Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States

Abstract

Streptococcus pneumoniae serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown. The sequence type (ST) composition of 78 serotype 35B isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with otitis media (noninvasive) from 2011 to 2014 was characterized by multilocus sequence typing (MLST). The most common STs were ST558 (69.2%), ST156 (10.3%), and ST452 (3.8%). Two major clonal complexes (CC), CC558 and CC156, were identified by eBURST analysis. Overall, 91% (71/78) of isolates were penicillin nonsusceptible and 16.7% (13/78) were MDR. Among all invasive serotype 35B isolates, MDR isolates increased significantly, from 2.9% (1/35) to 27.9% (12/43) (P ϭ 0.004), after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced. All CC156 isolates were identified after the introduction of PCV13 (0/35 [0%] before versus 9/43 [20.9%] after; P ϭ 0.003) and were MDR. All CC156 isolates had similar antimicrobial susceptibility patterns; in contrast, high variability in antimicrobial susceptibility was observed among CC558 isolates. The distributions of CC558 and CC156 among invasive and noninvasive isolates were not different. The increased prevalence of MDR serotype 35B after the introduction of PCV13 was directly associated with the emergence of ST156. Genotyping suggests that capsular switching has occurred between MDR vaccine serotypes belonging to ST156 (e.g., 9V, 14, and 19A) and serotype 35B.

The impact of the ancillary pilus‐1 protein RrgA of Streptococcus pneumoniae on colonization and disease

“…One of the major pilus‐1 carrying lineages, ST4414, comprises a single clone of 19A isolates from the Maela collection (Chewapreecha et al, ), and interestingly this clone also carries a mega element encoding macrolide resistance (Croucher et al, ). The pilus‐1 positive lineages ST558 (serotype 35B) and ST156 (9V, 35B, 9A and19A) have been associated with decreased susceptibility to penicillin (Olarte et al, ; Sjöström et al, ) , and ST802 and ST4413 are single locus variants and are of serotype 23A. Interestingly, the only exceptional lineage where only 15% of the strains carry the pilus‐1 islet is ST199 (15B/C, 19A).…”

The Ongoing Genetic Adaptation of Streptococcus pneumoniae

“…The susceptibility profiles and genetic composition of invasive and noninvasive serotype 35B isolates were similar (19).…”

“…In this issue of the Journal of Clinical Microbiology, Olarte and colleagues provide new information regarding genetic events that have contributed to the increasing (19). The susceptibility profiles and genetic composition of invasive and noninvasive serotype 35B isolates were similar (19).…”

“…The ability of this antimicrobialresistant strain to acquire a serotype not recognized by the 13-valent conjugate vaccine illustrates a basic biologic principle: bacteria have ways of escaping mammalian host responses. Although Olarte et al found that serotype 35B strains caused the majority of cases of invasive pneumococcal disease in their surveillance program, only 8 isolates were ST156 (19).…”

WciG O -Acetyltransferase Functionality Differentiates Pneumococcal Serotypes 35C and 42

“…Widespread vaccination has removed the vaccine-targeted serotypes from both asymptomatic carriage (6) and IPD (7), but clearance of these serotypes from nasopharyngeal carriage has increased the relative prevalence of rarer serotypes such as serotype 35B (8,9). Thus, serotypes that are currently rare may become more widespread after implementation of subsequent generations of conjugate vaccines.…”