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The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared

ImportanceTrends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described.ObjectiveTo describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic.Design, Setting, and ParticipantsActive prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)–participating hospital.ExposuresCOVID-19 waves, COVID-19 vaccination status, and age group.Main Outcomes and MeasuresThe CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death.ResultsAmong 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively).Conclusions and RelevanceThe findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Background Antimicrobial resistance is a growing threat to the world’s ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada. Methods In this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014–2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd). Results Between 2009 and 2016, 16–18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ≥1 year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p = 0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p Conclusions This study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

Objectives:The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use.Methods:Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%.Results:In each survey, 28−47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%−37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%−41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%−40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60).Conclusions:The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.

Between 18-Dec-2017 and 27-Jun-2018, a mumps outbreak occurred in two Canadian Indigenous communities. An outbreak dose of mumps-containing vaccine was offered as part of control measures. We conducted a cohort study and survival analysis to describe the outbreak and evaluate the outbreak dose, extracting immunization information on all community members (n=3,135) from immunization records. There were 70 mumps cases; 56% had received two pre-outbreak vaccine doses. Those who received a pre-outbreak dose more distantly had higher rates of mumps compared to those with more recent doses (adjusted hazard ratio = 3.4 (95%CI: 0.7–20.6) for receipt >20 years before vs. receipt ≤3 years). During the outbreak, 33% (1,010/3,080) of eligible individuals received an outbreak dose. The adjusted hazard ratio for no outbreak dose receipt was 2.7 (95%CI: 1.0–10.1). Our results suggest that an outbreak dose of mumps-containing vaccine may be an effective public health intervention, but further study is warranted.

BACKGROUND: Information on the epidemiology of patients in hospital with laboratory-confirmed coronavirus disease 2019 (COVID-19) in Canadian acute care hospitals is needed to inform infection prevention and control strategies and public health measures. The aim of this surveillance was to describe the epidemiology of patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals between Mar. 1 and Aug. 31, 2020. METHODS: Through prospective surveillance, we identified adult and pediatric patients in hospital with laboratory-confirmed COVID-19 using a standard definition between Mar. 1 and Aug. 31, 2020, through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 78 hospitals. Patient demographic and clinical characteristics and data on treatment, interventions and outcomes were reviewed and described. RESULTS: As of Aug. 31, 2020, the CNISP had received data for 1906 patients in hospital with COVID-19 in 49 sentinel hospitals in 9 provinces. The majority of patients in hospital with COVID-19 were older (median age 71 yr) and had underlying medical conditions (85.8%). Few children with COVID-19 were admitted to a participating hospital (n = 37, 1.9%). Acquisition of COVID-19 in hospitals was infrequent (6.4% of all cases). A total of 32.8% of patients were admitted from a long-term care facility or retirement home. Health care workers constituted 10.6% of adult patients aged 18-65 years in hospital with COVID-19. Thirty-day attributable mortality was 16.2%. Hospital admission rates peaked in mid-April and were highest in Ontario and Quebec. INTERPRETATION: Surveillance findings indicate that a high proportion of Canadian patients in hospital with COVID-19 during the first 6 months of the pandemic were older adults with underlying medical conditions. Active surveillance of patients in hospital with COVID-19 is critical to enhancing our knowledge of the epidemiology of COVID-19 and to identifying populations at risk for severe outcomes, which will help guide Canada's response in the coming months.

Background: Nosocomial central-line–associated bloodstream infections (CLABSIs) are an important cause of morbidity and mortality in hospitalized patients. CLABSI surveillance establishes rates for internal and external comparison, identifies risk factors, and allows assessment of interventions. Objectives: To determine the frequency of CLABSIs among adult patients admitted to intensive care units (ICUs) in CNISP hospitals and evaluate trends over time. Methods: CNISP is a collaborative effort of the Canadian Hospital Epidemiology Committee, the Association of Medical Microbiologists and Infectious Disease Canada and the Public Health Agency of Canada. Since 1995, CNISP has conducted hospital-based sentinel surveillance of healthcare-associated infections. Overall, 55 CNISP hospitals participated in ≥1 year of CLABSI surveillance. Adult ICUs are categorized as mixed ICUs or cardiovascular (CV) surgery ICUs. Data were collected using standardized definitions and collection forms. Line-day denominators for each participating ICU were collected. Negative-binomial regression was used to test for linear trends, with robust standard errors to account for clustering by hospital. We used the Fisher exact test to compare binary variables. Results: Each year, 28–42 adult ICUs participated in surveillance (27–37 mixed, 6–8 CV surgery). In both mixed ICUs and CV-ICUs, rates remained relatively stable between 2011 and 2018 (Fig. 1). In mixed ICUs, CLABSI rates were 1.0 per 1,000 line days in 2011, and 1.0 per 1,000 line days in 2018 (test for linear trend, P = .66). In CV-ICUs, CLABSI rates were 1.1 per 1,000 line days in 2011 and 0.8 per 1,000 line days in 2018 (P = .19). Case age and gender distributions were consistent across the surveillance period. The 30-day all-cause mortality rate was 29% in 2011 and in 2018 (annual range, 29%–35%). Between 2011 and 2018, the percentage of isolated microorganisms that were coagulase-negative staphylococci (CONS) decreased from 31% to 18% (P = .004). The percentage of other gram-positive organisms increased from 32% to 37% (P = .34); Bacillus increased from 0% to 4% of isolates and methicillin-susceptible Staphylococcus aureus from 2% to 6%). The gram-negative organisms increased from 21% to 27% (P = .19). Yeast represented 16% in 2011 and 18% in 2018; however, the percentage of yeast that were Candida albicans decreased over time (58% of yeast in 2011 and 30% in 2018; P = .04). Between 2011 and 2018, the most commonly identified species of microorganism in each year were CONS (18% in 2018) and Enterococcus spp (18% in 2018). Conclusions: Ongoing CLABSI surveillance has shown stable rates of CLABSI in adult ICUs from 2011 to 2018. The causative microorganisms have changed, with CONS decreasing from 31% to 18%.Funding: CNISP is funded by the Public Health Agency of Canada.Disclosures: Allison McGeer reports funds to her for studies, for which she is the principal investigator, from Pfizer and Merck, as well as consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

BACKGROUND: Health care–associated infections are a common cause of patient morbidity and mortality. We sought to describe the trends in these infections in acute care hospitals, using data from 3 national point-prevalence surveys. METHODS: The Canadian Nosocomial Infection Surveillance Program (CNISP) conducted descriptive point-prevalence surveys to assess the burden of health care–associated infections on a single day in February of 2002, 2009 and 2017. Surveyed infections included urinary tract infection, pneumonia, Clostridioides difficile infection, infection at surgical sites and bloodstream infections. We compared the prevalence of infection across the survey years and considered the contribution of antimicrobial-resistant organisms as a cause of these infections. RESULTS: We surveyed 28 of 33 (response rate 84.8%) CNISP hospitals (6747 patients) in 2002, 39 of 55 (response rate 71.0%) hospitals (8902 patients) in 2009 and 47 of 66 (response rate 71.2%) hospitals (9929 patients) in 2017. The prevalence of patients with at least 1 health care–associated infection increased from 9.9% in 2002 (95% confidence interval [CI] 8.4%–11.5%) to 11.3% in 2009 (95% CI 9.4%–13.5%), and then declined to 7.9% in 2017 (95% CI 6.8%–9.0%). In 2017, device-associated infections accounted for 35.6% of all health care–associated infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 3.9% of all organisms identified from 2002 to 2017; other antibiotic-resistant organisms were uncommon causes of infection for all survey years. INTERPRETATION: In CNISP hospitals, there was a decline in the prevalence of health care–associated infection in 2017 compared with previous surveys. However, strategies to prevent infections associated with medical devices should be developed. Apart from MRSA, few infections were caused by antibiotic-resistant organisms.

Background Pneumococcal disease burden is difficult to quantify due to limited data regarding non-bacteremic disease. We assessed serotype-specific differences in pneumococcal disease presentations in adults in Toronto, Canada. Methods From 2003 to 2011, population-based surveillance for invasive pneumococcal disease was conducted and respiratory pneumococcal isolates collected in Metropolitan Toronto/Peel Region, Canada. Episodes of care were classified into disease categories. Results Of 3105 eligible cases of IPD, 2060 cases were bacteremic pneumonia, and 1045 bacteremia without pneumonia. Of 2751 eligible respiratory cases, 1542 (56.0%) were non-bacteremic pneumonia (NBPP), 467 (17.0%) were other acute respiratory infection (oARI), and 742 (27.0%) were isolates representing colonization. Serotypes 3 (11.3%), 19A (8.4%) and 22F (6.2%) were the most common; serotypes 1,5, and 8 were rare. Serotypes 4, 14, 7F, 9V, 12F, 14, 19A and 6C were over-represented in bacteremic disease, and serotypes 3, 6A, 11A, 19F, 23A, 23F, 35B, 35F were more common in NBPP. The proportion of cases due to PCV7 serotypes declined from 48.7% to 8.7% in bacteremic pneumonia, from 35.3% to 10.9% in NBPP, from 34.2% to 7.5% in oARI, and from 38.7% to 12.2% in colonizing isolates. In 2010–2011, PCV13 serotypes accounted for 62.6% of isolates associated with bacteremic pneumonia, 42.0% of bacteremia without pneumonia, 41.1% of NBPP, 25.7% of oARI, and 32.9% of colonizing isolates. Conclusions Serotype distributions differ significantly in different presentations of pneumococcal disease. Herd protection due to PCV7 has changed serotype distribution, but PCV13 serotypes remain important in all categories of disease.

Background: The association between antimicrobial use (AMU) and emergence of antimicrobial resistance is well documented. The Canadian Nosocomial Infection Surveillance Program (CNISP) has conducted sentinel surveillance of AMU at participating Canadian hospitals since 2009 resulting in the largest pan-Canadian hospital database of dispensed antimicrobials. Objectives: Describe interhospital variability of AMU across Canada. Methods: Hospitals submit annual AMU data based on patient days (PD). Antimicrobials were measured in defined daily doses (DDD) for adults using the WHO Anatomical Therapeutic Chemical (ATC) system. The AMU data among pediatric patients have been available since 2017 using days of therapy (DOT). Surveillance includes systemic antibacterial agents (J01 ATC codes), oral metronidazole, and oral vancomycin. AMU was assessed using quintiles, interquartile ranges (IQR), and relative IQRs (upper- and lower-quartile values divided by the median). Results: Between 2009 and 2018, 20–26 hospitals participated in adult surveillance each year (35 teaching hospitals and 3 nonteaching hospitals participated in ≥1 year). Over this period, overall AMU decreased by 13% at participating adult hospitals from 645 to 560 DDD per 1,000 PD. AMU varied substantially between hospitals, but this variability decreased over time (Fig. 1). In 2009, the IQRs for overall AMU spanned 309 DDD per 1,000 PD, and in 2018 it spanned only 103 DDD per 1,000 PD. This decrease in variability was due to large decreases in use among hospitals with high use in 2009–2010. Among hospitals in the highest use quintile in 2009–2010, AMU decreased, on average, 44 DDD per 1,000 PD each year. Among hospitals in the lowest use quintile in 2009–2010, AMU increased, on average, 6 DDD per 1,000 PD each year. In 2018, antibiotics with the largest absolute IQR variability were cefazolin (61–113 DDD per 1,000 PD), piperacillin-tazobactam (32–64 DDD per 1,000 PD), and vancomycin (24–49 DDD per 1,000 PD). Among antibiotics with ≥1 DDD per 1,000 PD, antibiotics with the largest relative IQR variability were tobramycin (0.3–6 DDD per 1,000 PD), cefadroxil (0.08–9 DDD per 1,000 PD), and linezolid (0.2–3 DDD per 1,000 PD). In 2018, the IQR for overall pediatric AMU (n = 7 teaching hospitals) was 426–581 DOT per 1,000 PD. Antibiotics with the largest IQRs were vancomycin (0.6–58 DOT per 1,000 PD), cefazolin (33–88 DOT per 1,000 PD), and tobramycin (3–57 DOT per 1,000 PD). Among antibiotics with ≥1 DOT per 1,000 PD in 2018, antibiotics with the largest relative IQRs were tobramycin (3–57 DOT per 1,000 PD), cefuroxime (1–6 DOT per 1,000 PD), and amoxicillin (8–42 DOT per 1,000 PD). Conclusions: There is wide variation in overall antibiotic use across hospitals. Variation between AMU at adult hospitals has decreased between 2009 and 2018; in 2018, antibiotics with the largest IQRs were cefazolin and piperacillin-tazobactam. Benchmarking AMU is crucial for informing antimicrobial stewardship efforts.Funding: CNISP is funded by the Public Health Agency of Canada.Disclosures: Allison McGeer reports funds to her institution from Pfizer and Merck for projects for which she is the principal investigator. She also reports consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

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.

BACKGROUND: Survey data suggest that Canadian intensivists administer corticosteroids to critically ill patients primarily in response to airway obstruction, perceived risk for adrenal insufficiency and hemodynamic instability.OBJECTIVE: To describe variables independently associated with systemic corticosteroid therapy during an influenza outbreak.METHODS: The present analysis was retrospective cohort study involving critically ill patients with influenza in two Canadian cities. Hospital records were reviewed for critically ill patients treated in the intensive care units (ICUs) of eight hospitals in Canada during the 2008 to 2009 and 2009 to 2010 influenza outbreaks. Abstracted data included demographic information, symptoms at disease onset, chronic comorbidities and baseline illness severity scores. Corticosteroid use data were extracted for every ICU day and expressed as hydrocortisone dose equivalent in mg. Multivariable regression models were constructed to identify variables independently associated with corticosteroid therapy in the ICU.RESULTS: The study cohort included 90 patients with a mean (± SD) age of 55.0±17.3 years and Acute Physiology and Chronic Health Evaluation II score of 19.8±8.3. Patients in 2009 to 2010 were younger with more severe lung injury but similar exposure to corticosteroids. Overall, 54% of patients received corticosteroids at a mean daily dose of 343±330 mg of hydrocortisone for 8.5±4.8 days. Variables independently associated with corticosteroid therapy in the ICU were history of airway obstruction (OR 4.8 [95% CI 1.6 to 14.9]) and hemodynamic instability (OR 4.6 [95% CI 1.2 to 17.8]).CONCLUSION: Observational data revealed that hemodynamic instability and airway obstruction were associated with corticosteroid therapy in the critical care setting, similar to a recent survey of stated practice. Efforts to determine the effects of corticosteroids in the ICU for these specific clinical situations are warranted.

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).

Background Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). Methods We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. Results Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. Conclusions Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.

Publicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults ≥ 65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults ≥ 50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD).Laboratory data from population-based surveillance for IPD conducted at the Toronto Invasive Bacterial Disease Network and from Public Health Ontario Laboratories between January 1, 2008 and December 31, 2010 were analyzed.Between 2008 and 2010 there were 3259 cases of IPD; overall incidence was 7.4/9.3/8.3 per 100,000 in 2008/9/10, respectively. Incidence increased significantly among adults 65+ years during the period; this group had the highest incidence (21.5-25.6/100,000). The second highest incidence in 2008 and 2009 was in infants1 year, whereas in 2010 it was in children 1-4 years. Among children5 years, 68% and 19% of serotypes were covered by PCV13 and PCV10, respectively, between 2008 and 2010. In 2009, 6 cases with the 3 additional PCV10 serotypes were reported in infants compared with 2 in 2010. Among persons eligible for PCV7 (born≥2004), there was a 77% decrease in the rate of IPD due to PCV7 serotypes between 2008 and 2010 and a 60% decrease in PCV7 serotypes among persons not vaccine-eligible (born2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults≥50 years.During Ontario's PCV7 programme, serotype-specific decreases in IPD were observed, suggesting vaccine programme success, including herd immunity. Our results also suggest some early impact among infants from PCV10 introduction. A substantial burden of disease was also observed among older adults.

Background Monitoring the incidence and severity of disease due to varied pneumococcal (Pn) serotypes (STs) over time is important in assessing the benefit of Pn vaccines. We describe changes in adult IPD after the 2010 introduction of routine infant PCV13 in Ontario, Canada (PCV13 is funded only for immunocompromised adults ≥50 years as of 2015). Methods TIBDN has conducted population-based surveillance for IPD in Toronto/Peel, Canada (pop 4.3M) since 1995. Cases are reported to a central office; one isolate/case is serotyped. Demographic and clinical data are collected by chart review and patient/family physician interview. Results Of 6,275 episodes of adult IPD, 5,674 (90%) have STs and 6,007 (96%) detailed clinical data. Incidence of IPD decreased from 14.2/100,000/year in 1995 to 6.0/100,000/year in 2013–2017). One thousand two hundred and three (19%) adults with IPD were 15–44 years, 1,889 (30%) were 45–64 years, 3,182 (51%) ≥65 years. Figures 1 and 2 show rates over time by ST group and age. In multivariable analyses, there was no difference across vaccine ST groups (nonvaccine type (NVT) vs. PPV23 not PCV vs. PCV13) in patient age, proportion with ICU admission, requirement for mechanical ventilation (MV), death, length of stay (LOS) or diagnosis of meningitis, except that patients with NVT isolates were more likely to require ICU admission (OR 1.5, 95% CI 1.2,2.0), and to have meningitis (OR 1.9, 95% CI 1.1,3.3). Case fatality declined from 25% (480/1,949) 1995–2001 to 19% (148/763) in 2012–2017 (multivariable OR/year 0.98 95% CI 0.97,0.99); requirements for ICU admission (26–31%; OR/year 1.02, 95% CI 1.01,1.03) and MV (OR/year 18–22%; 1.02, 95% CI 1.01–1.03) increased, LOS did not change. From 2013 to 2017, the distribution of vaccine group STs has not changed: 37% PCV13 (383/1,031); 20% PCV20not13 (205); 9% PPV23not 20 (94), 34% NVT (349). NVT strains include over 23 ST, most commonly 23A (72, 21%), 15A (46, 13%), 35B (37,11%), 6C (36, 10%), 23B (20, 8%). Conclusion In our population, with infant but no routine adult PCV13, the incidence of adult IPD appears to have stabilized, with PCV13 ST strains contributing 37% of IPD. Case fatality has decreased; ICU admission increased. Adult vaccination may be required to further reduce PCV13 ST infections. Figure 1: IPD incidence, adults 15–65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010. Figure 1. IPD incidence, adults ≥65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010. Disclosures A. McGeer, Pfizer: Grant Investigator and Scientific Advisor, Research grant and Research support; Merck: Scientific Advisor, Research support; GlaxoSmithKline: Grant Investigator and Scientific Advisor, Research support.

Background Several studies have documented factors predictive of antimicrobial resistance (AMR) in invasive pneumococcal disease(IPD). However, the implementation of routine pediatric PCV programs, antimicrobial stewardship, and increasing immunocompromised in populating might be expected to change such factors. We report on predictive factors for AMR in IPD from 2012 to 2017. Methods TIBDN performs population-based surveillance for IPD in Toronto/Peel (pop 4.5M). IPD cases are reported to a central office and one isolate/case is serotyped and has antimicrobial susceptibility testing performed by broth microdilution to CLSI standards. Results 2459 cases of IPD were identified from January 2012 to December 2017. Overall rates of resistance to penicillin, macrolides, fluoroquinolones, and TMP-SMX were relatively stable over the course were stable over the study. Risk factors for infection with resistant to penicillin at meningitis breakpoints as opposed to penicillin- susceptible pneumococci were current residence at nursing home (odds ratio [OR], 2.30; P < 0.001), immune compromised status (OR, 1.41; P = 0.012), HIV infection (OR 2.13, P = 0.016), history of receiving PPV23 vaccine (OR 1.38; P = 0.007). Infection with TMP-SMX-resistant pneumococci was associated with HIV infection (OR, 3.2; P = 0.001) and current residence in a nursing home (OR 2.4, P = 0.002). Infection with macrolide-resistant isolates was associated with any use of macrolide 3 months prior to infection (OR, 3.24; P < 0.001), or macrolide treatment failure of the current episode (OR, 6.64; P = 0.003). Infection with levofloxacin-resistant pneumococci was associated with current residence in a nursing home (OR, 13.7; P < .001), and fluorquinolone treatment failure of the current episode (OR 49.4, P = 0.0034). Conclusion Previous same class antibiotic exposure remains a major predictive factor for macrolide resistance. History of treatment failure is a predictive factor for macrolide and fluoroquinolone failure. HIV infection and immune compromise are risk factors for IPD infection with penicillin resistant pneumococci. Hospital acquisition of infection is no longer a risk factor for fluoroquinolone resistance. Disclosures All authors: No reported disclosures.

Background In Ontario a publicly funded PCV7 infant program (3 + 1 schedule), was introduced in 1/2005, PCV10 in 10/2009 and PCV13 in 11/2010 (2 + 1 schedule with catch-up to 35m). TIBDN performs population-based surveillance for invasive pneumococcal disease (IPD) in Toronto/Peel to evaluate program impact. Methods IPD cases are reported to a central office and one isolate/case is serotyped. Demographic/ clinical data are collected by chart review and patient/physician interview. Results From 1/1995–5/2017, 9727 IPD cases have been identified. Among 910 IPD cases since 2015, 109 (12%) were aged

In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13).From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada.6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F.While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults.

Between 2008 and 2011, 6,895 Streptococcus pneumoniae isolates were submitted to the Canadian Bacterial Surveillance Network and underwent in vitro susceptibility testing. Fifteen percent of S. pneumoniae isolates were collected from pediatric patients (0–15 years old), 48.6 % of isolates were collected from adults between 16 and 64 years of age, and 36.1 % from adults aged ≥65 years; age data were not available for 11 patients. Forty-five percent of S. pneumoniae isolates were recovered from sterile specimens, and 55 % of isolates were from nonsterile specimens. Overall, 0.4 % of isolates were resistant to penicillin, 0.4 % to ceftriaxone, 3 % to amoxicillin, 25 % to erythromycin, and 13 % to trimethoprim/sulfamethoxazole; 6.6 % of isolates were multidrug resistant (MDR). Among MDR isolates, resistance rates exceeded 95 % for erythromycin, tetracycline, and trimethoprim/sulfamethoxazole. The MIC90 of cethromycin, ceftaroline, and ceftobiprole against MDR isolates were 0.12, 0.25, and 1 mg/L, respectively. Ceftaroline, the active form of the prodrug ceftaroline fosamil, exhibited potent in vitro activity against the tested S. pneumoniae including all 456 multidrug-resistant strains. No ceftaroline-resistant isolates were identified.