Clinical and molecular epidemiological features of critically ill patients with invasive group A Streptococcus infections: a Belgian multicenter case-series

Abstract

Background Recent alerts have highlighted an increase in group A streptococcal (GAS) infections since 2022 in Europe and the United States. Streptococcus pyogenes can cause limited skin or mucosal disease, but can also present as severe invasive disease necessitating critical care. We performed a multicenter retrospective study of patients with GAS infections recently admitted to Belgian intensive care units (ICUs) since January 2022. We describe patient characteristics and investigate the molecular epidemiology of the S. pyogenes strains involved. Results Between January 2022 and May 2023, a total of 86 cases (56 adults, 30 children) with GAS disease were admitted to critical care in the university hospitals of Leuven, Antwerp and Liège. We noted a strikingly high incidence of severe community-acquired pneumonia (sCAP) (45% of adults, 77% of children) complicated with empyema in 45% and 83% of adult and pediatric cases, respectively. Two-thirds of patients with S. pyogenes pneumonia had viral co-infection, with influenza (13 adults, 5 children) predominating. Other disease presentations included necrotizing fasciitis (23% of adults), other severe skin/soft tissue infections (16% of adults, 13% of children) and ear/nose/throat infections (13% of adults, 13% of children). Cardiogenic shock was frequent (36% of adults, 20% of children). Fifty-six patients (65%) had toxic shock syndrome. Organ support requirements were high and included invasive mechanical ventilation (77% of adults, 50% of children), renal replacement therapy (29% of adults, 3% of children) and extracorporeal membrane oxygenation (20% of adults, 7% of children). Mortality was 21% in adults and 3% in children. Genomic analysis of S. pyogenes strains from 55 out of 86 patients showed a predominance of emm1 strains (73%), with a replacement of the M1global lineage by the toxigenic M1UK lineage (83% of emm1 strains were M1UK). Conclusions The recent rise of severe GAS infections (2022–23) is associated with introduction of the M1UK lineage in Belgium, but other factors may be at play—including intense circulation of respiratory viruses and potentially an immune debt after the COVID pandemic. Importantly, critical care physicians should include S. pyogenes as causative pathogen in the differential diagnosis of sCAP.

Molecular epidemiology of invasive Group A Streptococcal infections before and after the COVID-19 pandemic in Switzerland

“…Accordingly, we observed that in our cohort emm1/ST28 was the predominant variant, present in most patients (5/7) who died from an iGAS infection. Interestingly, we did not find any clusters originating from the three reference strains refM1uk, ref5005 and ref5448, known to cause invasive infections [9,37,38]. Furthermore, the phenotypic susceptibility testing revealed a high susceptibility to penicillin, erythromycin and clindamycin, confirming the known susceptibility patterns over the years without a shift towards more resistant strains, as reported worldwide [4,6,9].…”

“…The current hypothesis suggests that the lack of exposure to GAS and common seasonal respiratory viruses during the COVID-19 pandemic, due to isolation measures, resulted in decreased immunity to GAS and seasonal respiratory viruses [35, 37, 43, 45]. After lifting the COVID-19 pandemic protection measures, an increase and a shift of the seasonal pattern in seasonal respiratory viral and iGAS infections was observed after two years of their historically low incidence.…”