detected in 73.2% of the patients with STSS. Risk factors for STSS identified by multivariable analysis included underlying kidney disease (odds ratio [OR], 10.7; 95% confidence interval [CI], 2.1–54.0, p = 0.004), bacteraemia without primary focus (OR, 3.6; 95% CI 1.2–11.1, p = 0.023), necrotizing fasciitis (OR, 8.7; 95% CI 2.6–29.4, p < 0.001), white blood cell count (WBC) < 4,000/µL (OR, 7.8; 95% CI 2.4–25.6, p = 0.001), serum creatine kinase (CK) ≥ 300 U/L (OR, 7.5; 95% CI 2.8–19.8, p < 0.001), and emm1 (OR, 5.2; 95% CI 2.0–13.4, p = 0.001). Conclusion: WBC < 4,000/µL and CK level ≥ 300 U/L on admission are additional relevant biomarkers for STSS prediction. The most predominant iGAS type, emm1, was significantly associated with STSS.