Dynamics of Antibiotic Resistance of Streptococcus pneumoniae in France: A Pediatric Prospective Nasopharyngeal Carriage Study from 2001 to 2022

Abstract

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for <1%, and non-PCV15/PCV20 accounted for 28%. The next generation PCVs, particularly PCV20, may disrupt nasopharyngeal carriage and contribute to decreasing the rate of antibiotic resistance among pneumococci.

Keywords: PCV impact; acute otitis media; children; next-generation pneumococcal conjugate vaccine; pneumococcal nasopharyngeal carriage; third-generation pneumococcal conjugate vaccine.

Figure 1

Evolution of overall Streptococcus pneumoniae (Sp) carriage in children with acute otitis media enrolled during the study period (n = 17,136). Notes: The black lines show the observed data. Using a segmented regression model, we estimated the rates over time (blue slope lines) and its 95% confidence interval (blue dotted lines). The “pre-PCV7 period” was from September 2001 to December 2002, the “targeted PCV7 period” from January 2003 to May 2006, the “PCV7 period” from June 2006 to May 2010, the “early PCV13 period” from June 2010 to April 2014 and the “late PCV13 period” from May 2014 to July 2022.

Figure 2

Evolution of penicillin and erythromycin non-susceptibility among the pneumococcal strains isolated from nasopharyngeal carriage. Notes: The black lines show the observed data. Using a segmented regression model, we estimated the rates over time (blue slope lines) and its 95% confidence interval (blue dotted lines). The “pre-PCV7 period” was from September 2001 to December 2002, the “targeted PCV7 period” from January 2003 to May 2006, the “PCV7 period” from June 2006 to May 2010, the “early PCV13 period” from June 2010 to April 2014 and the “late PCV13 period” from May 2014 to July 2022.

Figure 3

(a,b). Serotype distribution during the pre-PCV7, PCV7, early PCV13 and late PCV13 periods. The “pre-PCV7 period” was from September 2001 to December 2002, the “PCV7 period” from June 2006 to May 2010, the “early PCV13 period” from June 2010 to April 2014 and the “late PCV13 period” from May 2014 to July 2022. Note: Serotypes accounting for <1% in both periods are not shown. PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; NT, non-typable.

Figure 4

Serotype distribution among penicillin non-susceptible Sp strains isolated during the pre-PCV7, PCV7, early PCV13 and late PCV13 periods. Notes: The “pre-PCV7 period” was from September 2001 to December 2002, the “PCV7 period” from June 2006 to May 2010, the “early PCV13 period” from June 2010 to April 2014 and the “late PCV13 period” from May 2014 to July 2022. The “early PCV13 period” was from June 2010 to April 2014 and the “late PCV13 period” from May 2014 to July 2022. Serotypes isolated in <1.0% of patients during each period are not shown.