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.


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
01 10 2019
Historique:
received: 27 03 2019
revised: 21 05 2019
accepted: 03 06 2019
pubmed: 8 7 2019
medline: 21 8 2020
entrez: 8 7 2019
Statut: ppublish

Résumé

Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 31280295
pii: 5529307
doi: 10.1093/jac/dkz281
doi:

Substances chimiques

Anti-Bacterial Agents 0
Pneumococcal Vaccines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3077-3086

Informations de copyright

© 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.

Auteurs

Naim Ouldali (N)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
Unité d'épidémiologie clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, ECEVE INSERM UMR 1123, Paris, France.
Urgences pédiatriques, hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France.

Robert Cohen (R)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France.
Université Paris Est, IMRB-GRC GEMINI, Créteil, France.
Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, Créteil, France.
Unité Court Séjour, Petits nourrissons, Service de Néonatalogie, Centre Hospitalier Intercommunal de Créteil, France.

Corinne Levy (C)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France.
Université Paris Est, IMRB-GRC GEMINI, Créteil, France.
Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, Créteil, France.

Nathalie Gelbert-Baudino (N)

GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France.

Elisa Seror (E)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
Hématologie pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France.

François Corrard (F)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France.

François Vie Le Sage (F)

GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France.

Anne-Sylvestre Michot (AS)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.

Olivier Romain (O)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
Réanimation et pédiatrie néonatales, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, Clamart, France.

Stéphane Bechet (S)

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France.
GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
Université Paris Est, IMRB-GRC GEMINI, Créteil, France.

Stéphane Bonacorsi (S)

Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France.

François Angoulvant (F)

GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.
Urgences pédiatriques, hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France.
Centre de recherche des Cordeliers, INSERM UMR 1138, Paris, France.

Emmanuelle Varon (E)

National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil, Créteil, France.

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Classifications MeSH