Impact of pneumococcal conjugate vaccines introduction on antibiotic resistance of Streptococcus pneumoniae meningitis in children aged 5 years or younger, Israel, 2004 to 2016

Euro Surveill. 2018 Nov;23(47):1800081. doi: 10.2807/1560-7917.ES.2018.23.47.1800081.

Abstract

Background: Empiric treatment of pneumococcal meningitis includes ceftriaxone with vancomycin to overcome ceftriaxone resistant disease. The addition of vancomycin bears a risk of adverse events, including increased antibiotic resistance. We assessed antibiotic resistance rates in pneumococcal meningitis before and after pneumococcal conjugate vaccine (PCV) implementation.

Methods: All pneumococcal meningitis episodes in children aged 5 years and younger, from 2004 to 2016, were extracted from the nationwide bacteremia and meningitis surveillance database. For comparison purposes, we defined pre-PCV period as 2004–2008 and PCV13 period as 2014–2016. Minimal inhibitory concentration (MIC) > 0.06 and > 0.5 μg/mL were defined as penicillin and ceftriaxone resistance, respectively.

Results: Overall, 325 episodes were identified. Pneumococcal meningitis incidence rates declined non-significantly by 17%, comparing PCV13 and pre-PCV periods. Throughout the study, 90% of isolates were tested for antibiotic susceptibility, with 26.6%, 2.1% and 0% of isolates resistant to penicillin, ceftriaxone and vancomycin, respectively. Mean proportions (± SD) of meningitis caused by penicillin-resistant pneumococci were 40.5% ± 8.0% and 9.6% ± 7.4% in the pre-PCV and the PCV13 periods, respectively, resulting in an overall 83.9% reduction (odd ratio:0.161; 95% confidence interval: 0.059–0.441) in penicillin resistance rates. The proportions of meningitis caused by ceftriaxone resistant pneumococci were 5.0% ± 0.8% in the pre-PCV period, but no ceftriaxone resistant isolates were identified since 2010.

Conclusions: PCV7/PCV13 sequential introduction resulted in > 80% reduction of penicillin- resistant pneumococcal meningitis and complete disappearance of ceftriaxone resistant disease. These trends should be considered by the treating physician when choosing an empiric treatment for pneumococcal meningitis.

Keywords: Streptococcus pneumoniae; antibiotic resistance; children; meningitis; pneumococcal conjugate vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Child, Preschool
  • Drug Resistance, Bacterial*
  • Epidemiological Monitoring
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Israel / epidemiology
  • Male
  • Meningitis, Pneumococcal / drug therapy*
  • Meningitis, Pneumococcal / epidemiology
  • Meningitis, Pneumococcal / prevention & control*
  • Microbial Sensitivity Tests
  • Pneumococcal Vaccines / administration & dosage*
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / pharmacology
  • Population Surveillance
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / isolation & purification
  • Vaccines, Conjugate / immunology
  • Vaccines, Conjugate / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Pneumococcal Vaccines
  • Vaccines, Conjugate