Impact of the heptavalent Pneumococcal Conjugate Vaccine (PCV7) on the molecular determinants of macrolide resistance among invasive isolates of Streptococcus pneumoniae in the United States Public

Hawkins, Paulina (2011)

Permanent URL: https://etd.library.emory.edu/concern/etds/ns064673h?locale=fr
Published

Abstract

Background: Pneumococcal macrolide resistance is usually expressed as one of two phenotypes:
the M phenotype, mediated by the mefA/E gene, or the MLS(B) phenotype, mediated by the ermB
gene. The predominant mechanism of resistance in the U.S. was until recently mediated by the
mefA gene, but its prevalence has decreased since the introduction of the heptavalent
pneumococcal vaccine (PCV7) in 2000. The main purpose of this study was to determine whether
the ermB + mefA genotype has become the most prevalent mechanism instead. Methods: We
determined serotype, phenotype and genotype for 4535 erythromycin-resistant isolates submitted
to the ABCs program from participating sites pre (1999) and post (2002-2007) introduction of
PCV7. Logistic regression models were fitted to determine risk factors associated with the MLS(B)
phenotype among these isolates. Results: The five most common serotypes associated with
macrolide resistance were 19A, 14, 6A, and 15A; the prevalence of 14 and 6A was greatly
reduced by PCV7, but 19A and 15A (non-PCV7 serotypes) have increased significantly since
1999, along with macrolide resistance. The dual ermB + mefA/E genotype increased significantly
among these isolates, while the mefA/E only genotype went from being the most predominant
mechanism of erythromycin resistance in the U.S. in 1999 (80.2%) to accounting for only half of
the resistant isolates in 2007. These changes were closely related to changes in serotype
distribution. Isolates with a non-PCV7 serotype (especially 19A), that were collected in
California, or that possessed multidrug resistance, were more likely to have an MLS(B) phenotype.
Fifteen isolates were found to have alternative resistance mechanisms (mutations in L4 riboprotein
or presence of ermA (ermTR)). Conclusions: The mefA/E genotype, which was the predominant
mechanism of erythromycin resistance among U.S. IPD isolates before the introduction of PCV7,
is quickly being replaced by the dual ermB + mefA/E genotype, mostly due to increases in
serotype 19A. Since the new 13-valent pneumococcal vaccine (PCV13) contains 19A, this trend
will possibly be reversed in the next few years. Most significantly, alternative mechanisms that
have rarely been reported were found among these isolates, including several previously
unpublished mutations in the L4 ribosomal protein.

Table of Contents

TABLE OF CONTENTS

BACKGROUND ....................................................................................................................................1


METHODS ............................................................................................................................................6
Surveillance........................................................................................................................................6

Serotyping and antimicrobial susceptibility testing....................................................................................6
DNA extraction....................................................................................................................................7

Polymerase Chain Reaction (PCR) amplification and Sequencing.................................................................7
Statistical Analyses..............................................................................................................................8

RESULTS...............................................................................................................................................9
Isolates..............................................................................................................................................9

Invasive serotypes...............................................................................................................................9
Mechanisms of erythromycin resistance................................................................................................ 10
Factors associated with MLS(B) phenotype............................................................................................ 13

DISCUSSION ...................................................................................................................................... 14


TABLES AND FIGURES........................................................................................................................... 18
Table 1 ............................................................................................................................................ 18
Table 2. ........................................................................................................................................... 19
Table 3 ............................................................................................................................................ 20
Table 4 ............................................................................................................................................ 20
Table 5 ............................................................................................................................................ 21
Table 6 ............................................................................................................................................ 22
Figure 1............................................................................................................................................ 23
Figure 2............................................................................................................................................ 24
Figure 3............................................................................................................................................ 25

REFERENCES.................................................................................................................................... 26


APPENDIX ........................................................................................................................................ 32

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