#Pneumococcal susceptibility to #antibiotics in #carriage: a 17 year time series analysis of the adaptive #evolution of non-vaccine emerging #serotypes to a new selective pressure environment (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment

Naim Ouldali, Robert Cohen, Corinne Levy, Nathalie Gelbert-Baudino, Elisa Seror. François Corrard, François Vie Le Sage, Anne-Sylvestre Michot, Olivier Romain, Stéphane Bechet, Stéphane Bonacorsi, François Angoulvant, Emmanuelle Varon

Journal of Antimicrobial Chemotherapy, dkz281, https://doi.org/10.1093/jac/dkz281

Published: 06 July 2019

 

Abstract

Background

Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption.

Objectives

To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations.

Methods

We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression.

Results

We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (−0.5% per month; 95% CI −0.9 to −0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (−22.2%; 95% CI −33.0 to −11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence.

Conclusions

In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Penicillin; Streptococcus pneumoniae; Vaccines; Haemophilus Influenzae.

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Interaction with nontypeable #Haemophilus influenzae alters progression of #Streptococcus pneumoniae serotypes from colonization to upper #respiratory tract #diseases in #children in a site-specific manner (J Infect dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Interaction with nontypeable Haemophilus influenzae alters progression of Streptococcus pneumoniae serotypes from colonization to upper respiratory tract diseases in children in a site-specific manner

Joseph A Lewnard, Noga Givon-Lavi, Ron Dagan

The Journal of Infectious Diseases, jiz312, https://doi.org/10.1093/infdis/jiz312

Published: 22 June 2019

 

Abstract

Introduction

Pneumococci and nontypeable Haemophilusinfluenzae (NTHi) often co-colonize children. The impact of species interactions on disease risk across the upper respiratory mucosa is not known.

Methods

We analyzed data from 4,104 acute conjunctivitis (AC) cases, 11,767 otitis media (OM) cases, and 1,587 nasopharyngeal specimens collected from Israeli children before pneumococcal conjugate vaccine introduction. We compared pneumococcal serotype distributions with NTHi present and absent, and compared single-species and mixed-species rates of serotype-specific progression from colonization to AC and OM.

Results

Pneumococcal serotypes causing single-species OM (NTHi absent) were less diverse than colonizing serotypes, and also less diverse than those causing mixed-species OM; colonizing and OM-causing pneumococcal serotype distributions were more similar to each other with NTHi present than with NTHi absent. In contrast, serotype diversity did not differ appreciably between colonizing and AC-causing pneumococci, regardless of NTHi co-occurrence. The similarity of colonizing and AC-causing pneumococcal serotype distributions was consistent in the presence and absence of NTHi. Differences in rates that pneumococcal serotypes progressed from colonization to disease were reduced in both AC and OM when NTHi was present.

Conclusions

Interactions with NTHi may alter progression of pneumococcal serotypes to diseases of the upper respiratory mucosa in a site-specific manner.

Streptococcus pneumoniae, nontypeable Haemophilus influenzae, otitis media, acute connunctivitis, nasopharynx, carriage

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Haemophilus Influenzae; Streptococcus pneumoniae; Pediatrics.

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Acquisition of #betalactamase by #Neisseria meningitidis through possible horizontal #gene transfer (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Acquisition of beta-lactamase by Neisseria meningitidis through possible horizontal gene transfer

Eva Hong, Ala-Eddine Deghmane and Muhamed-Kheir Taha#

Author Affiliations: Invasive Bacterial Infection and National Reference Centre for meningococci, Institut Pasteur, Paris, France

 

ABSTRACT

We report the detection in France of a beta-lactamase producing invasive meningococcal isolate. Whole genome sequencing of the isolate revealed ROB-1 type beta-lactamase gene that is frequently encountered in Haemophilus influenzae suggesting horizontal transfer between isolates of these bacterial species. Beta-lactamases are exceptional in meningococci with no reports from more than two decades. This report is worrying as the expansion of such isolates may jeopardize the effective treatment against invasive meningococcal disease.

 

FOOTNOTES

#For correspondence: Email mktaha@pasteur.fr, Tel +33 1 45 68 84 38, Fax +33 1 45 68 83 38

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; France; Neisseria meningitidis; Haemophilus influenzae.

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#Carbapenem-non-Susceptible #Haemophilus influenzae with #Penicillin-Binding Protein 3 containing Amino Acid Insertion (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Carbapenem-non-Susceptible Haemophilus influenzae with Penicillin-Binding Protein 3 containing Amino Acid Insertion

Kazuki Kitaoka a, Kouji Kimura a#, Hiromitsu Kitanaka a, Hirotsugu Banno a, Wanchun Jin a, Jun-ichi Wachino a and Yoshichika Arakawa a

Author Affiliations: a Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan

 

ABSTRACT

Prevalence of β-lactamase-negative ampicillin-resistant Haemophilus influenzae(BLNAR) has become a clinical concern. In BLNAR, amino acid substitutions in penicillin-binding protein 3 (PBP3) are relevant to the β-lactam resistance. Carbapenem-non-susceptible H. influenzae isolates have been rarely reported. Through antimicrobial susceptibility testing and nucleotide sequence analysis of ftsI, encoding PBP3, and utilizing a collection of H. influenzae clinical isolates in our laboratory, we obtained a carbapenem-non-susceptible clinical isolate (NUBL1772) that possessed an altered PBP3 containing V525_N526insM. The aim of this study was to reveal the effect of altered PBP3 containing V525_N526insM on reduced carbapenem susceptibility. After generating recombinant strains with altered ftsI, we performed antimicrobial susceptibility testing and competitive binding assays with fluorescent penicillin (Bocillin FL) and carbapenems. Elevated carbapenem MICs were found for the recombinant strain harboring the entire ftsIgene of NUBL1772. The recombinant PBP3 of NUBL1772 also exhibited reduced binding to carbapenem. These results demonstrate that altered PBP3 containing V525_N526insM influences reduced carbapenem susceptibility. The revertant mutant lacking the V525_N526insM exhibited lower MICs of carbapenem than NUBL1772, suggesting that this insertion affects reduced carbapenem susceptibility. MICs of β-lactam for NUBL1772 was higher than those for the recombinant possessing ftsI of NUBL1772. NUBL1772 harbored AcrR with early termination, resulting in low-level transcription of acrB and high efflux pump activity. These findings suggest that the disruption of AcrR also contributes to the reduced carbapenem susceptibility found in NUBL1772. Our results provide the first evidence that the altered PBP3 containing V525_N526insM is responsible for reduced susceptibility to carbapenem in H. influenzae.

 

FOOTNOTES

#Address correspondence to Kouji Kimura, koujikim@med.nagoya-u.ac.jp

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Haemophilus influenzae.

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