title: Rise in Haemophilus influenzae With Reduced Quinolone Susceptibility and Development of a Simple Screening Method.
abstract: β-Lactamase-nonproducing ampicillin-resistant Haemophilus influenzae are prevalent in Japan. Resistance has increased as a consequence of the expanded use of antimicrobial agents, raising concerns about the rise of multidrug (macrolide and fluoroquinolone)-resistant H. influenzae.
  
  
  
  In this study, we investigated susceptibility to fluoroquinolones in H. influenzae clinical isolates from 2013 to 2014 and identified the amino acid substitutions in quinolone resistance-determining regions of gyrA and parC.
  
  
  
  All isolates (n = 145) were susceptible to fluoroquinolones; however, some showed reduced susceptibility. The minimum inhibitory concentration of levofloxacin for these strains was 0.063-0.5 µg/mL, and the strains harbored the amino acid substitution S84L in GyrA. Such strains have seen a significant increase. Importantly, all mutants from 2014 were isolated from pediatric patients. In addition, we developed a simple polymerase chain reaction-based screening method for detecting isolates with reduced fluoroquinolone susceptibility.
  
  
  
  The mutation in GyrA is important as a first step in the development of fluoroquinolone resistance. Hence, detection of reduced susceptible strains may influence the choice of antimicrobial treatment.
authors.affiliation: From the *Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences; †Department of Pediatrics, and ‡Department of Infectious Diseases, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Seyama
authors.forename: Takeaki
authors.initials: T
authors.lastname: Wajima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Nakaminami
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ushio
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.forename: Norihisa
authors.initials: N
authors.lastname: Noguchi
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006192:Haemophilus Infections / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods; D015363:Quinolones / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones