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BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with considerable morbidity and mortality, especially with persistent (PB) or recurrent bacteremia (RB).OBJECTIVE: To determine the frequency of PB and RB in patients with MRSA BSI, and to characterize the isolates from these patients.METHODS: Surveillance for MRSA BSI was performed for one year in 13 Canadian hospitals. PB was defined as a positive blood culture that persisted for ≥7 days; RB was defined as the recurrence of a positive blood culture ≥14 days following a negative culture. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Vancomycin susceptibility was determined using Etest.RESULTS: A total of 183 patients with MRSA BSI were identified; 14 (7.7%) had PB and five (2.7%) had RB. Ten (5.5%) patients were known to have infective endocarditis, and five of these patients had PB or RB. Initial and subsequent MRSA isolates from patients with PB and RB had the same PFGE type. There were no significant differences in the distribution of PFGE types in patients with PB or RB (37% CMRSA-2/USA100; 37% CMRSA-10/USA300) compared with that in other patients (56% CMRSA-2/USA100; 32% CMRSA-10/USA300). All isolates were susceptible to vancomycin, but patients with PB or RB were more likely to have initial isolates with vancomycin minimum inhibitory concentration = 2.0 μg/mL (26% versus 10%; P=0.06).CONCLUSIONS: Persistent or recurrent MRSA bacteremia occurred in 10.4% of patients with MRSA BSIs. Initial isolates from patients with persistent or recurrent MRSA BSIs were more likely to exhibit reduced susceptibility to vancomcyin, but were not associated with any genotype.

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: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]).METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens.RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 μg/mL or greater and 1.0 μg/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable.CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine.

INTRODUCTION: While Staphylococcus aureus is an uncommon but serious cause of traditional community-acquired pneumonia (CAP), it is a predominant cause of nosocomial pneumonia in addition to the unique clinical entity of health care-associated pneumonia (HCAP). A cohort of bacteremic S aureus pneumonia cases was reviewed to determine the role of HCAP among the cohort, and to assess for differences between CAP and HCAP.PATIENTS AND METHODS: Bacteremic S aureus pneumonia cases were identified from a prospective study of all patients diagnosed with CAP who presented to hospitals in Edmonton, Alberta, between November 2000 and November 2002. These cases were subsequently reviewed retrospectively. Demographic, clinical and microbiological data were obtained, and patients were classified as having CAP or HCAP. Relatedness of isolates was determined by pulsed-field gel electrophoresis analysis in conjunction with epidemiological information.RESULTS: There were 28 cases of bacteremic S aureus pneumonia identified. Fifty-seven per cent were reclassified as having HCAP, and 43% remained classified as having CAP. The CAP cohort was significantly younger than the HCAP cohort (mean age 49.0±23.7 years versus 67.8±18.6 years; P=0.035) with higher rates of intravenous drug use (50% versus 0%; P=0.002). Long-term care facility residence (44%) was common in the HCAP cohort. The HCAP cohort presented with more severe illness, having a higher mean pneumonia severity index score (143.1±41.1 versus 98.2±54.6; P=0.028), and despite fewer embolic complications, there was a trend toward a significantly higher mortality rate (31% versus 0%; P=0.052). Two community-acquired isolates cultured in the setting of intravenous drug use were methicillin-resistant, and no isolates were positive for Panton-Valentine leukocidin. There was evidence of relatedness involving 44% of the HCAP isolates by pulsed-field gel electrophoresis analysis.CONCLUSION: HCAP accounts for a significant number of cases that, when using traditional definitions, would be classified as CAP. Severity of illness and mortality was excessive within the HCAP group. There was evidence of relatedness and spread of common strains in the HCAP cohort. The present study supports recommendations for treatment guidelines directed toward the entity of HCAP and the empirical coverage of S aureus among certain high-risk groups.

BACKGROUND: The frequency of Chlamydia trachomatis and Neisseria gonorrhoeae coinfection can vary depending on their individual incidence and prevalence rates.OBJECTIVE: To determine the frequency of C trachomatis and N gonorrhoeae coinfections by evaluating the results of testing in 2007 and 2008 to better inform testing and treatment decisions.METHODS: Specimens from the same patient submitted on the same day served as the basis for the present study. The age, sex and the source of the specimen were also linked to the accession number. Infection and coinfection rates were analyzed in both males and females.RESULTS: Concurrent testing was performed on 41,567 female specimens and 1827 male specimens, of which, 1495 female samples (3.6%) tested positive for C trachomatis infection and 88 (0.2%) tested positive for N gonorrhoeae infections. Only 31 females were coinfected; however, for those between 11 and 25 years of age, 25 of 61 females (40.1%) with N gonorrhoeae infection also tested positive for C trachomatis infection; conversely, 25 of 1248 females (2.0%) with C trachomatis infection also tested positive for N gonorrhoeae infection. For males, 213 (11.7%) tested positive for C trachomatis infection, and 59 (3.2%) tested positive for N gonorrhoeae infection. In 30 males with N gonorrhoeae between 11 and 25 years of age, and 149 males with C trachomatis, eight coinfections were observed (26.7% and 5.3%, respectively). Of those older than 25 years of age, only five of 905 men and six of 19,465 women were coinfected. None of the 10,935 women who were 30 years of age or older had coinfections.CONCLUSION: The N gonorrhoeae coinfection rate in males with C trachomatis may justify empirical antimicrobials; however, in females, the proportion of coinfected may not justify empirical treatment for N gonorrhoeae infection when the C trachomatis test is positive and N gonorrhoeae testing has not been performed.

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.

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.

HIV diagnostic testing has come a long way since its inception in the early 1980s. Current enzyme immunoassays are sensitive enough to detect antibody as early as one to two weeks after infection. A variety of other assays are essential to confirm positive antibody screens (Western blot, polymerase chain reaction [PCR]), provide an adjunct to antibody testing (p24 antigen, PCR), or provide additional information for the clinician treating HIV-positive patients (qualitative and quantitative PCR, and genotyping). Most diagnostic laboratories have complex testing algorithms to ensure accuracy of results and optimal use of laboratory resources. The choice of assays is guided by the initial screening results and the clinical information provided by the physician; both are integral to the laboratory's ability to provide an accurate laboratory diagnosis. Laboratories should also provide specific information on specimen collection, storage and transport so that specimen integrity is not compromised, thereby preserving the accuracy of laboratory results. Point of Care tests have become increasingly popular in the United States and some places in Canada over the past several years. These tests provide rapid, on-site HIV results in a format that is relatively easy for clinic staff to perform. However, the performance of these tests requires adherence to good laboratory quality control practices, as well as the backup of a licensed diagnostic laboratory to provide confirmation and resolution of positive or indeterminate results. Laboratory quality assurance programs and the participation in HIV proficiency testing programs are essential to ensure that diagnostic laboratories provide accurate, timely and clinically relevant laboratory results.

Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.