Etiology of Acute Otitis Media and Characterization of Pneumococcal Isolates After Introduction of 13-Valent Pneumococcal Conjugate Vaccine in Japanese Children

Background: Acute otitis media is a leading cause of childhood morbidity and antibiotic prescriptions. We examined etiologic changes in acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine as routine immunization for Japanese children in 2014. Serotypes, resistance genotypes, antibiotic susceptibilities and multilocus sequence typing of pneumococcal isolates were also characterized. Methods: Otolaryngologists prospectively collected middle ear fluid from 582 children by tympanocentesis or sampling through a spontaneously ruptured tympanic membrane between June 2016 and January 2017. Causative pathogens were identified by bacterial culture and real-time polymerase chain reaction for bacteria. Serotypes, resistance genotypes, sequence types and susceptibilities to 14 antimicrobial agents were determined for pneumococcal isolates. Results: At least 1 bacterial pathogen was identified in 473 of the samples (81.3%). Nontypeable Haemophilus influenzae (54.8%) was detected most frequently, followed by Streptococcus pneumoniae (25.4%), Streptococcus pyogenes (2.9%) and others. Pneumococci of current vaccine serotypes have decreased dramatically from 82.1% in 2006 to 18.5% (P < 0.001). Commonest serotypes were 15A (14.8%), 3 (13.9%) and 35B (11.1%). Serotype 3 was significantly less frequent among children receiving 13-valent pneumococcal conjugate vaccine compared with 7-valent pneumococcal conjugate vaccine (P = 0.002). Genotypic penicillin-resistant S. pneumoniae accounted for 28.7%, slightly less than in 2006 (34.2%; P = 0.393); the penicillin-resistant serotypes 15A and 35B had increased. Serotypes 15A, 3 and 35B most often belonged to sequence types 63, 180 and 558. Conclusions: Our findings are expected to assist in development of future vaccines, and they underscore the need for appropriate clinical choice of oral agents based on testing of causative pathogens.