Clinical and Bacteriologic Analysis of Nontypeable Haemophilus influenzae Strains Isolated from Children with Invasive Diseases in Japan from 2008 to 2015

J Clin Microbiol. 2018 Jun 25;56(7):e00141-18. doi: 10.1128/JCM.00141-18. Print 2018 Jul.

Abstract

Haemophilus influenzae type b (Hib) conjugate vaccines have led to dramatic reductions in Hib disease among young children worldwide. Nontypeable H. influenzae (NTHi) is now the major cause of invasive H. influenzae infections. We investigated the clinical characteristics of invasive NTHi diseases among children in Japan, to clarify the pathogenicity of isolated NTHi strains. The mortality rate was 10.7%, with deaths occurring mainly among children with underlying comorbidities. Biotypes II and III were the most common, and most strains (64.3%) had multiple amino acid substitutions at the Asp-350, Ser-357, Ser-385, and/or Met-377 sites of penicillin-binding protein 3. Two strains were β-lactamase positive and ampicillin-clavulanate resistant. Biofilm indices varied widely, and IS1016 was detected in 10.7% of the strains tested. Moreover, there was wide variation in the characteristics of invasive NTHi strains. NTHi strains, showing great genetic diversity, are responsible for most invasive H. influenzae infections in children in the postvaccine era. Continuous monitoring of NTHi strains responsible for invasive diseases in children is important to detect changes in the epidemiology of invasive H. influenzae infections in the postvaccine era.

Keywords: Japan; children; epidemiology; infection; invasive disease; nontypeable Haemophilus influenzae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Adhesion / genetics
  • Bacterial Typing Techniques
  • Biofilms / growth & development
  • Child
  • Child, Preschool
  • DNA Transposable Elements
  • Drug Resistance, Bacterial / genetics
  • Genetic Variation
  • Genome, Bacterial / genetics
  • Haemophilus Infections / epidemiology
  • Haemophilus Infections / microbiology*
  • Haemophilus Infections / mortality
  • Haemophilus Infections / physiopathology
  • Haemophilus influenzae / classification*
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / genetics
  • Haemophilus influenzae / physiology*
  • Humans
  • Infant
  • Infant, Newborn
  • Japan / epidemiology
  • Microbial Sensitivity Tests
  • Sequence Analysis, DNA

Substances

  • Anti-Bacterial Agents
  • DNA Transposable Elements