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.