Bacterial resistance to commonly used antimicrobial
agents has increased exponentially in the last decade.
Therapeutic choices to treat once predictably susceptible
bacteria have become increasingly limited due to the
spread of resistant organisms, both in community and
hospital settings. In some areas of North America, the
prevalence of certain multi-drug resistant organisms
such as Staphylococcus aureus, Enterococcus spp.,
and Streptococcus pneumoniae has reached endemic
My laboratory is currently engaged in several research
endeavors related to both the molecular epidemiology
of antimicrobial resistance and the molecular mechanisms
of antimicrobial resistance.
Surveillance of antimicrobial resistance in respiratory
tract pathogens: Accurate and current data on regional
antimicrobial resistance trends are crucial for the
clinician to best select appropriate empiric antimicrobial
therapy for his/her patients. In Canada and the United
States, the prevalence of penicillin and multi-drug
resistant S.pneumoniae and beta-lactamase producing Haemophilus
influenzae has dramatically increased over the
last decade resulting in changes to empiric antimicrobial
management. To this end, our laboratory actively participates
in the collection and susceptibility testing of the
major bacterial respiratory tract pathogens, (S.pneumoniae, H.influenzae,
and Moraxella catarrhalis), in both the province
of Nova Scotia and across Canada.
Molecular epidemiology of fluoroquinolone and macrolide
resistance in S.pneumoniae and S.pyogenes (group
Historically, the fluoroquinolones have not been used
to treat pneumococcal infections, however, a new generation
of these agents with potent anti-pneumococcal activity
has recently been approved for clinical use. Our laboratory
concentrates on studying the molecular basis of fluoroquinolone
resistance in S.pneumoniae. Resistance to these
agents is known to arise through mutations in the genes
coding for Topoisomerase IV (parC/parE), and DNA
gyrase (gyrA/gyrB), and through the action of
an energy dependent efflux system (pmrA gene).
Until recently, it was thought that these mutations arose
spontaneously and were selected for by antibiotic pressure.
Recent evidence suggests that S.pneumoniae may
also acquire DNA from fluoroquinolone resistant viridans
and oral streptococci and produce "mosaic" topoisomerase
enzymes through recombination. We are currently trying
to understand which mutations give rise to high level
fluoroquinolone resistance and what role the efflux system
plays in the development of resistance.
The macrolides, (erythromycin, clarithromycin, and
azithromycin), are oral antibiotics commonly used to
treat respiratory tract disease. Resistance to these
agents can arise through target site modification (acquisition
of the erm genes), or through energy dependent
efflux (mef gene). Our laboratory concentrates
in understanding the molecular epidemiology of macrolide
resistance in S.pneumoniae and S.pyogenes.