Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations

Pierre Robert Smeesters (1, 2) , Anne Vergison (2, 3) , Dioclécio Campos Junior (4) , Laurence van Melderen (1)

1 Service Evolution Biologique et Ecologie -Faculté des Sciences
2 Infectious Diseases Department
3 ULB - Département d'Informatique [Bruxelles]
4 Pediatric Department

Clonal emergence of group A streptococci (GAS) with reduced susceptibility to fluoroquinolones (FQs) has been increasingly reported. Non-susceptibility is associated with various point mutations in the target-encoding genes and has only been described in a few types. We used a well characterised GAS clinical paediatric collection from Brussels (Belgium) and Brasília (Brazil) to analyse the molecular basis of FQ non-susceptibility. GAS strains were tested for ciprofloxacin susceptibility and were screened for mutations in DNA gyrase- and topoisomerase IV-encoding genes. Genetic relationships between the different types were assessed by phylogenetic analysis of the whole surface-exposed part of the M protein. A high proportion (22.5%) of ciprofloxacin-non-susceptible isolates (minimal inhibitory concentration ≥ 2mg/L) was found among the Belgian strains. They belonged mostly to type 6 (87%). In Brazil, 6% of the isolates, belonging to seven distantly related types, were non-susceptible. Our phylogenetic analysis showed that non-susceptibility may arise in various genetic backgrounds. Sequence comparison of the quinolone resistance-determining regions (QRDRs) of the ParC- and ParE-encoding genes from susceptible and non-susceptible isolates revealed that most of the mutations were found in both classes of isolates, indicating an type-linked polymorphism. In conclusion, we observed a clonal spreading of non-susceptible type 6 GAS strains in Brussels and a polyclonal distribution of non-susceptible isolates in Brazil. All the Brazilian and Belgian type 6 strains displayed a S79A/F mutation in that convincingly explains the non-susceptible phenotype.

Mots clés: Quinolone resistance; Epidemiology; Antimicrobial resistance mechanisms; Point mutations

Pierre Robert Smeesters, Anne Vergison, Dioclécio Campos Junior, Laurence van Melderen. Emerging fluoroquinolone-non-susceptible group A streptococci in two different paediatric populations. International Journal of Antimicrobial Agents, 2009, 34 (1), pp.44. ⟨10.1016/j.ijantimicag.2009.01.012⟩. ⟨hal-00556328⟩