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

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.

Figure 1

Pneumococcal meningitis incidence rates in children aged 5 years and younger, Israel, July 2000–June 2016 (n = 455)

Figure 2

Proportions of penicillin-resistant pneumococcal meningitis of all isolates in children aged 5 years or younger, Israel, July 2004–June 2016 (n = 289)

Figure 3

Proportions of ceftriaxone-resistant pneumococcal meningitis of all isolates in children aged 5 years and younger, Israel, July 2004–June 2016 (n = 291)

Figure 4

Proportions of PCV13 serotypes of all penicillin-resistant pneumococcal meningitis isolates in in children aged 5 years or younger, Israel, July 2004–June 2016 (n = 325)