Population genetic structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in children in Argentina

Abstract

Invasive disease caused by Streptococcus pneumoniae (IPD) is one of the leading causes of morbidity and mortality in young children worldwide. In Argentina, PCV13 was introduced into the childhood immunization programme nationwide in 2012 and PCV7 was available from 2000, but only in the private market. Since 1993 the National IPD Surveillance Programme, consisting of 150 hospitals, has conducted nationwide pneumococcal surveillance in Argentina in children under 6 years of age, as part of the SIREVA II-OPS network. A total of 1713 pneumococcal isolates characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, belonging to three study periods: pre-PCV7 era 1998–1999 (pre-PCV), before the introduction of PCV13 2010–2011 (PCV7) and after the introduction of PCV13 2012–2013 (PCV13), were available for inclusion. Fifty-four serotypes were identified in the entire collection and serotypes 14, 5 and 1 represented 50% of the isolates. Resistance to penicillin was 34.9%, cefotaxime 10.6%, meropenem 4.9%, cotrimoxazole 45%, erythromycin 21.5%, tetracycline 15.4% and chloramphenicol 0.4%. All the isolates were susceptible to levofloxacin, rifampin and vancomycin. Of 1713 isolates, 1061 (61.9%) were non-susceptible to at least one antibiotic and 235(13.7%) were multidrug resistant. A subset of 413 isolates was randomly selected and whole-genome sequenced as part of Global Pneumococcal Sequencing Project (GPS). The genome data was used to investigate the population structure of S. pneumoniae defining pneumococcal lineages using Global Pneumococ-cal Sequence Clusters (GPSCs), sequence types (STs) and clonal complexes (CCs), prevalent serotypes and their associated pneumococcal lineages and genomic inference of antimicrobial resistance. The collection showed a great diversity of strains. Among the 413 isolates, 73 known and 36 new STs were identified belonging to 38 CCs and 25 singletons, grouped into 52 GPSCs. Important changes were observed among vaccine types when pre-PCV and PCV13 periods were compared; a significant decrease in serotypes 14, 6B and 19F and a significant increase in 7F and 3. Among non-PCV13 types, serogroup 24 increased from 0% in pre-PCV to 3.2% in the PCV13 period. Our analysis showed that 66.1% (273/413) of the isolates were predicted to be non-susceptible to at least one antibiotic and 11.9% (49/413) were multidrug resistant. We found an agreement of 100% when comparing the serotype determined by Quellung and WGS-based serotyping and 98.4% of agreement in antimicrobial resistance. Continued surveillance of the pneumococcal population is needed to reveal the dynamics of pneumococcal isolates in Argentina in post-PCV13. This article contains data hosted by Microreact.