Abstract
Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013–2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.
Highlights
Taiwan launched a national vaccination catch-up program in 2013, in which 1 dose of 13-valent PCV (PCV13) was administered to children 24–60 months of age
We examined the in vitro activity of penicillin and meropenem against invasive pneumococcal strains isolated in Taiwan during 2013–2017, analyzed their genetic relatedness, and assessed the role of amino acid changes in PBP1a, 2b, and 2x in meropenem resistance
Since 2006, Chang Gung Memorial Hospital (CGMH) has archived all pneumococcal isolates from patients with invasive pneumococcal disease (IPD), which was defined as an illness in which S. pneumoniae was isolated from >1 normally sterile site
Summary
Taiwan launched a national vaccination catch-up program in 2013, in which 1 dose of 13-valent PCV (PCV13) was administered to children 24–60 months of age. Meropenem resistance seen in the S. pneumoniae 15A-ST63 clone in Japan was thought to be due to acquisition of penicillin-binding protein (PBP) 1a (type 13) via recombination with a formerly predominant global serotype 19A-ST320 vaccine strain [3]. RESEARCH (PMEN) standardized nomenclature of prevalent multidrug-resistant international clones causing most invasive diseases, including Spain23F-ST81 (PMEN1), Taiwan19F-ST236 (PMEN14), Taiwan23FST242 (PMEN15), and 19A-ST320 [9,10]. These clones usually harbored PBPs that are not susceptible to penicillins, third-generation cephalosporins, and meropenem [3,11]. We used whole-genome sequencing (WGS) to characterize the prevalent clone and its relationship to historical strains
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