Abstract
In our community-based prospective cohort study in young children, we observed a significant increase in pneumococcal serotype 35B nasopharyngeal (NP) commensal colonization during the 2011–2014 timeframe, but these strains were not associated with disease. Beginning in 2015 and continuing through to the present, the serotype 35B virulence changed, and it became the dominant bacteria isolated and associated with pneumococcal acute otitis-media (AOM) in our cohort. We performed comparative analyses of 250 35B isolates obtained from 140 children collected between 2006 and 2019. Changes in prevalence, clonal-complex composition, and antibiotic resistance were analyzed. Seventy-two (29%) of 35B isolates underwent whole-genome sequencing to investigate genomic changes associated with the shift in virulence that resulted in increased rates of 35B-associated AOM disease. 35B strains that were commensals and AOM disease-causing were mainly associated with sequence type (ST) 558. Antibiotic concentrations of β-lactams and ofloxacin necessary to inhibit growth of 35B strains rose significantly (2006–2019) (p<0.005). However, only isolates from the 35B/ST558 showed significant increases in MIC50 of penicillin and ofloxacin between the years 2006–2014 and 2015–2019 (p=0.007 and p<0.0001). One hundred thirty-eight SNPs located in 34 different genes were significantly associated with post-2015 strains. SNPs were found in nrdG (metal binding, 10%); metP and metN (ABC transporter, 9%); corA (Mg2+ transporter, 6%); priA (DNA replication, 5%); and on the enzymic gene ldcB (LD-carboxypeptidase, 3%). Pneumococcal serotype 35B strains was a common NP commensal during 2010–2014. In 2015, a shift in increasing number of AOM cases occurred in young children caused by 35B, that was associated with changes in genetic composition and antibiotic susceptibility.
Highlights
Streptococcus pneumoniae (SPN) is a common bacterial cause of non-bacteremic pneumonia, sinusitis, otitis media, bacteremia, and meningitis (McCoy and Pettigrew, 2003; Bradley et al, 2011; Mufson et al, 2012)
After implementation of PCV-13 in 2010, we reported that serotype 35B SPN became one of the most frequent colonizers in young children (Kaur et al, 2016)
We re-examined 250 serotype 35B isolates that had been collected from children (18.6% of enrolled children) during 2006 to 2019
Summary
Streptococcus pneumoniae (SPN) is a common bacterial cause of non-bacteremic pneumonia, sinusitis, otitis media, bacteremia, and meningitis (McCoy and Pettigrew, 2003; Bradley et al, 2011; Mufson et al, 2012). Et al, 2007; Pilishvili et al, 2010), strains expressing serotypes not included in the vaccines have emerged as replacements to colonize the NP and cause disease (Cohen et al, 2015; Kaur et al, 2016; Yildirim et al, 2017; Pichichero et al, 2018). After implementation of PCV-13 in 2010, we reported that serotype 35B SPN became one of the most frequent colonizers in young children (Kaur et al, 2016). Serotype 35B became the most commonly detected serotype among asymptomatically colonized young children and the most common cause of AOM during 2015–2019 (Kaur et al, EJCMID, pending revisions). The objective was to describe dynamics of circulation of serotype 35B and understand the genetic changes associated with the emergence of a more virulent serotype 35B that was associated with pediatric disease
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