| Summary: | The purpose of this thesis was to molecularly characterize macrolide-resistant S. pneumoniae (SPN) isolates in Canada between 1998 and 2008. The characterization involved looking at the multi-drug resistant phenotype (MDR), the mechanisms of macrolide resistance, the genetic relatedness, the serotype distribution and PCV7 vaccine coverage as well as the determination of presence of pili-virulence factors. The hypothesis of the study was that macrolide-resistant SPN will growingly be MDR, genetically related, piliated and consisting of serotypes not found in PCV7 vaccine.
Over 1500 macrolide-resistant SPN isolates collected between 1998 and 2008 were studied. Macrolide-resistant isolates came from patients from all regions of Canada, and from all age groups. They came from slightly more males (60%) and slightly more in-patients (62%). Macrolide resistant SPN remained low at 8% during the first 4 years of the study, and started to increase reaching 22% by the end of the study in 2008 (p=0.001). Overall the most common mechanism of resistance was efflux mediated by mef(A) (51%), followed by target site modification mediated by erm(B) (36%). The efflux mediated macrolide resistance in S. pneumoniae was predominantly due to the presence of subtype E (95%), which was resistant to more antibiotic classes, and was genetically and serotypically more diverse than the A subtype. Isolates carrying both erm(B) and mef(A) macrolide resistance genes increased overtime from 1% (1998) to 19% (2008) (p=0.002). Serotype distribution showed a decrease in PCV7 vaccine coverage from 67% to 31% (p=0.0072). Isolates with non-PCV7 serotypes increased overtime from 33% to 57% (p=0.0152).
Isolates with serotype 19A increased by 15% (p=0.005). They were found to be multi-drug resistant, carried both erm(B) and mef(A) subtype E macrolide resistance genes, and were genetically related. The presence of virulence factor pili-type 1 (PI-1) and pili-type 2 (PI-2) was found associated with these isolates, possibly contributing to its emergence. In conclusion, macrolide resistant SPN increased during the course of this study mostly due to emergence of multi-drug resistant, genetically related, piliated, 19A S. pneumoniae.
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