Naim Ouldali1,2,3,4, Robert Cohen1,2,5,6,7,8, Corinne Levy1,2,5,6,7, Nathalie Gelbert-Baudino2,5, Elisa Seror1,9, François Corrard1,5, François Vie Le Sage2,5, Anne-Sylvestre Michot1, Olivier Romain1,2,10, Stéphane Bechet1,2,6, Stéphane Bonacorsi11,12, François Angoulvant2,4,13, Emmanuelle Varon14. 1. ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Saint Maur-des-Fossés, France. 2. GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France. 3. Unité d'épidémiologie clinique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, ECEVE INSERM UMR 1123, Paris, France. 4. Urgences pédiatriques, hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France. 5. AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France. 6. Université Paris Est, IMRB-GRC GEMINI, Créteil, France. 7. Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, Créteil, France. 8. Unité Court Séjour, Petits nourrissons, Service de Néonatalogie, Centre Hospitalier Intercommunal de Créteil, France. 9. Hématologie pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France. 10. Réanimation et pédiatrie néonatales, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, Clamart, France. 11. Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 12. Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France. 13. Centre de recherche des Cordeliers, INSERM UMR 1138, Paris, France. 14. National Reference Center for Pneumococci, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
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.
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.
Authors: Alexis Rybak; Corinne Levy; François Angoulvant; Anne Auvrignon; Piotr Gembara; Kostas Danis; Sophie Vaux; Daniel Levy-Bruhl; Sylvie van der Werf; Stéphane Béchet; Stéphane Bonacorsi; Zein Assad; Andréa Lazzati; Morgane Michel; Florentia Kaguelidou; Albert Faye; Robert Cohen; Emmanuelle Varon; Naïm Ouldali Journal: JAMA Netw Open Date: 2022-06-01
Authors: Stephanie W Lo; Kate Mellor; Robert Cohen; Alba Redin Alonso; Sophie Belman; Narender Kumar; Paulina A Hawkins; Rebecca A Gladstone; Anne von Gottberg; Balaji Veeraraghavan; K L Ravikumar; Rama Kandasamy; Sir Andrew J Pollard; Samir K Saha; Godfrey Bigogo; Martin Antonio; Brenda Kwambana-Adams; Shaper Mirza; Sadia Shakoor; Imran Nisar; Jennifer E Cornick; Deborah Lehmann; Rebecca L Ford; Betuel Sigauque; Paul Turner; Jennifer Moïsi; Stephen K Obaro; Ron Dagan; Idrissa Diawara; Anna Skoczyńska; Hui Wang; Philip E Carter; Keith P Klugman; Gail Rodgers; Robert F Breiman; Lesley McGee; Stephen D Bentley; Carmen Muñoz-Almagro; Emmanuelle Varon Journal: Lancet Microbe Date: 2022-08-16