Abstract
SummaryBackgroundPneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation.MethodsWe did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole–trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product.FindingsFrom 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6–14·4), sulfamethoxazole–trimethoprim (9·7%, 4·3–15·2), and third-generation cephalosporins (7·5%, 3·1–11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3–9·4), sulfamethoxazole–trimethoprim (16·0%, 11·0–21·2), third-generation cephalosporins (4·5%, 0·3–8·7), macrolides (3·6%, 0·7–6·6) and tetracycline (2·0%, 0·3–3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible.InterpretationImplementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements.FundingBill & Melinda Gates Foundation.
Highlights
Streptococcus pneumoniae causes clinical conditions encompassing upper respiratory infections such as otitis media and sinusitis, non-bacteraemic pneu monia, and severe invasive diseases such as bacteraemic pneumonia, sepsis, and meningitis.[1]
Serotypes included in the first-generation 7-valent conjugate vaccine (PCV7) were 12·5-times as likely as non-PCV7 serotypes to show diminished susceptibility to penicillin in the USA, and accounted for 79% of penicillin-non-susceptible invasive pneumococcal disease www.thelancet.com/microbe Vol 2 September 2021
It is uncertain to what extent these patterns were reflected in other settings, and whether changes in susceptibility of circulating pneumococci are causally attributable to the implementation of pneumococcal conjugate vaccine (PCV) rather than secular trends
Summary
Streptococcus pneumoniae (pneumococcus) causes clinical conditions encompassing upper respiratory infections such as otitis media and sinusitis, non-bacteraemic pneu monia, and severe invasive diseases such as bacteraemic pneumonia, sepsis, and meningitis.[1]. The search string of our systematic review revealed no previous reviews synthesising data from multiple settings on the effect of pneumococcal conjugate vaccines (PCVs) on the distribution of antimicrobial susceptibility and resistance in circulating Streptococcus pneumoniae. Before PCV implementation, surveillance studies of pneumococcal carriage and invasive pneumococcal disease (IPD) revealed that PCV-targeted serotypes were more probable than non-vaccine serotypes to harbour lineages with diminished susceptibility or resistance to commonly-used antimicrobial drugs. Several multiyear surveillance studies of pneumococcal carriage and IPD, predominantly done in high-income settings, revealed increases in the proportion of non-vaccine-serotype pneumococci with reduced susceptibility or resistance to penicillin and macrolides. It is uncertain to what extent these patterns were reflected in other settings, and whether changes in susceptibility of circulating pneumococci are causally attributable to the implementation of PCVs rather than secular trends
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