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UBC Theses and Dissertations

Antimicrobial resistance in invasive pneumococcal disease Winters, Meghan Lesley


Antimicrobial resistance in Streptococcus pneumoniae has increased in recent decades at a frightening pace. The infant conjugate vaccine program, introduced in BC in 2003, is a tool for the control of invasive pneumococcal disease (IPD) with substantial potential to combat antimicrobial resistance. The first phase of this thesis linked surveillance programs at the BC Centre for Disease Control and the National Centre for Streptococcus to evaluate recent trends in IPD incidence, serotype distribution, and antimicrobial resistance. Based on 1,288 reported cases of IPD over 2002-2005, there was a significant decrease in the incidence in children <5 years. Over half of reported cases (728/1,288) were referred for serotype and susceptibility testing. Of these, the proportion that were of vaccine-preventable serotypes declined from 68.9% to 43.8% between 2002 and 2005; in children <2 years, the decline was from 83.0% to 16.7%. The prevalence of isolates with reduced susceptibility was highest for trimethoprim-sulfamethazole (15.3% non-susceptible, 111/725 tested), penicillin (9.I%, 66/728), and erythromycin (9.l%, 661727), and to [greater than or equal to]2 classes of antimicrobials (10.3%, 75/728). Arguably, the most important driver of resistance is antimicrobial use. With access to BC’s rich province-wide prescription database, we were able to conduct a retrospective cohort study to investigate the risk posed by an individual’s prior antimicrobial consumption patterns. We obtained historical records from PharmaNet for all IPD cases reported from 2001 to February 2005 that had complete antimicrobial susceptibility testing (n=564). In multivariable modeling, use of trimethoprim-sulfamethoxazole was significantly associated with having a penicillin non-susceptible infection (OR=2.92, 95% CI:1.34-6.38). Penicillins (OR=2.12, 95% CI:1.13-3.98) or macrolides/lincosamides (OR=2.00,95% CI:1.09- 3.68) were independently associated with erythromycin non-susceptible infections, and trimethoprim-sulfamethoxazole with trimethoprimsulfamethoxazole non-susceptibility (OR=2.09, 95% CI:1.01-4.31). Of the macrolides, only azithromycin consumption posed a significant risk for erythromycin resistance, with an etiologic fraction of over two-thirds. The transfer of these findings into the policy realm provides timely evidence on epidemiological trends in IPD in the era of the conjugate vaccine, and informs on the risk posed by certain commonly prescribed antimicrobials. Class-specific risk measures can be used to direct targeted prescription policy action for the control of antimicrobial resistance.

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