Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

Abstract

Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.

FIG 1

Approximate numbers of cases per 100,000 individuals caused by penicillin resistance for each year (left). These data encompass all clonal complexes and serotypes associated with penicillin resistance (MIC of ≥2 μg/ml) in cases of pediatric IPD during 1999, 2009, and 2013. The circle diameters reflect relative IPD incidences.

FIG 2

ABCs IPD rates in the population of individuals <5 years of age in 1999 (before PCV7 introduction), 2009 (9 years after PCV7 introduction), and 2013 (3 years after PCV13 introduction). The bright red portions indicate penicillin resistance (MICs of ≥2 μg/ml), lighter red indicates intermediate resistance (0.12 to 1.0 μg/ml), and gray indicates sensitivity (≤0.06 μg/ml). PCV13 types, besides those targeted by PCV7, are indicated in red and purple. Only nonvaccine types (NVT) that are found associated with intermediate or high penicillin resistance are specifically indicated in black boldface type.

FIG 3

Incidences (number of cases per 100,000 individuals) of antimicrobial-nonsusceptible (nonsusceptible to one or more classes of antimicrobials, including macrolides, cephalosporins, tetracyclines, penicillins, fluoroquinolones, and glycopeptides) IPD. (Data from Active Bacterial Core surveillance, 2009 to 2013.)