OVERVIEW:

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 proportions.

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 A Streptococcus):

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.