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6.  Respiratory infection and otitis media visits in relation to pneumococcal conjugate vaccine use in Saskatchewan 
BACKGROUND:
In Saskatchewan, pneumococcal conjugate vaccination (PCV) was offered to high-risk children in 2002 and to all infants in 2005.
OBJECTIVE:
To describe trends in the frequency of medical visits for lower respiratory tract infection (LRI) and otitis media (OM) in relation to PCV use during the period 1990 to 2008.
METHODS:
Statistics regarding the number of children covered by the health insurance plan, PCV administration, and medical visits with a diagnostic code associated with LRI and OM were provided by Saskatchewan Health. Monthly rates were analyzed using dynamic state space models.
RESULTS:
In all series, there was a marked seasonal cycle and some higher-than-expected winter peak values, possibly associated with epidemics of specific respiratory viruses. Three abrupt decreases in baseline rate were observed for LRI and the final one, in February 2007, could be related to the increased proportion of children vaccinated with PCV. There was no statistical correlation between PCV use and OM visit frequency.
CONCLUSION:
Many environmental, biological and administrative factors may influence health services use, and an effect of low magnitude of a particular vaccine pertaining to nonspecific outcomes could be obscured in time-series analyses.
PMCID: PMC3904999  PMID: 24489558
Otitis media; Pneumococcal conjugate vaccine; Pneumonia; Program evaluation
7.  Reduction of central line-associated bloodstream infection rates in a neonatal intensive care unit after implementation of a multidisciplinary evidence-based quality improvement collaborative: A four-year surveillance 
BACKGROUND:
The use of central venous catheters has permitted lifesaving treatment for critically ill neonates; however, the attributable mortality rate for central line-associated bloodstream infections (CLABSIs) has been estimated to be between 4% and 20%. In 2006/2007, the authors’ neonatal intensive care unit (NICU) had a CLABSI rate that was nearly twofold higher than that reported by other Canadian NICUs.
OBJECTIVE:
To implement a quality improvement collaborative to reduce the incidence of neonatal CLABSI.
METHODS:
A retrospective observational study was performed to compare CLABSI in neonates admitted to the authors’ level III NICU between August 2007 and March 2011. The entire study period was divided into four time periods to evaluate secular trends. A comprehensive catheter-related bloodstream infection prevention initiative was implemented in August 2007. The initiatives included staff education, standardization of skin preparation protocol, introduction of new antiseptic agents, implementation of central catheter insertion and maintenance checklists, reinforcement of the use of maximal sterile barrier precautions, and revision of the central catheter configuration and maintenance protocols.
RESULTS:
The median CLABSI rate of 7.9 per 1000 catheter days at the beginning of the study (period 1 [August 2007 to June 2008]) gradually decreased over the entire study period (P=0.034): period 2 (July 2008 to May 2009), 3.3 per 1000 catheter days; period 3 (June 2009 to April 2010), 2.6 per 1000 catheter days; and period 4 (May 2010 to March 2011), 2.2 per 1000 catheter days.
CONCLUSION:
A multidisciplinary evidence-based quality improvement collaborative resulted in a significant reduction in the CLABSI rate. Continuous quality improvement measures are required to reduce catheter-related bloodstream infections among low-birth-weight infants.
PMCID: PMC3905000  PMID: 24489559
Bloodstream infection; Central line; Neonate
8.  Evaluation of MALDI-TOF mass spectrometry and Sepsityper Kit™ for the direct identification of organisms from sterile body fluids in a Canadian pediatric hospital 
Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) can be used to identify bacteria directly from positive blood and sterile fluid cultures. The authors evaluated a commercially available kit – the Sepsityper Kit (Bruker Daltonik, Germany) – and MALDI-TOF MS for the rapid identification of organisms from 80 flagged positive blood culture broths, of which 73 (91.2%) were blood culture specimens and seven (8.7%) were cerebrospinal fluid specimens, in comparison with conventional identification methods. Correct identification to the genus and species levels was obtained in 75 of 80 (93.8%) and 39 of 50 (78%) blood culture broths, respectively. Applying the blood culture analysis module, a newly developed software tool, improved the species identification of Gram-negative organisms from 94.7% to 100% and of Gram-positive organisms from 66.7% to 70%.
MALDI-TOF MS is a promising tool for the direct identification of organisms cultured from sterile sites.
PMCID: PMC3905001  PMID: 24489560
Blood cultures; Blood culture analysis module; Direct identification; MALDI-TOF MS
9.  Influenza immunization practices and policies for health care students in Canada 
BACKGROUND:
Influenza vaccine is recommended for all health care providers including health care students. Little is known about how health care student programs provide information about influenza vaccination to their students, deliver vaccines and document their vaccination status.
METHODS:
A mixed-methods approach was used and included key informant interviews of program coordinators for health care student programs in Halifax (Nova Scotia) and a national survey of program coordinators of health care student programs across Canada.
RESULTS:
All 21 coordinators of programs that had students placed at the IWK Health Centre (Halifax, Nova Scotia) during the influenza season were interviewed. Surveys were completed by 93 (36.3%) of 256 eligible coordinators representing 134 different programs (response rate 52.3%). Most programs encouraged seasonal influenza vaccination but only 28 (20.9%) required it. None of the Halifax programs delivered influenza vaccine and most preferred a coordinated, centrally administered program. In contrast, many programs across Canada delivered influenza vaccine and did not desire a centralized process.
CONCLUSION:
There is considerable variability in the delivery of influenza vaccine to health care students across Canada. Coordinated programs may be desirable where delivery programs do not already exist.
PMCID: PMC3905002  PMID: 24489561
Health care students; Immunization policy; Influenza vaccine
10.  HIV-1 tropism testing and clinical management of CCR5 antagonists: Quebec review and recommendations 
HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.
PMCID: PMC3905003  PMID: 24489562
CCR5; HIV; Maraviroc; Tropism
11.  ‘Bobo-Newton syndrome’: An unwanted gift from man’s best friend 
Capnocytophaga canimorsus is a facultative Gram-negative bacillus that is typically a constituent of the oral flora of dogs and cats. It was first isolated by Bobo and Newton in 1976 from a man presenting with meningitis following a dog bite. Transmission to humans follows various animal-related injuries, which may be gross or subtle. C canimorsus can cause a spectrum of syndromes ranging from skin and soft tissue infection to invasive disease such as meningitis or endocarditis. The present article reports a case of C canimorsus meningitis in a patient with the classic risk factor of alcoholic liver cirrhosis. Clinical suspicion was confirmed by culture and genetic identification of the blood isolate. The present article reviews the Capnocytophaga genus, the clinical syndromes most commonly associated with this zoonotic organism, its laboratory identification and treatment.
PMCID: PMC3905004  PMID: 24489563
Capnocytophaga canimorsus; Dog bite; Gram-negative bacillus; Meningitis
12.  Artemisinin combination therapy can result in clinical failure if oral therapy is not directly observed 
Intravenous artesunate therapy is the first-line therapy for severe malaria, and is highly efficacious when used in combination with an oral partner drug such as doxycycline or atovaquone-proguanil. However, treatment failure occurs routinely with artesunate monotherapy due to the very short half-life of this drug. In North America, experience with artesunate is limited. With the pressure to discharge patients early, administration of the essential oral partner drug is often left to the discretion of the patient. Thus, treatment failure may be commonplace if nonadherence is a factor, as was observed in the case described in the present report.
PMCID: PMC3905005  PMID: 24489564
Adherence; Artesunate; Malaria; Plasmodium falciparum; Treatment failure
13.  CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core: Canadian guidelines for management and treatment of HIV/hepatitis C coinfection in adults 
BACKGROUND:
Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.
OBJECTIVE:
To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context.
METHODS:
A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale.
RESULTS:
All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2–6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients.
DISCUSSION:
Recommendations may not supersede individual clinical judgement.
PMCID: PMC3905006  PMID: 24489565
Antivirals; Direct-acting antivirals; HCV; HIV; Pharmacokinetics
14.  Comparison of clinical and epidemiological features of Shiga toxin-producing Escherichia coli O157 and non-O157 infections in British Columbia, 2009 to 2011 
INTRODUCTION:
Shiga toxin-producing Escherichia coli (STEC) are major foodborne agents that have the potential to cause severe enteric illnesses and large outbreaks worldwide. Several studies found non-O157 infections to be clinically milder than O157 STEC infections.
OBJECTIVE:
To compare the clinical and epidemiological profiles of O157 and non-O157 STEC human infections in British Columbia (BC).
METHODS:
All STEC cases reported in BC from 2009 to 2011 by four local health authorities were included in the study. Cases were classified according to STEC serotype based on laboratory information. Information was gathered via case interview forms. Data analysis included the χ2 test and Mann-Whitney test; P<0.05 was considered to be statistically significant.
RESULTS:
A total of 260 STEC cases were reported, including 154 (59.2%) O157 cases, 63 (24.2%) non-O157 cases and 43 (16.5%) STEC cases with no serotype identified. Hospitalization rate was higher and duration of hospitalization was significantly longer for O157 cases compared with non-O157 cases, but other clinical features were not significantly different. Patients with non-O157 infections were significantly more likely to have travelled outside Canada, less likely to report food exposure at social gatherings and more likely to consume bagged greens and cheese.
DISCUSSION:
O157 is the predominant O serotype in BC and appeared to be more clinically severe than non-O157 STEC infections. However, the true incidence and severity of non-O157 remain unknown due to our current inability to detect all non-O157 cases. The present study and the literature suggest the need to identify more predictive virulence factors because serotype does not consistently predict disease severity.
PMCID: PMC3905009  PMID: 24489568
Clinical severity; Enteric illness; Epidemiological profile; O157 serotype; STEC
15.  Macrolide use in the treatment of critically ill patients with pneumonia: Incidence, correlates, timing and outcomes 
BACKGROUND:
Macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. Evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties.
OBJECTIVE:
To evaluate the incidence, correlates, timing and mortality associated with macrolide-based treatment.
METHODS:
A population-based cohort of critically ill adults with pneumonia at five intensive care units in Edmonton, Alberta, was prospectively followed over two years. Data collected included disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score), pneumonia severity (Pneumonia Severity Index score), comorbidities, antibiotic treatments at presentation and time to effective antibiotic. The independent association between macrolide-based treatment and 30-day all-cause mortality was examined using multivariable Cox regression. A secondary exploratory analysis examined time to effective antimicrobial therapy.
RESULTS:
The cohort included 328 patients with a mean Pneumonia Severity Index score of 116 and a mean APACHE II score of 17; 84% required invasive mechanical ventilation. Ninety-one (28%) patients received macrolide-based treatments, with no significant correlates of treatment except nursing home residence (15% versus 30% for nonresidents [P=0.02]). Overall mortality was 54 of 328 (16%) at 30 days: 14 of 91 (15%) among patients treated with macrolides versus 40 of 237 (17%) for nonmacrolides (adjusted HR 0.93 [95% CI 0.50 to 1.74]; P=0.8). Patients who received effective antibiotics within 4 h of presentation were less likely to die than those whose treatment was delayed (14% versus 17%; adjusted HR 0.50 [95% CI 0.27 to 0.94]; P=0.03).
CONCLUSIONS:
Macrolide-based treatment was not associated with lower 30-day mortality among critically ill patients with pneumonia, although receipt of effective antibiotic within 4 h was strongly predictive of survival. Based on these results, timely effective treatment may be more important than choice of antibiotics.
PMCID: PMC3905010  PMID: 24489569
Critical care; Intensive care; Lung; Macrolides; Mortality; Pneumonia
16.  Evaluation of MRSASelect™ chromogenic medium for the early detection of methicillin-resistant Staphylococcus aureus from blood cultures 
INTRODUCTION:
Staphylococcus aureus bacteremia is associated with considerable morbidity and mortality. In theory, reducing the turnaround time in reporting of methicillin-resistant S aureus (MRSA) among patients with bactermia could assist with the rapid optimization of antimicrobial therapy.
OBJECTIVE:
To evaluate the sensitivity and specificity of MRSASelect (Bio-Rad Laboratories, USA), a chromogenic medium, in the early detection of MRSA from blood cultures growing Gram-positive cocci in clusters, and to confirm that routine use of this medium would, in fact, reduce turnaround time for MRSA identification.
METHODS:
The present study was conducted at three microbiology laboratories in Manitoba. Between April 2010 and May 2011, positive blood cultures with Gram-positive cocci in clusters visualized on Gram stain were subcultured to both MRSASelect and routine media. MRSA isolates were identified using conventional microbiological methods from routine media and using growth with the typical colony morphology (pink colony) on MRSASelect medium.
RESULTS:
A total of 490 blood cultures demonstrating Gram-positive cocci in clusters on Gram stain were evaluated. S aureus was recovered from 274 blood cultures, with 51 S aureus isolates (51 of 274 [18.6%]) identified as MRSA. MRSASelect medium had a sensitivity of 98%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 99.8% for the recovery and identification of MRSA directly from positive blood culture bottles. In addition, use of MRSASelect medium was found to improve turnaround time in the detection of MRSA by almost 24 h relative to conventional methods.
DISCUSSION:
These data support the utility of MRSASelect medium for the rapid identification of MRSA from positive blood cultures. Further clinical studies are warranted to determine whether the improvement in turnaround time will result in a measurable reduction in suboptimal antimicrobial therapy and/or improvement in patient outcome.
PMCID: PMC3905011  PMID: 24489570
Blood cultures; Chromogenic agar; MRSA; Staphylococcus aureus
17.  Prevalence and incidence of antimicrobial-resistant organisms among hospitalized inflammatory bowel disease patients 
BACKGROUND:
Patients with inflammatory bowel disease (IBD) experience frequent hospitalizations and use of immunosuppressive medications, which may predispose them to colonization with antimicrobial-resistant organisms (ARO).
OBJECTIVE:
To determine the prevalence of ARO colonization on admission to hospital and the incidence of infection during hospitalization among hospitalized IBD patients.
METHODS:
A chart review comparing the prevalence of colonization and incidence of infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL) in hospitalized IBD patients with those of non-IBD controls was performed.
RESULTS:
On admission, there were no significant differences between IBD inpatients and controls in the prevalence of colonization of methicillin-resistant S aureus (1.0% versus 1.2%; P=0.74), vancomycin-resistant enterococci (0.2% versus 0%; P=1.0) or ESBL (4.1% versus 5.5%; P=0.33). Pooling data from historical clinic-based cohorts, IBD patients were more likely than controls to have ESBL colonization (19% versus 6.6%; P<0.05). Antibiotic use on admission was associated with ESBL colonization among IBD inpatients (OR 4.2 [95% CI 1.4 to 12.6]). The incidence of ARO infections during hospitalization was not significantly different between IBD patients and controls. Among IBD patients who acquired ARO infections during hospitalizations, the mean time interval from admission to infection was shorter for those who were already colonized with ARO on admission.
CONCLUSIONS:
This particular population of hospitalized IBD patients was not shown to have a higher prevalence or incidence of ARO colonization or infection compared with non-IBD inpatients.
PMCID: PMC3905012  PMID: 24489571
Crohn disease; Extended spectrum beta-lactamase; Inflammatory bowel disease; Methicillin-resistant Staphylococcus aureus; Ulcerative colitis; Vancomycin-resistant enterococci
21.  Micafungin compared with caspofungin for the treatment of febrile episodes in neutropenic patients with hematological malignancies: A retrospective study 
Patients with neutropenia resulting from chemotherapy for hematological malignancies are at risk for considerable morbidity and mortality due to invasive fungal infections and should, thus, be treated with antifungal agents. Caspofungin has been one of the most common antifungal agents used for this purpose; its analogue micafungin may also be appropriate, but has not been tested as extensively. Accordingly, the authors of this article conducted a retrospective study to compare these two agents; the results contribute to the literature regarding the use of micafungin for the treatment of invasive fungal infections.
BACKGROUND:
Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia.
METHODS:
A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria, with modification of the diagnostic imaging criteria.
RESULTS:
Micafungin had similar overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82], respectively; P=0.729). Survival was higher in the micafungin group compared with the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No baseline invasive fungal infections were identified in the micafungin group, compared with three proven infections treated successfully with caspofungin (3.7%; P=0.18). Three proven breakthrough infections were observed in the micafungin group (three of 48 [27.3%]) compared with none in the caspofungin group (zero of 82; P=0.02).
CONCLUSION:
Micafungin has similar efficacy to caspofungin as empirical antifungal therapy in febrile neutropenic patients with hematological malignancies. Verification of these results in a prospective trial is warranted.
PMCID: PMC4277157  PMID: 25587291
Echinocandins; Fungal; Infection; Leukemia; Neutropenia
22.  Triage and protocol recommendations for the parasitology laboratory based on an epidemiological investigation of parasite diagnostics in Ontario laboratories 
Parasitic infections associated with gastroenteritis can cause considerable morbidity and mortality, and may be endemic or nonendemic in Ontario. Recently, there have been developments in laboratory protocols for identifying such parasites. The authors of this study used retrospective data from a single laboratory sector in Ontario to develop protocols for the diagnosis of parasitic infections, and also assessed risk factors associated with these infections.
OBJECTIVES:
A study was performed using a subset of Ontario laboratory parasitology data, with three objectives: to describe parasitic infections in Ontario; to identify risk factors for acquiring a parasitic infection using routinely collected information; and to use this information to assess current protocols for parasite testing in laboratories and, in turn, to propose alternatives to optimize the allocation of laboratory resources.
METHODS:
All parasitology records from January 4, 2010 to September 14, 2010 were reviewed descriptively and risk factor analyses were performed using information collected from requisitions. These results were used to develop preliminary alternative protocols, which considered high-throughput screening tests and inclusion/exclusion criteria for ova and parasite testing; these were then retrospectively analyzed with the dataset to determine appropriateness.
RESULTS:
Of the 29,260 records analyzed, 10% were multiple samples from single patients submitted on the same day, of which 98% had the same result. Three percent of all parasite tests were positive, with the most prevalent parasites being (in ascending order) Dientamoeba fragilis, Giardia lamblia, Cryptosporidium species and Entamoeba histolytica/dispar. Age and sex were found to be weak risk factors, while rural living was found to be a moderate risk factor for D fragilis, G lamblia and Cryptosporidium infections. The strongest risk factor was travel history, especially for nonendemic parasites. The retrospective analysis of six alternative protocols identified four that may be more efficient than current procedures.
CONCLUSIONS:
The present study demonstrated that current protocols may be redundant and can be optimized to target prevalent parasites and populations with high risk factors.
PMCID: PMC4277158  PMID: 25587292
Diagnosis; Parasitic infection; Risk factor
23.  CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults 
Treatment of HIV-hepatitis C virus (HCV)-coinfected individuals is considerably more complex than the treatment of monoinfected individuals, due to several factors including interactions among medications and accelerated progression of liver disease. Since the first Canadian guidelines for the treatment of HIV-HCV coinfected patients were published in the Winter 2013 issue of the Journal, several new medications that show considerable promise for the treatment of HCV have become available in Canada. Thus, the authors provide an update to the 2013 guidelines and include updated recommendations for treatment that incorporate these new medications.
BACKGROUND:
Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.
OBJECTIVE:
To update national standards for the management of HCV-HIV coinfected adults in the Canadian context.
METHODS:
A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines.
RESULTS:
Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment.
DISCUSSION:
Recommendations may not supersede individual clinical judgement.
PMCID: PMC4277159  PMID: 25587293
Antivirals; Coinfection; HCV; HIV; Treatment; Updated guidelines

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