Clinical, microbiological, and molecular characterization of pediatric invasive infections by
Streptococcus pyogenes
in Spain in a context of global outbreak
Authors: Ramírez de Arellano Eva , Saavedra-Lozano Jesús , Villalón Pilar , Jové-Blanco Ana , Grandioso David , Sotelo Jared , Gamell Anna , González-López Juan José , Cervantes Eloísa , Gónzalez María José , Rello-Saltor Victoria , Esteva Cristina , Sanz-Santaeufemia Francisco , Yagüe Genoveva , Manzanares Ángela , Brañas Patricia , Ruiz de Gopegui Enrique , Carrasco-Colom Jaime , García Federico , Cercenado Emilia , Mellado Isabel , del Castillo Elena , Pérez-Vazquez María , Oteo-Iglesias Jesús , Calvo Cristina ,   on behalf of the Spanish PedGAS-Net/CIBERINFEC GAS Study Group
Published: March 2024

ABSTRACT

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of
Streptococcus pyogenes
infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A
Streptococcus
invasive infections (iGAS) in children prospectively recruited in Spain (September 2022–March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of
S. pyogenes
causing infection (102 iGAS and 28 mild infections) were included in the microbiological study:
emm
typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to
emm
1 and
emm
12;
emm
12 predominated in 2022 but was surpassed by
emm
1 in 2023. Spread of M1
UK
sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1
global
(36/64). Furthermore, a difference in
emm
types compared with the mild cases was observed with predominance of
emm
1, but also important representativeness of
emm
12 and
emm
89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the
spe
A gene, while the
ssa
superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/
emm
1, ST36-ST425/
emm
12, ST242/
emm
12.37, ST39/
emm
4, and ST101-ST1295/
emm
89 isolates.

IMPORTANCE

Group A
Streptococcus
(GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an
emm
types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.