Severe invasive Streptococcus pyogenes infections: A 15-year observational study with molecular characterization of isolates among intensive care adults

Abstract

Background: Improving outcomes among patients with invasive group A Streptococcus pyogenes (iGAS) infections is an unmet clinical need. The main objective of this study was to analyze epidemiological and outcome differences in adults admitted to the intensive care unit (ICU) with iGAS infection over a 15-year period and to evaluate the impact of M1uk isolates and clindamycin optimization on patient outcomes.

Methods: This was a single-center observational study conducted at the ICU of Donostia University Hospital, located in Donostia, Spain. The recruitment of all consecutive adult patients admitted to the ICU by iGAS was carried out from January 2010 to May 2024 and divided into three periods: pre-pandemic (January 2010-2019), pandemic (2020-2021), and post-pandemic (May 2022-2024). The main outcome variables were ICU length of stay, hospital length of stay, and ICU mortality. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software (version 25; SPSS Inc., Chicago, IL, USA). A significance level of P <0.05 was considered for all analyses.

Results: Sixty-eight adults were enrolled, with a crude mortality in pre- and post-pandemic periods being 25.5% and 10.0% (P=0.200), respectively. Twenty (29.4%) were respiratory and 29 (41.2%) were soft tissue infections. The incidence had valleys (<1/100,000) in 2020 and 2021 and peaks (>4/100,000 inhabitants) in 2014, 2019, and 2023. Pre-pandemic patients were significantly younger (median: 58.0 vs. 67.5 years, P <0.050), had lower Charlson scores (median: 0 vs. 2, P=0.009), and required more renal replacement therapy (48.9% vs. 15.0%, P=0.013). Emm1 type was the most frequent isolated strain, with the M1uk lineage being represented in 6 out of 7 Emm1 isolates in post-pandemic period. M1uk-infected patients were older (median: 67.0 vs. 50.0 years, P=0.073) but mortality was similar. Most patients (86.6%) received β-lactams plus clindamycin. Interestingly, time to clindamycin administration was earlier (median: 1 h vs. 24 h; P <0.050) in the post-pandemic period with a 5-fold increase in ICU mortality (5.6% to 26.5%, OR=6.14, 95% CI: 0.74 to 50.85; P=0.090) among those adults who did not receive clindamycin in the emergency department.

Conclusions: The incidence of iGAS infections requiring ICU admission showed no significant increase post-Coronavirus Disease-19 pandemic. The highly toxigenic M1uk strain became predominant, but it was not associated with worse mortality among adult ICU patients.

Keywords: Antimicrobial stewardship; Clindamycin; Mortality; Soft tissue infections; Streptococcus pyogenes; iGAS incidence.

Figure 1

Number of cases and annual incidence of iGAS infections in Gipuzkoa from January 2010 to May 2024. ICU: Intensive care unit; iGAS: Invasive Group A Streptococcus pyogenes.