Allison McGeer

Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality.

BACKGROUNDnC. difficile infection (CDI) has become an important and frequent nosocomial infection, often resulting in severe morbidity or death. Severe CDI is more frequently seen among individuals infected with the emerging NAP1/027/BI (NAP1) strain and in the elderly population, but the relative importance of these 2 factors remains unclear. We used a large Canadian database of patients with CDI to explore the interaction between these 2 variables.nnnMETHODSnThe Canada-wide CDI study, performed in 2005 by the Canadian Nosocomial Infection Surveillance Program (CNISP), was used to analyze the role of infecting strain type and patient age on the severity of CDI. A severe outcome was defined as CDI requiring intensive care unit care, colectomy, or causing death (directly or indirectly) within 30 days after diagnosis.nnnRESULTSnA total of 1008 patients in the CNISP database had both complete clinical data and infecting strain analysis documented. A total of 311 patients (31%) were infected with the NAP1 strain, 83 (28%) were infected with the NAP2/J strain, and the rest were infected with various other types. The proportion of NAP1 infections correlated with the incidence and the severity of CDI when analyzed by province. Thirty-nine (12.5%) of the infections due to the NAP1 strain resulted in a severe outcome, compared with only 41 (5.9%) of infections due to the other types (P < .001). The patients age was strongly associated with a severe outcome, and patients 60-90 years of age were approximately twice as likely to experience a severe outcome if the infection was due to NAP1, compared with infections due to other types.nnnCONCLUSIONSnOur study confirms the strong age association with infection due to the NAP1 strain and severe CDI. In addition, patients 60-90 years of age infected with NAP1 are approximately twice as likely to die or to experience a severe CDI-related outcome, compared with those with non-NAP1 infections. Patients >90 years of age experience high rates of severe CDI, regardless of strain type.

Health Care-Associated Clostridium difficile Infection in Adults Admitted to Acute Care Hospitals in Canada: A Canadian Nosocomial Infection Surveillance Program Study

BACKGROUNDnClostridium difficile infection (CDI) is the most frequent cause of health care-associated infectious diarrhea in industrialized countries. The only previous report describing the incidence of health care-associated CDI (HA CDI) in Canada was conducted in 1997 by the Canadian Nosocomial Infection Surveillance Program. We re-examined the incidence of HA CDI with an emphasis on patient outcomes.nnnMETHODSnA prospective surveillance was conducted from 1 November 2004 through 30 April 2005. Basic demographic data were collected, including age, sex, type of patient ward where the patient was hospitalized on the day HA CDI was identified, and patient comorbidities. Data regarding severe outcome were collected 30 days after the diagnosis of HA CDI; severe outcome was defined as an admission to the intensive care unit because of complications of CDI, colectomy due to CDI, and/or death attributable to CDI.nnnRESULTSnA total of 1430 adults with HA CDI were identified in 29 hospitals during the 6-month surveillance period. The overall incidence rate of HA CDI for adult patients admitted to these hospitals was 4.6 cases per 1000 patient admissions and 65 per 100,000 patient-days. At 30 days after onset of HA CDI, 233 patients (16.3%) had died from all causes; 31 deaths (2.2%) were a direct result of CDI, and 51 deaths (3.6%) were indirectly related to CDI, for a total attributable mortality rate of 5.7%.nnnCONCLUSIONSnThe rates are remarkably similar to those found in our previous study; although we found wide variations in HA CDI among the participating hospitals. However, the attributable mortality increased almost 4-fold (5.7% vs. 1.5%; P<.001).

Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach

Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by group A streptococci (GAS). GAS is also an important cause of necrotizing fasciitis, for which an early and extensive surgical intervention is currently advocated. Here we report on the use of an aggressive medical regimen including high-dose IVIG together with a conservative surgical approach in severe GAS soft tissue infection. We describe 7 patients with severe soft tissue infection caused by GAS, who all were treated with effective antimicrobials and high-dose IVIG. Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. All patients survived. Immunostaining of tissue biopsies from 2 of the patients revealed high levels of GAS, superantigen and pro-inflammatory cytokines initially, which were dramatically reduced in a repeat biopsy of the initial operative site collected from 1 of the patients 66 h post-IVIG administration. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow an initial non-operative or minimally invasive approach, which can limit the need to perform immediate wide debridements and amputations in unstable patients.

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences

Significance Epidemics of microbial infections are a considerable threat to human and animal health. Analysis of 3,615 genome sequences, coupled with virulence studies in animals, permitted us to delineate the nature and timing of molecular events that contributed to an ongoing global human epidemic of infections caused by group A Streptococcus, the “flesh-eating” pathogen. We clarified decades-long uncertainty about the timing and sequence of genomic alterations that underpinned the global epidemic. Analyses of this type are crucial for developing better strategies to predict and monitor strain emergence and epidemics, formulate effective protective public health maneuvers, and develop or modify vaccines. We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD+-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.

Laboratory Characterization of Methicillin-Resistant Staphylococcus aureus in Canadian Hospitals: Results of 5 Years of National Surveillance, 1995–1999

Two thousand seven hundred eighty single-patient, methicillin-resistant Staphylococcus aureus (MRSA) isolates collected between January 1995 and December 1999 at 17 tertiary care hospital sites across Canada were characterized by phenotypic and genotypic techniques. Six clonal types, as defined by pulsed-field gel electrophoresis, comprised 87% of all isolates and were labeled Canadian (C) MRSA-1 through -6. CMRSA-1 was the most prevalent clonal type, representing 45% of all MRSA. CMRSA-2 was indistinguishable from the New York clone and was more likely to be associated with community acquisition. CMRSA-3 was more likely to cause an infection, compared with the other CMRSA types. CMRSA-4 was indistinguishable from epidemic (E) MRSA-16 from the United Kingdom. Both CMRSA-5 and -6 occurred primarily in single-site, multiyear outbreaks. This study confirms that the epidemiology of MRSA in Canada is evolving, but most isolates at this time appear to belong to one of a small number of epidemic clones.

A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults ≥65 years of age

We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.

Distribution of Antiseptic Resistance Genes qacA, qacB, and smr in Methicillin-Resistant Staphylococcus aureus Isolated in Toronto, Canada, from 2005 to 2009

ABSTRACT Decreased susceptibility to chlorhexidine gluconate (CHDN) in methicillin-resistant Staphylococcus aureus (MRSA) is associated with the qacA, qacB, and smr genes, encoding efflux pumps. A total of 334 MRSA isolates were collected from two Canadian intensive care units between 2005 and 2009. We identified the qacAB genes in 7 strains (2%; 2 qacA genes and 5 qacB genes) and the smr gene in 23 (7%) strains. CHDN minimal bactericidal concentrations were slightly higher for strains harboring smr genes.

Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age.

BACKGROUNDnThe currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng).nnnMETHODSnIn this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng.nnnRESULTSnA total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients.nnnCONCLUSIONSnA short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

The individual, environmental, and organizational factors that influence nurses' use of facial protection to prevent occupational transmission of communicable respiratory illness in acute care hospitals

n n Backgroundn Communicable respiratory illness is an important cause of morbidity among nurses. One of the key reasons for occupational transmission of this illness is the failure to implement appropriate barrier precautions, particularly facial protection. The objectives of this study were to describe the factors that influence nurses decisions to use facial protection and to determine their relative importance in predicting compliance.n n n Methodsn This cross-sectional survey was conducted in 9 units of 2 urban hospitals in which nursing staff regularly use facial protection.n n n Resultsn A total of 400 self-administered questionnaires were provided to nurses, and 177 were returned (44% response rate). Less than half of respondents reported compliance with the recommended use of facial protection (eye/face protection, respirators, and surgical masks) to prevent occupational transmission of communicable respiratory disease. Multivariate analysis showed 5 factors to be key predictors of nurses compliance with the recommended use of facial protection. These factors include full-time work status, greater than 5 years tenure as a nurse, at least monthly use of facial protection, a belief that media coverage of infectious diseases impacts risk perception and work practices, and organizational support for health and safety.n n n Conclusionn Strategies and interventions based on these findings should result in enhanced compliance with facial protection and, ultimately, a reduction in occupational transmission of communicable respiratory illness.n n

Interim estimates of 2014/15 influenza vaccine effectiveness in preventing laboratory-confirmed influenza-related hospitalisation from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network, January 2015.

The 2014/15 influenza season in Canada has been characterised to date by early and intense activity dominated by influenza A(H3N2). A total of 99.0% (593/599) hospitalisations for laboratory-confirmed influenza with a known influenza virus type enrolled in sentinel hospitals of the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network were due to influenza A. Of the 216 with a known subtype, influenza A(H3N2) accounted for 99.1% (n=214). Interim unmatched vaccine effectiveness (VE) estimates adjusted for age and presence of one or more medical comorbidities were determined by test-negative case-control design to be ?16.8% (90% confidence interval (CI): ?48.9 to 8.3) overall and ?22.0% (90% CI: ?66.5 to 10.7) for laboratory-confirmed influenza A(H3N2). Among adults?aged under?65 years, the overall VE was 10.8% (90% CI: ?50.2 to 47.0) while in adults?aged 65 years or older, the overall VE was ?25.4% (90% CI: ?65.0 to 4.6). .