Antibiotic resistance, serotypes, and clonal composition of Streptococcus pneumoniae in clinical trials of acute otitis media pre- and post-launch of the 7 valent pneumococcal conjugate vaccine

Abstract number: 1134_01_210

Amrine-Madsen H., Abraham-Van Parijs B., Miller L., Ondus S., Becker J., Jacobs M., Stanhope M.

Objectives:  

Streptococcus pneumoniae is among the most common bacterial pathogens associated with acute otitis media (AOM). Although high levels of efficacy for the 7 valent pneumococcal conjugate vaccine (PCV–7) have been reported for invasive pneumococcal disease, the efficacy with regards to AOM is considerably less clear. Earlier studies involving three prospective, multinational AOM clinical trials, reported on penicillin resistance and serotypes of pre and post PCV-7 S. pneumoniae isolates. The present study expands the analysis of these same samples to include genotyping of all 187 isolates for which penicillin resistance and serotyping data were available.

Methods:  

The genotyping involves our expanded MLST approach, in which all of the customary 7 MLST loci are sequenced not only for the usual 500 bp internal fragment, but for the entire locus, with the addition of several housekeeping loci adjacent to MLST genes. The resulting data set includes approximately 9000 base pairs of sequence data for each isolate, including as a subset, the usual MLST sequence data. These data provide us with high resolution clonal designation of the pre and post PCV-7 samples, while also allowing us to correlate our clonal composition data with the pneumococcal MLST database.

Results:  

In general, the same clones were present in the pre and post PCV-7 samples; however, there tended to be a proportional increase within clones of non-vaccine serotype in the post PCV-7 set (e.g. clones of serotype 11, 29, and 22 increased in proportional representation in post vaccine years). The changes associated with clones of vaccine or vaccine related serotype were more variable, with some clones not changing in proportional abundance (e.g. clones of 19F, 9V and the mixed serotype clone known as Spain 23F-1), others decreasing (e.g. clones of 23F, 14, and 6A), and others increasing (e.g. one 19F clone). One clone of particular interest was represented by 19A isolates pre PCV-7, and in post PCV-7 years was, with the exception of a single serotype 19A isolate, represented entirely by serotype 15B (a serotype not present in the pre PCV-7 set of isolates).

Conclusions:  

Although it is difficult to determine if the introduction of PCV-7 directly caused the changes in the AOM clones documented in this study, our results are consistent with a mixture of clonal expansion of non-vaccine serotypes and occasional serotype switching mediated by the selective pressure of the vaccine.