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Background Understanding the burden of influenza is necessary to optimize recommendations for influenza vaccination. We describe the epidemiology of severe influenza in 50- to 64-year-old residents of metropolitan Toronto and Peel region, Canada, over 7 influenza seasons. Methods Prospective population-based surveillance for hospitalization associated with laboratory-confirmed influenza was conducted from September 2010 to August 2017. Conditions increasing risk of influenza complications were as defined by Canada's National Advisory Committee on Immunization. Age-specific prevalence of medical conditions was estimated using Ontario health administrative data. Population rates were estimated using Statistics Canada data. Results Over 7 seasons, 1228 hospitalizations occurred in patients aged 50–64 years: 40% due to A(H3N2), 30% A(H1N1), and 22% influenza B. The average annual hospitalization rate was 15.6, 20.9, and 33.2 per 100 000 in patients aged 50–54, 55–59, and 60–64 years, respectively; average annual mortality was 0.9/100 000. Overall, 33% of patients had received current season influenza vaccine; 963 (86%) had ≥1 underlying condition increasing influenza complication risk. The most common underlying medical conditions were chronic lung disease (38%) and diabetes mellitus (31%); 25% of patients were immunocompromised. The average annual hospitalization rate was 6.1/100 000 in those without and 41/100 000 in those with any underlying condition, and highest in those with renal disease or immunocompromise (138 and 281 per 100 000, respectively). The case fatality rate in hospitalized patients was 4.4%; median length of stay was 4 days (interquartile range, 2–8 days). Conclusions The burden of severe influenza in 50- to 64-year-olds remains significant despite our universal publicly funded vaccination program. These data may assist in improving estimates of the cost-effectiveness of new strategies to reduce this burden. [ABSTRACT FROM AUTHOR]

In multivariable analysis of associations between initial antibiotic therapy and clinical outcomes in 5005 patients with microbiologically confirmed Streptococcus pneumoniae infections,"discordant" empiric antibiotic therapy was not associated with 30-day mortality rate (hazard ratio, 0.94; 95% confidence interval, .67-1.32). [ABSTRACT FROM AUTHOR]

Background. We conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada. Methods. Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset. Results. Data were available for 512 of 541 eligible patients. There were 185 children (!15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15-98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06-0.80; Pp.03). There was no apparent impact of antiviral therapy on length of stay in survivors. Conclusions. There is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality. [ABSTRACT FROM AUTHOR]

Background In Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population. Methods TIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada. Results Since 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P =.03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3. Conclusion A significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background. Background Invasive Group A streptococcal (iGAS) infections remain a substantial source of morbidity and mortality. We explore the clinical and molecular epidemiology of iGAS infections in Toronto, Ontario, Canada over a 26-year period. Methods The Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for iGAS infections in metropolitan Toronto and Peel regions since 1992. Participating microbiology laboratories report and submit sterile site specimens for central processing. M typing was performed on iGAS isolates until September 2006; thereafter emm typing was performed. Clinical information was collected by chart review using standardized collection forms. Results Over the 26-year period there were 2819 iGAS infections, representing an average incidence of 2.85 per 100,000 residents with a nadir of 1.65 in 1993 and a peak of 4.52 in 2014. Nosocomial infections occurred in 8.9% (251/2,819). There was substantial variation in annual incidence rates over the study period with increases from 1992 until 2002 and then 2004 until 2014 (analysis for trend, P < 0.001). Skin and soft-tissue infections were the most common clinical presentation, accounting for 33.2% (936/2,819), followed by bacteremia without a focus in 15.4% (435/2,819). Necrotizing fasciitis was observed in 7.4% (208/2,819) and criteria for toxic shock syndrome were met in 17.6% (497/2,819). Overall case fatality within 30 days of hospitalization was 15.3% (95% confidence interval 14.0 to 16.6) and did not change over time. M serotype distribution varied yearly with the most common type being M1 at 22.2% (626/2,189) followed by M12 at 8.2% (230/2,189), then M89 at 5.8% (163/2,189). Antibiotic susceptibility was available from 1998 onwards with overall clindamycin susceptibility at 92.3% (1,957/2,121) and erythromycin susceptibility at 87.9% (1864/2,121). Conclusion The incidence of iGAS in Toronto, Ontario has varied over time, with no recent increase apparent. Similar to worldwide observations, M1 serotype was the most commonly isolated; most common serotypes demonstrated cyclical variation. Case fatality rates have remained relatively constant making the development of a vaccine imperative. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively. Methods We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide. Results Genome analysis showed that highly clonal emm74 strains, genetically different from emm74 organisms previously circulating in Canada, were responsible for a country-wide epidemic of >160 invasive disease cases. The emerging clone belonged to multilocus sequence typing ST120. The analysis also revealed dissemination patterns of emm74 subclonal lineages across Canadian provinces. Clinical data analysis indicated that the emm74 epidemic disproportionally affected middle-aged or older male individuals. Homelessness, alcohol abuse, and intravenous drug usage were significantly associated with invasive emm74 infections. Conclusions In a period of 20 months, an emm74 GAS clone emerged and rapidly spread across several Canadian provinces located more than 4500 km apart, causing invasive infections primarily among disadvantaged persons. [ABSTRACT FROM AUTHOR]