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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Abstract

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; MIC 90 s 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
JournalJournal of Infection and Chemotherapy
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Conjugate Vaccines
Haemophilus influenzae
Otitis Media
Microbial Drug Resistance
Japan
Pediatrics
Quinolones
tosufloxacin
Ampicillin
Genotype
Polymerase Chain Reaction
Pneumococcal Vaccines
Middle Ear
Amino Acid Substitution
Anti-Infective Agents
Real-Time Polymerase Chain Reaction
13-valent pneumococcal vaccine
Anti-Bacterial Agents
Population

Keywords

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

ASJC Scopus subject areas

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

Cite this

@article{d9ccee332184437581de1c3facb8874a,
title = "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",
abstract = "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; MIC 90 s 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.",
keywords = "Acute otitis media, gBLNAR, Genotypic resistance, Haemophilus influenzae, Multilocus sequence typing, Quinolone resistance",
author = "{The AOM Surveillance Study Group} and Kimiko Ubukata and Miyuki Morozumi and Megumi Sakuma and Yoko Adachi and Eriko Mokuno and Takeshi Tajima and Satoshi Iwata and Mikiya Inagaki and Kiyoaki Kamakazu and Yoshihiro Atago and Shinichi Kakurai and Junichi Iwamoto and Shinji Usui and Seizou Ooyama and Sumio Sugano and Hisashi Kuroda and Yousuke Kamide and Michihiro Kamide and Yasuko Murakawa and Satoru Kaieda and Ippei Kawaziri and Akimitsu Kawai and Yasutake Kikuchi and Seiji Sawaki and Koujin Kyou and Shigeru Kimura and Yasuko Kimura and Yutaka Kimura and Hideyuki Sashiyou and Hirohide Yoneya and Kazumi Kosaka and Mototane Komeda and Katsuhiko Kobayashi and Yudzuru Sakaida and Shoichi Sawada and Tatsuaki Satoh and Masami Satoh and Toshiaki Shimizu and Osamu Kimura and Jun Shimada and Yasutaka Hori and Rinya Sugita and Yoshinobu Sugita and Akihiro Uchizono and Kazuhiro Soeda and Tomizou Tabuchi and Chiharu Matsuoka and Chiaki Suzuki and Hideki Chiba and Yasuhiro Tsuboi",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jiac.2019.03.019",
language = "English",
journal = "Journal of Infection and Chemotherapy",
issn = "1341-321X",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - 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

AU - The AOM Surveillance Study Group

AU - Ubukata, Kimiko

AU - Morozumi, Miyuki

AU - Sakuma, Megumi

AU - Adachi, Yoko

AU - Mokuno, Eriko

AU - Tajima, Takeshi

AU - Iwata, Satoshi

AU - Inagaki, Mikiya

AU - Kamakazu, Kiyoaki

AU - Atago, Yoshihiro

AU - Kakurai, Shinichi

AU - Iwamoto, Junichi

AU - Usui, Shinji

AU - Ooyama, Seizou

AU - Sugano, Sumio

AU - Kuroda, Hisashi

AU - Kamide, Yousuke

AU - Kamide, Michihiro

AU - Murakawa, Yasuko

AU - Kaieda, Satoru

AU - Kawaziri, Ippei

AU - Kawai, Akimitsu

AU - Kikuchi, Yasutake

AU - Sawaki, Seiji

AU - Kyou, Koujin

AU - Kimura, Shigeru

AU - Kimura, Yasuko

AU - Kimura, Yutaka

AU - Sashiyou, Hideyuki

AU - Yoneya, Hirohide

AU - Kosaka, Kazumi

AU - Komeda, Mototane

AU - Kobayashi, Katsuhiko

AU - Sakaida, Yudzuru

AU - Sawada, Shoichi

AU - Satoh, Tatsuaki

AU - Satoh, Masami

AU - Shimizu, Toshiaki

AU - Kimura, Osamu

AU - Shimada, Jun

AU - Hori, Yasutaka

AU - Sugita, Rinya

AU - Sugita, Yoshinobu

AU - Uchizono, Akihiro

AU - Soeda, Kazuhiro

AU - Tabuchi, Tomizou

AU - Matsuoka, Chiharu

AU - Suzuki, Chiaki

AU - Chiba, Hideki

AU - Tsuboi, Yasuhiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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; MIC 90 s 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.

AB - 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; MIC 90 s 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.

KW - Acute otitis media

KW - gBLNAR

KW - Genotypic resistance

KW - Haemophilus influenzae

KW - Multilocus sequence typing

KW - Quinolone resistance

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U2 - 10.1016/j.jiac.2019.03.019

DO - 10.1016/j.jiac.2019.03.019

M3 - Article

AN - SCOPUS:85064161519

JO - Journal of Infection and Chemotherapy

JF - Journal of Infection and Chemotherapy

SN - 1341-321X

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