Evolution of Penicillin Non-susceptibility Among Streptococcus pneumoniae Isolates Recovered From Asymptomatic Carriage and Invasive Disease Over 25 years in Brazil, 1990–2014

Streptococcus pneumoniae is a major cause of community-acquired pneumonia and meningitis, and it is also found as a commensal, colonizing the human upper respiratory tract of a portion of the human population. Its polysaccharide capsule allows the recognition of more than 90 capsular types and represents the target of the currently available pneumococcal conjugate vaccines (PCVs), such as the 10-valent (PCV10) and the 13-valent (PCV13). Penicillin non-susceptible pneumococci (PNSP) have been listed as one of the current major antimicrobial-resistant pathogen threats. In Brazil, the emergence of PNSP was initially detected in the mid 1990s and PCV10 has been part of the National Immunization Program since 2010. Here, we investigated the distribution of capsular types and penicillin susceptibility profiles of 783 pneumococcal strains isolated in Brazil between 1990 and 2014 to assess the evolution of penicillin non-susceptibility among pneumococci associated with asymptomatic carriage and invasive pneumococcal disease (IPD). The most common serotypes among carriage isolates were 19F, 6B, 6C, 23F, and 14. Among IPD isolates, the most frequent types were 14, 3, 6B, 5, 19F, and 4. We detected 21 types exclusively associated with IPD isolates, whereas non-typeable (NT) isolates were only detected in carriage. Nearly half of the isolates belonged to PCV10 serotypes, which remarkably decreased in occurrence (by nearly 50%) after PCV10 introduction (2011–2014), while non-PCV10 serotypes increased. PNSP frequency and levels were much higher among carriage isolates, but PNSP belonging to PCV10 serotypes were more common in IPD. While the occurrence of PNSP has decreased significantly among IPD isolates since 2011, it kept increasing among carriage strains. Such a difference can be attributed to the serotypes that emerged in each clinical source after PCV10 usage. PNSP with multidrug resistance profiles that emerged within carriage isolates comprised mostly serotypes 6C and 35B, as well as NT isolates. In turn, penicillin-susceptible capsular types 3, 20, and 8 have risen among IPD. Overall, our results reinforce the relevance of PNSP surveillance over a long period of time to better understand the dynamics of antimicrobial resistance in response to PCV introduction and may also contribute to improve control measures toward drug-resistant pneumococci.