Genetic characteristics and antibiotic resistance of Haemophilus influenzae isolates from pediatric patients with acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine in Japan

The AOM Surveillance Study Group

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Acute otitis media (AOM) occurs commonly in pediatric populations. We examined resistance genotype, antibiotic susceptibility, quinolone (QL) resistance, and multilocus sequence type (MLST) among Haemophilus influenzae isolates causing AOM following introduction of pneumococcal conjugate vaccines in Japan. The AOM surveillance group included 69 participating otolaryngologists. Causative pathogens isolated from middle ear fluid (MEF) samples collected from 582 children with AOM were identified using both bacterial culture and real-time PCR. H. influenzae isolates among these pathogens were characterized by capsular type, resistance genotype, antibiotic susceptibility, QL resistance, and MLST. In 2016, H. influenzae was identified in 319 samples (54.8%), among which 72.4% (n = 231) tested positive by both culture and PCR; remaining H. influenzae cases were only PCR-positive. This proportion of H. influenzae positivity has increased significantly from 41.2% in 2006 (p < 0.001). Among culture-positive strains, genotypic β-lactamase-nonproducing ampicillin (AMP)-resistant (gBLNAR) strains were frequent (63.2%), with β-lactamase-nonproducing AMP-susceptible (gBLNAS) strains accounting for only 24.2%. Susceptibilities of gBLNAR to oral antimicrobials were best for tosufloxacin, followed by cefditoren and tebipenem; MIC90s were 0.031 μg/mL, 0.5 μg/mL, and 1 μg/mL, respectively. In 7 gBLNAR isolates (3.0%), QL susceptibility was low, owing to amino acid substitutions in GyrA and/or ParC. Sequence types identified numbered 107, including 28 that were new. Prevention of further increases in resistance to antimicrobial agents will require antibiotic selection based on characterization of causative pathogens in clinical practice.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalJournal of Infection and Chemotherapy
Issue number9
Publication statusPublished - 2019 Sep



  • Acute otitis media
  • Genotypic resistance
  • Haemophilus influenzae
  • Multilocus sequence typing
  • Quinolone resistance
  • gBLNAR

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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