title: Trends in antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharyngeal flora in children with acute otitis media in France before and after 13 valent pneumococcal conjugate vaccine introduction.
abstract: BACKGROUND
  After the implementation of pneumococcal conjugate vaccines (PCVs), the marked shift in Streptococcus pneumoniae (Pnc) serotype distribution led to a modification in pneumococcal antibiotic susceptibility. In 2011, the pattern of antibiotic prescription in France for acute otitis media in infants was greatly modified, with decreased use of third-generation cephalosporins and amoxicillin-clavulanate replaced by amoxicillin alone. To assess antibiotic strategies, here we measured the antibiotic susceptibility of Pnc and Haemophilus influenzae (Hi) isolated from nasopharyngeal flora in infants with acute otitis media in the 13-valent PCV (PCV13) era in France.
  
  
  METHODS
  From November 2006 to June 2013, 77 pediatricians obtained nasopharyngeal swabs from infants (6 to 24 months old) with acute otitis media. The swabs were sent for analysis to the national reference centre for pneumococci in France. Demographics, medical history, and physical examination findings were recorded.
  
  
  RESULTS
  We examined data for 7200 children, 3498 in the pre-PCV13 period (2006-2009) and 3702 in the post-PCV13 period (2010-2013). The Pnc carriage rate decreased from 57.9% to 54.2% between the 2 periods, and the proportion of pneumococcal strains with reduced susceptibility to penicillin or resistant to penicillin decreased from 47.1% to 39% (P < 0.0001). The Hi carriage rate increased from 48.2% to 52.4%, with the proportion of ß-lactamase-producing strains decreasing from 17.1% to 11.9% and the proportion of ß-lactamase-nonproducing, ampicillin-resistant strains remaining stable, from 7.7% to 8.2%. We did not identify any risk factor associated with carriage of ß-lactamase-producing Hi strains (such as daycare center attendance, otitis-prone condition or recent antibiotic use).
  
  
  CONCLUSIONS
  In France, the nasopharyngeal carriage rate of reduced-susceptibility pneumococcal strains and ß-lactamase-producing Hi strains decreased in children with acute otitis media after 2010, the year the PCV13 was introduced. Accordingly, amoxicillin as the first-line drug for acute otitis media requiring antibiotics remains a valid choice.
authors.affiliation: Service d'Accueil des Urgences Pédiatriques, AP-HP, Hôpital Necker-Enfants-Malades, Université Paris Descartes Sorbonne Paris Cité, ECEVE - INSERM UMR1123, Paris, France. francois.angoulvant@nck.aphp.fr.
authors.forename: François
authors.initials: F
authors.lastname: Angoulvant
authors.affiliation: ACTIV, Association Clinique et Thérapeutique Infantile du Val de Marne, Saint-Maur des Fossés, France. robert.cohen@wanadoo.fr.|Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, France. robert.cohen@wanadoo.fr.|Unité Court Séjour, Petits Nourrissons, Service de Néonatologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France. robert.cohen@wanadoo.fr.|AFPA, Association Française de Pédiatrie Ambulatoire, Chambéry, France. robert.cohen@wanadoo.fr.
authors.forename: Robert
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Université Paris Diderot Sorbonne Paris Cité, Paris, France. catherine.doit@rdb.aphp.fr.|Service de Microbiologie, AP-HP, Hôpital Robert-Debré, 75019, Paris, France. catherine.doit@rdb.aphp.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Doit
authors.affiliation: ACTIV, Association Clinique et Thérapeutique Infantile du Val de Marne, Saint-Maur des Fossés, France. active@activ-france.fr.
authors.forename: Annie
authors.initials: A
authors.lastname: Elbez
authors.affiliation: AFPA, Association Française de Pédiatrie Ambulatoire, Chambéry, France. docteur.werner.pediatre@wanadoo.fr.
authors.forename: Andreas
authors.initials: A
authors.lastname: Werner
authors.affiliation: ACTIV, Association Clinique et Thérapeutique Infantile du Val de Marne, Saint-Maur des Fossés, France. stephane.bechet@activfrance.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Béchet
authors.affiliation: Université Paris Diderot Sorbonne Paris Cité, Paris, France. stephane.bonacorsi@rdb.aphp.fr.|Service de Microbiologie, AP-HP, Hôpital Robert-Debré, 75019, Paris, France. stephane.bonacorsi@rdb.aphp.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bonacorsi
authors.affiliation: National Reference Center for Pneumococci, Laboratoire de Microbiologie, AP-HP, Hopital Européen Georges-Pompidou, Paris, France. emmanuelle.varon@egp.aphp.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Varon
authors.affiliation: ACTIV, Association Clinique et Thérapeutique Infantile du Val de Marne, Saint-Maur des Fossés, France. corinne.levy@activ-france.fr.|Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, France. corinne.levy@activ-france.fr.|AFPA, Association Française de Pédiatrie Ambulatoire, Chambéry, France. corinne.levy@activ-france.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Levy
mesh_terms: D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D005260:Female; D005602:France; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D010033:Otitis Media / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D001618:beta-Lactamases / Q000187:drug effects
chemical_list: C538862:13-valent pneumococcal vaccine; D000900:Anti-Bacterial Agents; D022242:Pneumococcal Vaccines; D001618:beta-Lactamases