Emergence of Haemophilus influenzae with low susceptibility to quinolones and persistence in tosufloxacin treatment.
Adolescent
Adult
Aged
Aged, 80 and over
Bacterial Proteins
/ genetics
Child
Child, Preschool
DNA Gyrase
/ genetics
Drug Resistance, Multiple, Bacterial
Female
Fluoroquinolones
/ pharmacology
Haemophilus Infections
/ drug therapy
Haemophilus influenzae
/ drug effects
Humans
Infant
Japan
/ epidemiology
Male
Microbial Sensitivity Tests
Middle Aged
Multilocus Sequence Typing
Mutation
Naphthyridines
/ pharmacology
Quinolones
/ pharmacology
Young Adult
Multilocus sequence typing
Quinolone low-susceptible Haemophilus influenzae
Tosufloxacin
Journal
Journal of global antimicrobial resistance
ISSN: 2213-7173
Titre abrégé: J Glob Antimicrob Resist
Pays: Netherlands
ID NLM: 101622459
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
31
10
2018
revised:
08
01
2019
accepted:
11
01
2019
pubmed:
13
2
2019
medline:
17
6
2020
entrez:
13
2
2019
Statut:
ppublish
Résumé
The use of non-β-lactam agents has increased in Japan due to the prevalence of β-lactam-resistant pathogens. This study aimed to clarify the recent trend of antimicrobial susceptibility and molecular epidemiological features in Haemophilus influenzae. Fifty-seven Haemophilus influenzae isolated from a Japanese teaching hospital in 2017 were characterised, and the data were compared with those of a previous study. The MICs were determined using the broth dilution method. Genetic backgrounds were compared by multilocus sequence typing. The bactericidal activity of tosufloxacin at, or near, the therapeutic Cmax was determined in vitro, with susceptible isolates and quinolone low-susceptible isolates by time-kill assay. The results of the susceptibility tests showed that >90% of isolates were susceptible to cephalosporins and carbapenems, whereas ampicillin-susceptible and clarithromycin-susceptible isolates decreased. Regarding quinolones, low-susceptible isolates were noted in 2017, although all isolates were judged as susceptible. All low-susceptible isolates had an amino acid substitution in GyrA, and two isolates had an additional substitution in ParC. These isolates had different genetic backgrounds. Furthermore, the time-kill kinetic assay using the Cmax of tosufloxacin indicated that the low-susceptible isolates could persist for at least 8hours. This study revealed that Haemophilus influenzae has demonstrated multidrug low-susceptibility in recent years. The low-susceptible isolates had genetic diversity, meaning that resistance occurred independently.
Sections du résumé
BACKGROUND
The use of non-β-lactam agents has increased in Japan due to the prevalence of β-lactam-resistant pathogens. This study aimed to clarify the recent trend of antimicrobial susceptibility and molecular epidemiological features in Haemophilus influenzae.
METHODS
Fifty-seven Haemophilus influenzae isolated from a Japanese teaching hospital in 2017 were characterised, and the data were compared with those of a previous study. The MICs were determined using the broth dilution method. Genetic backgrounds were compared by multilocus sequence typing. The bactericidal activity of tosufloxacin at, or near, the therapeutic Cmax was determined in vitro, with susceptible isolates and quinolone low-susceptible isolates by time-kill assay.
RESULTS
The results of the susceptibility tests showed that >90% of isolates were susceptible to cephalosporins and carbapenems, whereas ampicillin-susceptible and clarithromycin-susceptible isolates decreased. Regarding quinolones, low-susceptible isolates were noted in 2017, although all isolates were judged as susceptible. All low-susceptible isolates had an amino acid substitution in GyrA, and two isolates had an additional substitution in ParC. These isolates had different genetic backgrounds. Furthermore, the time-kill kinetic assay using the Cmax of tosufloxacin indicated that the low-susceptible isolates could persist for at least 8hours.
CONCLUSIONS
This study revealed that Haemophilus influenzae has demonstrated multidrug low-susceptibility in recent years. The low-susceptible isolates had genetic diversity, meaning that resistance occurred independently.
Identifiants
pubmed: 30753907
pii: S2213-7165(19)30024-4
doi: 10.1016/j.jgar.2019.01.017
pii:
doi:
Substances chimiques
Bacterial Proteins
0
Fluoroquinolones
0
Naphthyridines
0
Quinolones
0
DNA Gyrase
EC 5.99.1.3
tosufloxacin
GHJ553KQPS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104-108Informations de copyright
Copyright © 2019 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.