Substantial reduction of antibiotic-non-susceptible pneumococcal otitis media following PCV7/PCV13 sequential introduction

Background: In the pre-pneumococcal conjugated vaccines (PCVs) era, serotypes included in the 7/13-valent PCVs (PCV7/PCV13) caused most pneumococcal otitis media (OM) and antibiotic-non-susceptible pneumococcal OM (ANSP-OM) episodes. In southern Israel, sequential PCV7/PCV13 introduction resulted in 90% reduction of vaccine-serotype OM. Objectives: We assessed the dynamics of ANSP-OM necessitating middle ear fluid culture following PCV7/PCV13 sequential introduction in young children. Methods: This was a prospective, population-based, active surveillance. All episodes in children 3 years old, during 2004-16, were included. Two subperiods were defined: (i) pre-PCV: 2004-08; and (ii) PCV13: 2014-16. ANSP was defined for the following antibiotics: penicillin (MIC0.1 mg/L and1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone, trimethoprim/sulfamethoxazole and chloramphenicol. MDR was defined as ANSP for 3 classes. Results: Overall, 2270 pneumococcal OM episodes were identified. Annual overall pneumococcal, PCV13 and non-PCV13 serotype OM incidence declined by 86%, 97% and 33%, respectively, comparing pre-PCV with the PCV13 period. During 2004-08, 95% of ANSP was observed in vaccine serotypes. Incidence of penicillin (MIC 0.1 mg/L and 1.0 mg/L), macrolide, tetracycline, clindamycin, ceftriaxone and multidrug ANSP-OM declined by 90% in the PCV13 period. Rates of trimethoprim/sulfamethoxazole and chloramphenicol ANSP-OM declined by 85% and 79%, respectively. The proportions of ANSP of all pneumococcal isolates declined by 70% for penicillin, ceftriaxone and erythromycin; 53% for tetracycline; and 55% for MDR, versus no significant reductions observed for chloramphenicol, trimethoprim/sulfamethoxazole and clindamycin. Conclusions: PCV7/PCV13 sequential introduction resulted in rapid and substantial ANSP-OM reduction, in parallel with the near disappearance of PCV13-serotype OM and no increase in replacement disease.