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Background. Streptococcus pneumoniae can cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by a S. pneumoniae strain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to this S. pneumoniae strain and to characterize the outbreak in British Columbia using whole-genome sequencing. Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands. Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasive S. pneumoniae isolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain. Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome.

BACKGROUND: Drug resistance indexes (DRIs) quantify the cumulative impact of antimicrobial resistance on the likelihood that a given pathogen will be susceptible to antimicrobial therapy.OBJECTIVE: To derive a DRI for community urinary tract infections caused by Escherichia coli in British Columbia for the years 2007 to 2010, and to examine trends over time and across patient characteristics.METHODS: Indication-specific utilization data were obtained from BC PharmaNet for outpatient antimicrobial prescriptions linked to diagnostic information from physician payment files. Resistance data for E coli urinary isolates were obtained from BC Biomedical Laboratories (now part of LifeLabs Medical Laboratory Services). DRIs were derived by multiplying the rate of resistance to a specific antimicrobial by the proportional rate of utilization for that drug class and aggregating across drug classes. Higher index values indicate more resistance.RESULTS: Adaptive-use DRIs remained stable over time at approximately 18% (95% CI 17% to 18%) among adults ≥15 years of age and approximately 28% (95% CI 26% to 31%) among children <15 years of age. Similar results were observed when proportional drug use was restricted to the baseline year (ie, a static-use model). Trends according to age group suggest a U-shaped distribution, with the highest DRIs occurring among children <10 years of age and adults ≥65 years of age. Males had consistently higher DRIs than females for all age groups.CONCLUSIONS: The stable trend in adaptive-use DRIs over time suggests that clinicians are adapting their prescribing practices for urinary tract infections to local resistance patterns. Results according to age group reveal a higher probability of resistance to initial therapy among young children and elderly individuals.

INTRODUCTION: β-lactam antimicrobials are the most commonly prescribed group of antimicrobials in Canada, and are categorized by the WHO as critically and highly important antimicrobials for human medicine. Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is highly important.OBJECTIVE: To assess the use of penicillin and cephalosporin antimicrobials within Canadian provinces over the 1995 to 2010 time frame according to two metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses dispensed per prescription.METHODS: Antimicrobial prescribing data were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and population data were obtained from Statistics Canada. The two measures developed were used to produce linear mixed models to assess differences among provinces and over time for the broad-spectrum penicillin and cephalosporin groups, while accounting for repeated measurements at the provincial level.RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. A >28% reduction in broad-spectrum penicillin prescribing occurred in each province from 1995 to 2010, and a >18% reduction in cephalosporin prescribing occurred in all provinces from 1995 to 2010, with the exception of Manitoba, where cephalosporin prescribing increased by 18%.DISCUSSION: Significant reductions in the use of these important drugs were observed across Canada from 1995 to 2010. Newfoundland and Labrador and Quebec emerged as divergent from the remaining provinces, with high and low use, respectively.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is very important.OBJECTIVE: To assess the use of macrolide and lincosamide (ML) antimicrobials within Canadian provinces over time, and to compare use rates with those reported by European countries.METHODS: Antimicrobial prescribing data were used to develop two yearly metrics: prescriptions per 1000 inhabitant-days (PrIDs) and the mean defined daily doses (DDDs) per prescription, which were then used to build linear mixed models to assess differences among provinces over time.RESULTS: After accounting for repeated measures over time, prescribing rates (PrIDs) varied significantly according to province and year (P<0.001). However, little change occurred within each province over the time frame studied; from 1995 to 2010, each province had a PrID change <0.01. Quebec and British Columbia had significantly lower prescribing rates than all other provinces. No overall secular trend was apparent. In contrast, the DDDs per prescription did not vary significantly according to province, but showed a significant year-to-year increase.DISCUSSION: ML prescribing varied among provinces in Canada between 1995 and 2010, but remained relatively stable within each province. The average DDDs per ML prescription did not vary according to province, but increased linearly over time. These increases are likely to indicate that fewer prescriptions are being written for children over time, a practice supported by good antimicrobial stewardship principles.

BACKGROUND: The volume and patterns of antimicrobial drug use are key variables to consider when developing guidelines for prescribing, and programs to address stewardship and combat the increasing prevalence of antimicrobial resistant pathogens. Because drug programs are regulated at the provincial level, there is an expectation that antibiotic use may vary among provinces.OBJECTIVE: To assess these potential differences according to province and time.METHODS: Provincial antimicrobial prescribing data at the individual drug level were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance for 2000 to 2010. Data were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the average defined daily doses per prescription. The proportion of liquid oral prescriptions of total prescriptions was also calculated as a proxy measure for the proportion of prescriptions given to children versus adults. To assess the significance of provincial antimicrobial use, linear mixed models were developed for each metric, accounting for repeated measurements over time.RESULTS: Significant differences among provinces were found, as well as significant changes in use over time. Newfoundland and Labrador was found to have significantly higher prescribing rates than all other provinces (P<0.001) in 2010, as well as the mean of all other provinces (P<0.001). In contrast, Quebec exhibited significantly lower prescribing than all other provinces (P<0.001 for all provinces except British Columbia, where P=0.024) and the mean of all other provinces (P<0.001).DISCUSSION/CONCLUSION: Reports of reductions in antimicrobial use at the Canadian level are promising, especially prescribing to children; however, care must be taken to avoid the pitfall of the ecological fallacy. Reductions are not consistent among the provinces or among the classes of antimicrobial drugs dispensed in Canada.

INTRODUCTION: Monitoring the volume and patterns of use of antimicrobial agents is important in light of antimicrobial resistance.OBJECTIVE: To assess the use of three antimicrobial groups – tetracycline, sulfonamide-trimethoprim and ‘other’ antimicrobials – within Canadian provinces over time.METHODS: Prescription counts from 1995 to 2010 were acquired for the tetracycline and sulfonamide-trimethoprim groups of antimicrobials, and from 2001 to 2010 for the ‘other’ antimicrobial group. Linear mixed models were produced to assess differences among provinces and over time while accounting for repeated measurements. Prescription rate, defined daily dose per 1000 inhabitant-days and defined daily doses per prescription measures for the year 2009 were also compared with those reported by participating European Union countries to determine where Canadian provinces rank in terms of antimicrobial use among these countries.RESULTS: Prescribing of all three groups varied according to province and over time. Tetracycline and sulfonamide-trimethoprim group prescribing were significantly reduced over the study period, by 36% and 61%, respectively. Prescribing of the ‘other’ antimicrobial group increased in all provinces from 2001 to 2010 with the exception of Prince Edward Island, although by varying amounts (10% to 61% increases).DISCUSSION: The overall use of antimicrobials in Canada has dropped from 1995 to 2010, and the tetracycline and sulfonamide-trimethoprim groups have contributed to this decline. The use of the ‘other’ antimicrobials has increased, however. These results may suggest that switches are being made among these groups, particularly among the antimicrobials used to treat urinary tract infections.

OBJECTIVES:To determine whether utilization of moxifloxacin, a broad-spectrum fluoroquinolone antibiotic, has changed since its addition to the British Columbia provincial formulary in 2009 and to determine whether utilization was guideline concordant.METHODS: BC PharmaNet prescriptions for moxifloxacin from 2001 to 2010 were anonymously linked to associated Medical Services Plan fee-for-service practitioner claims for indication-specific analysis. Prescribing trends for adults ≥18 years of age were described using defined daily dose (DDD) per 1000 person-years. Monthly utilization rates were fit to a linear regression model that controlled for seasonal variation to examine the effect of the formulary addition.RESULTS: Utilization rose more than sevenfold throughout the study period, from 21.3 DDD per 1000 person-years in 2001 to 163.3 DDD per 1000 person-years in 2010. Although the formulary addition was not associated with an immediate increase in utilization (7.5% [95% CI −4.4% to 20.9%]; P=0.226), it was associated with an overall increase in utilization of 2.1% (95% CI 1.3% to 3.0%; P<0.001) for every month after 2009. Overall, only 29% of moxifloxacin prescriptions could be linked to a diagnostic code that was considered to be guideline concordant. In more than one-half of moxifloxacin prescriptions, the patient had not used another antibiotic in the previous 90 days. Among moxifloxacin prescriptions in which another antibiotic had been used in the previous 90 days, 41.5% were prescriptions for an alternative fluoroquinolone.CONCLUSIONS: The formulary addition was associated with a sustained increase in moxifloxacin utilization over time. Moxifloxacin is often prescribed to patients for indications that are not guideline concordant or to patients who have not previously received first-line antibiotics.

INTRODUCTION: Because antimicrobial use is commonly associated with the development of antimicrobial resistance, monitoring the volume and patterns of use of these agents is important.OBJECTIVE: To assess the use of quinolone antimicrobials within Canadian provinces over time.METHODS: Antimicrobial prescribing data collected by IMS Health Canada were acquired from the Canadian Integrated Program for Antimicrobial Resistance Surveillance and the Canadian Committee for Antimicrobial Resistance, and were used to calculate two yearly metrics: prescriptions per 1000 inhabitant-days and the mean defined daily doses (DDDs) per prescription. These measures were used to produce linear mixed models to assess differences among provinces and over time, while accounting for repeated measurements.RESULTS: The quinolone class of antimicrobials is used similarly among Canadian provinces. Year-to-year increases in quinolone prescribing occurred from 1995 to 2010, with a levelling off in the latter years. Year-to-year decreases in the DDDs per prescription were found to be significant from 2000 to 2010.DISCUSSION: Although the overall use of antimicrobials differs significantly among Canadian provinces, the use of the quinolone class does not vary at the provincial level. Results suggest that prescribing of ciprofloxacin may be a potential target for antimicrobial stewardship programs; however, decreases in the average DDDs per prescription suggest continued uptake of appropriate treatment guidelines.

OBJECTIVE: Antibiotic resistance is accelerated by the overuse of antibiotics. Do Bugs Need Drugs? is an educational program adapted in British Columbia to target both the public and health care professionals, with the aim of reducing unnecessary prescribing. The current article presents a descriptive evaluation of the impact of the program over the first four years.METHOD: Program implementation was measured by the amount of educational material distributed and the level of participation in educational sessions. The impact of the program was assessed by measuring changes in knowledge and prescribing habits of participating physicians, and by investigating provincial trends in antibiotic use.METHOD: Program implementation was measured by the amount of educational material distributed and the level of participation in educational sessions. The impact of the program was assessed by measuring changes in knowledge and prescribing habits of participating physicians, and by investigating provincial trends in antibiotic use.RESULTS: A total of 51,367 children, assisted-living residents and health care professionals have participated in the program since its inception in the fall of 2005. Pre- and postcourse assessments of participating physicians indicated significant improvements in clinical knowledge and appropriate antibiotic treatment of upper respiratory tract infections. Overall rates of antibiotic use in the province have stabilized since 2006. The rates of consumption of fluoroquinolones and macrolides have levelled off since 2005. Utilization rates for acute bronchitis are at the same level as when the program was first implemented, but rates for other acute upper respiratory tract infections of interest have declined.CONCLUSIONS: The Do Bugs Need Drugs? program significantly improves physician antibiotic prescription decisions and is ecologically associated with desirable change in population antibiotic consumption patterns.

BACKGROUND: Antibiotic consumption in human populations is one of the factors responsible for the emergence of resistant organisms. It is important to track population-based data on an ongoing basis, and to explore the determinants of regional variation in antibiotic consumption.METHODS: Population-level data were obtained on all outpatient oral antibiotic prescriptions dispensed within British Columbia (BC) between 1996 and 2007. Prescriptions were expressed as the defined daily dose per 1000 inhabitants. Geographical information systems mapping was used to display the spatial variations of antibiotic consumption in BC. The relationships among antibiotic consumption, socioeconomic factors and climatic conditions were explored using Pearson’s correlation and regression modelling.RESULTS: Overall antibiotic consumption was highest in the northern regions of BC. Higher rates of consumption were associated with a greater proportion of the Aboriginal population, lower levels of education and individuals younger than 15 years of age. An inverse correlation was found between some classes of antibiotics and the following factors: individuals older than 65 years of age, mortality rate, doctor-to-population ratio, household size and higher July temperatures. The adjusted regression analyses indicated that higher antibiotic consumption was associated with a higher proportion of Aboriginals and household income.CONCLUSION: Different rates of antibiotic consumption exist within BC. The use of antibiotics is correlated with several socioeconomic factors and climatic conditions. It may be useful to consider these factors when designing policies to address antibiotic consumption in the community.

Varicella-zoster virus reactivation leads to herpes zoster – the main complication of which is postherpetic neuralgia (PHN). Rapid antiviral therapy initiated within 72 h of rash onset has been shown to accelerate rash healing, reduce the duration of acute pain and, to some extent, attenuate the development and duration of PHN. Other adjunctive therapies such as analgesics, antidepressants and some anticonvulsants are frequently required in the management of severe PHN. A live, attenuated zoster vaccine has been recently shown to significantly decrease herpes zoster incidence, PHN and the overall burden of illness when administered to adults older than 60 years of age. This new prophylactic modality has been reported to be cost-effective in the Canadian context, especially in the 60- to 75-year-old age group.

Two major outbreaks of invasive meningococcal disease serogroup C (IMD-C) were identified in British Columbia between 2000 and 2004. Pulsed-field gel electrophoresis (PFGE) and porA gene sequencing of all retained IMD-C isolates were used to assess correlations between genotypes and epidemiological patterns. PFGE patterns of IMD-C genotypes correlated with epidemiological patterns between 2000 and 2004 in British Columbia, and demonstrated that PFGE can identify outbreak-related cases. Both IMD-C outbreaks correlated with a respective PFGE pattern. PFGE analysis demonstrated that the 2004 British Columbia outbreak strain in men who have sex with men was closely related to the 2001 Abbotsford outbreak strain. PorA sequencing data indicated low diversity of class 1 outer membrane proteins in British Columbia, and did not correlate with epidemiological trends. There was a trend for outbreak-associated PFGE types to demonstrate higher case fatality rates.

BACKGROUND: In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV).METHODS: Cases at a care facility were epidemiologically characterized and sequentially investigated for conventional agents of respiratory infection, SARS-CoV and other human CoVs. Serological cross-reactivity between SARS-CoV and human CoV-OC43 (HCoV-OC43) was investigated by peptide spot assay.RESULTS: Ninety-five of 142 residents (67%) and 53 of 160 staff members (33%) experienced symptoms of respiratory infection. Symptomatic residents experienced cough (66%), fever (21%) and pneumonia (12%). Eight residents died, six with pneumonia. No staff members developed pneumonia. Findings on reverse transcriptase-polymerase chain reaction assays for SARS-CoV at a national reference laboratory were suspected to represent false positives, but this was confounded by concurrent identification of antibody to N protein on serology. Subsequent testing by reverse transcriptase-polymerase chain reaction confirmed HCoV-OC43 infection. Convalescent serology ruled out SARS. Notably, sera demonstrated cross-reactivity against nucleocapsid peptide sequences common to HCoV-OC43 and SARS-CoV.CONCLUSIONS: These findings underscore the virulence of human CoV-OC43 in elderly populations and confirm that cross-reactivity to antibody against nucleocapsid proteins from these viruses must be considered when interpreting serological tests for SARS-CoV.

BACKGROUND: A relationship between Chlamydia pneumoniae infection and acute coronary syndromes has not been consistently found in published studies. It has been hypothesized that a bacteriophage-infected subset of C pneumoniae may be uniquely equipped to promote atherosclerosis and acute coronary syndromes through the expression of phage genes. METHODS: The authors performed a pilot case-control study of acute coronary events. Case and control subjects were characterized demographically and according to recognized coronary risk factors. These subjects also provided serum for the detection of antibody to the elementary bodies of C pneumoniae and antibody to the Vp1 protein coded by the phage. Bivariate and multivariate comparisons were performed using statistics appropriate for paired analyses. RESULTS: Antibodies to C pneumoniae, Vp1 protein or both were not associated with acute coronary events by bivariate or multivariate analysis. As expected, case subjects were significantly more likely to have hypertension, hypercholesterolemia or diabetes mellitus. CONCLUSION: The present study adds to a growing body of literature that does not support the hypothesized relationship between C pneumoniae (or a phage-infected subset of C pneumoniae) and acute coronary syndromes.

Despite the global public health importance of resistance of microorganisms to the effects of antibiotics, and the direct relationship of consumption to resistance, little information is available concerning levels of consumption in Canadian hospitals and out-patient settings. The present paper provides practical advice on the use of administrative pharmacy data to address this need. Focus is made on the use of the Anatomical Therapeutic Chemical classification and Defined Daily Dose system. Examples of consumption data from Canadian community and hospital settings, with comparisons to international data, are used to incite interest and to propose uses of this information. It is hoped that all persons responsible for policy decisions regarding licensing, reimbursement, prescribing guidelines, formulary controls or any other structure pertaining to antimicrobial use become conversant with the concepts of population antibiotic consumption and that this paper provides them with the impetus and direction to begin accurately measuring and comparing antibiotic use in their jurisdictions.

BACKGROUND: This study examined the epidemiology, antibiotic susceptibility and serotype distribution of Streptococcuspneumoniae associated with invasive pneumococcal disease (IPD) in British Columbia.METHODS: Six hospitals and one private laboratory network participated in a prospective, sentinel laboratory based surveillance study of IPD, between October 1999 and October 2000. At each site, S pneumoniae isolates were collected and epidemiological data were gathered using a structured questionnaire, for all cases of IPD meeting the study case definition. Isolates were serotyped and tested for antimicrobial susceptibility. Bivariate associations were analyzed and multivariate logistic regression was used to identify independent risk factors associated with hospitalization or death.RESULTS: One hundred three reports and isolates were collected. Seventy-nine per cent of cases were community-acquired, 64% required hospitalization and 5% died. Cases with one or more assessed risk factor for IPD and of female sex were independent variables associated with hospitalization or death. One-third of isolates had reduced penicillin susceptibility and 96% of these represented serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV-23). Overall, 89% of serotypes identified are included in the PPV-23 vaccine and 88% of isolates from children under five years of age are found in the 7-valent pneumococcal conjugate vaccine (PCV-7). Forty-one per cent of cases qualified for publicly funded pneumococcal vaccine and 34% of eligible persons were vaccinated.CONCLUSIONS: Overall, pneumococcal serotypes associated with IPD in this study closely matched serotypes included in PPV-23 products currently licensed in Canada. Most serotypes associated with IPD in children under five years of age are included in a recently licenced PCV-7. One third of isolates demonstrated reduced penicillin susceptibility, most involving serotypes included in PPV-23. Effective delivery of current public health immunization programs using PPV-23 and extending protection to infants and young children using the PCV-7 will prevent many cases of IPD.

OBJECTIVE: To assess the cost effectiveness of azithromycin versus doxycycline therapy for cervical Chlamydia trachomatis infections in Canada.DESIGN: A predictive decision analytic model using previously published clinical and economic evaluations, expert opinion and costs of medical care in Canada.POPULATION: A hypothetical cohort of 5000 women followed over 10 years.INTERVENTIONS: Two diagnostic strategies were compared, laboratory confirmed diagnosis (LCD) and presumptive diagnosis (PD) of C trachomatis infection. Under each strategy, two treatment alternatives were analyzed, a single 1 g dose of azithromycin and a seven-day course of doxycycline as 100 mg twice daily.RESULTS: Despite a fourfold higher acquisition cost, under base case conditions, for both diagnostic strategies, the azithromycin treatment alternative was more cost effective than the doxycycline alternative. For the LCD model, the cost per cure for patients receiving azithromycin was $184.76 compared with $240.59 for patients receiving doxycycline, resulting in an incremental cost of $55.83. For the PD model, the cost per cure for patients treated with azithromycin was $51.48 compared with $51.82, resulting in an incremental cost of $0.34. For the hypothetical cohort of 5000 women, the use of azithromycin translates into a projected annual cost savings of $279,150 and $1,700 for the LCD and PD models, respectively. In one-way sensitivity analyses for the LCD model, no clinically plausible changes in the base case estimates changed the results of the cost effectiveness outcome. In the PD model, clinically plausible changes in the probabilities of doxycycline cure, pelvic inflammatory disease, sequelae and chlamydia infection were found to alter the cost effectiveness outcome.CONCLUSIONS: Based on the results from our model, the azithromycin strategy should be employed for the treatment of laboratory confirmed cases. However, for presumptive cases, azithromycin should be used only if the probabilities of C trachomatis and pelvic inflammatory disease are more than 19%, doxycycline effectiveness is less than 78%, or the cost of azithromycin is less than $19.00.