Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004–2016

Lotta Siira,Didrik F Vestrheim,Brita A Winje,Dominique A Caugant,Anneke Steens

doi:10.1016/j.vaccine.2020.06.040

Abstract

Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004–2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0–102 years old; median 64 years. Carriage study participants were typically aged 1–5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006–2010). In the PCV13 period (2011–2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR.

Highlights

Streptococcus pneumoniae, the pneumococcus, can cause mild infections, like otitis media, or severe invasive pneumococcal disease (IPD)
Overall 10,239 IPD cases were available for this study; for 92% both, serotype and antimicrobial susceptibility data was available from the isolate (n = 9438; supplementary Table 1)
Our study covering 13 years of antimicrobial susceptibility surveillance in whole Norway showed that antimicrobial resistance (AMR) is low, but the incidence changed following changes in pneumococcal childhood vaccination

Summary

Introduction

Streptococcus pneumoniae, the pneumococcus, can cause mild infections, like otitis media, or severe invasive pneumococcal disease (IPD). In addition to preventing IPD, PCVs decrease carriage of vaccine serotypes and affect transmission in the population [4,5]. The 7-valent PCV (PCV7), covering serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was included in the childhood immunisation programme in Norway in July 2006. It was replaced by the 13-valent vaccine (PCV13) covering six additional serotypes (1, 5, 3, 6A, 7F, 19A) in April 2011. Childhood PCV use resulted in a decline in the incidence of IPD caused by vaccine-serotypes as well as overall IPD, especially in the youngest and oldest age groups due to direct and indirect protection, respectively [6,7,8]

Objectives

Methods

Results

Conclusion