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Published on: February 23, 2014
Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States
Liset Olarte1, Sheldon L Kaplan2, William J Barson3
1Department of Pediatrics of Baylor College of Medicine, Houston, Texas, USA liset.olarte@alumni.bcm.edu khulten@bcm.edu.
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 = 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 = 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.
Insights
Multidrug-resistant Streptococcus pneumoniae serotype 35B has increased significantly following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). This rise is linked to the emergence of sequence type 156 (ST156), suggesting capsular switching events.
Area of Science:
- Microbiology
- Genetics
- Epidemiology
Background:
- Streptococcus pneumoniae serotype 35B is a nonvaccine serotype known for high penicillin nonsusceptibility.
- Recent reports indicate an increasing proportion of multidrug-resistant (MDR) 35B isolates, with unknown underlying genetic factors.
Purpose of the Study:
- To characterize the sequence type (ST) composition of serotype 35B isolates.
- To investigate the genetic events contributing to the emergence of multidrug-resistant (MDR) serotype 35B.
- To determine the association between the 13-valent pneumococcal conjugate vaccine (PCV13) introduction and the rise of MDR 35B.
Main Methods:
- Multilocus sequence typing (MLST) was used to analyze 78 invasive and 48 noninvasive serotype 35B isolates collected between 1994 and 2014.
- eBURST analysis was employed to identify clonal complexes (CCs).
- Antimicrobial susceptibility patterns were assessed for different sequence types and clonal complexes.
Main Results:
- The most prevalent sequence types (STs) were ST558 (69.2%) and ST156 (10.3%), forming two major clonal complexes (CC558 and CC156).
- Overall, 91% of isolates were penicillin nonsusceptible, and 16.7% were MDR.
- MDR invasive serotype 35B isolates significantly increased from 2.9% before PCV13 to 27.9% after PCV13 introduction (P = 0.004).
- All CC156 isolates, identified post-PCV13, were MDR (20.9% of isolates after PCV13), unlike CC558 isolates which showed varied susceptibility.
- The emergence of ST156 was directly associated with the increased prevalence of MDR serotype 35B post-PCV13, with evidence of capsular switching from other MDR vaccine serotypes.
Conclusions:
- The increased prevalence of multidrug-resistant (MDR) serotype 35B following PCV13 introduction is strongly linked to the emergence and spread of ST156.
- Capsular switching events involving ST156 are likely contributing to the rise of MDR nonvaccine serotypes.
- These findings highlight the need for ongoing surveillance of nonvaccine serotypes and their resistance patterns.
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