title: Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009.
abstract: BACKGROUND
  Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes.
  
  
  METHODS
  All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis.
  
  
  RESULTS
  A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes (< 40 isolates each). Over time, there has been a decreasing trend for PCV7 serotypes (R(2) = 0.944; p < 0.001, with significant decreasing trends for serotypes 19F, 14, 23F and 9V), and increasing trends for serotype 19A (R(2) = 0.901; p < 0.001), serotype 3 (R(2) = 0.463; p = 0.030) and other non-PCV7 serotypes (R(2) = 0.877; p < 0.001), but not for serotype 6A (R(2) = 0.311; p = 0.094). Considering all isolates, amoxicillin non-susceptibility showed an increasing trend (R(2) = 0.528; p = 0.017). Regarding serotype 19A, increasing trends in non-susceptibility to penicillin (R(2) = 0.726; p = 0.001), amoxicillin (R(2) = 0.804; p < 0.001), cefotaxime (R(2) = 0.546; p = 0.005) and erythromycin (R(2) = 0.546; p = 0.009) were found, with amoxicillin non-susceptibility firstly detected in 2003 (7.4%) and increasing up to 38.0% in 2009. In PCV7 serotypes (which prevalence decreased from 70.7% during 1997-2000 to 10.6% in 2009) amoxicillin non-susceptibility rates showed an increasing trend (R(2) = 0.702; p = 0.002). However, overall, amoxicillin non-susceptibility (≈25% in 2008-9) could be mainly attributed to serotype 19A (> 35% isolates) since PCV7 strains represented < 11% of total clinical isolates.
  
  
  CONCLUSIONS
  In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.
authors.affiliation: Spanish Reference Pneumococcal Laboratory, Inst. Salud Carlos III, ctra. Majadahonda-Pozuelo Km. 2, 28220 Majadahonda, Madrid, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Fenoll
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Aguilar
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Vicioso
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Gimenez
authors.forename: Olga
authors.initials: O
authors.lastname: Robledo
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Granizo
mesh_terms: D000293:Adolescent; D000658:Amoxicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D007223:Infant; D008826:Microbial Sensitivity Tests; D010034:Otitis Media with Effusion / Q000453:epidemiology* / Q000382:microbiology; D010406:Penicillins / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D015995:Prevalence; D012703:Serotyping; D013030:Spain / Q000453:epidemiology; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D004917:Erythromycin; D000658:Amoxicillin