Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends 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. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active 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. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The 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. Results: Among 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 Relevance: The 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.

Trends in Clostridioides difficile infection rates in Canadian hospitals during the coronavirus disease 2019 (COVID-19) pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Antimicrobial use in Canadian acute-care hospitals: Findings from three national point-prevalence surveys between 2002 and 2017.

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.

Effectiveness of an outbreak dose of mumps-containing vaccine in two First Nations communities in Northern Ontario, Canada.

Between 18 Dec 2017 and 27 June 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 vaccination information on all community members (n = 3,135) from vaccination 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.

Overview of Canada's Antimicrobial Resistance Network (AMRNet): A data-driven One Health approach to antimicrobial resistance surveillance.

The Antimicrobial Resistance Network (AMRNet) is a laboratory-based antimicrobial resistance (AMR) surveillance system under development at the Public Health Agency of Canada's (PHAC's) National Microbiology Laboratory. The AMRNet surveillance system captures information on antimicrobial susceptibility testing from clinical and veterinary laboratories including both public and private facilities. In the future, the AMRNet system will also capture relevant data from existing PHAC surveillance systems for AMR including the Canadian Integrated Program for Antimicrobial Resistance Surveillance, the Canadian Nosocomial Infection Surveillance Program and the Enhanced Surveillance of Antimicrobial-Resistant Gonorrhea program, and contribute to the Canadian Antimicrobial Resistance Surveillance System. AMRNet's integrated "One Health" approach will allow health professionals and researchers to take a multi-dimensional perspective of AMR in both human and animal health in Canada and will make Canada a leader in AMR surveillance. AMRNet is a collaboration between PHAC, provincial and territorial public health organizations as well as clinical and veterinary laboratories across the country. As part of a phased rollout, AMRNet is now collecting human clinical data from three provinces, from both inpatients and outpatients. Ultimately, AMRNet aims to capture all antimicrobial susceptibility testing results from all bacterial and fungal pathogens across Canada. This article describes the AMRNet surveillance system, including program objectives, system structure and the data collected. The integration of human and animal data in AMRNet will inform One Health responses to AMR issues. The capacity to collect and to disseminate data to stakeholders in real time is a critical step to addressing emerging AMR issues in Canada.

Patients in hospital with laboratory-confirmed COVID-19 in a network of Canadian acute care hospitals, Mar. 1 to Aug. 31, 2020: a descriptive analysis.

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.

Prevalence of Candida auris in Canadian acute care hospitals among at-risk patients, 2018.

To identify the prevalence of C. auris in Canadian patients who are potentially at risk for colonization, we screened 488 patients who were either hospitalized abroad, had a carbapenemase-producing organism (CPO), or were in units with high antifungal use. Two patients were colonized with C. auris; both had received healthcare in India and had a CPO. Among 35 patients who had recently received healthcare in the Indian subcontinent and were CPO colonized or infected, the prevalence of C. auris was 5.7%.

Antimicrobial use among adult inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program: 2009 to 2016.

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 < 0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p = 0.002) and 26% (p = 0.002) respectively. Ceftriaxone (85% increase, p = 0.0008) and oral amoxicillin-clavulanate (140% increase, p < 0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use. 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.

Trends in health care-associated infections in acute care hospitals in Canada: an analysis of repeated point-prevalence surveys.

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.

Factors Associated With 30-Day Mortality Rate in Respiratory Infections Caused by Streptococcus pneumoniae.

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).

Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs.

BACKGROUND: In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. METHODS: From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. RESULTS: Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. CONCLUSIONS: Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established.

Association of serotype with respiratory presentations of pneumococcal infection, Ontario, Canada, 2003-2011.

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.

Corticosteroid therapy in critical illness due to seasonal and pandemic influenza.

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.

Human endogenous retrovirus-K(II) envelope induction protects neurons during HIV/AIDS.

Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and physiological circumstances. HERV-K has been implicated in the pathogenesis of several diseases although the functional consequences of its expression remain unknown. Human immunodeficiency virus (HIV) infection causes neuroinflammation with neuronal damage and death. Herein, we investigated HERV-K(II)/(HML-2) envelope (Env) expression and its actions in the brain during HIV/AIDS. HERV-K(II) Env expression was assessed in healthy brain tissues, autopsied HIV HIV- infected (HIV+) and uninfected (HIV-) brains and in neural cell cultures by real time RT-PCR, massively parallel (deep) sequencing, immunoblotting and immunohistochemistry. Neuronal and neural stem cells expressing HERV-K(II) Env were analyzed in assays of host responses including cellular viability, immune responses and neurobehavioral outcomes. Deep sequencing of human brain transcriptomes disclosed that RNA sequences encoded by HERV-K were among the most abundant HERV sequences detected in human brain. Comparison of different cell types revealed that HERV-K(II) env RNA abundance was highest in cultured human neurons but was suppressed by epidermal growth factor exposure. HERV-K(II) Env immunoreactivity was increased in the cerebral cortex from persons with HIV/AIDS, principally localized in neurons. Human neuronal cells transfected with HERV-K(II) Env exhibited increased NGF and BDNF expression. Expression of HERV-K(II) Env in neuronal cells increased cellular viability and prevented neurotoxicity mediated by HIV-1 Vpr. Intracerebral delivery of HERV-K(II) Env expressed by neural stem cells suppressed TNF-α expression and microglial activation while also improving neurobehavioral deficits in vpr/RAG1-/- mice. HERV-K(II) Env was highly expressed in human neurons, especially during HIV/AIDS, but in addition exerted neuroprotective effects. These findings imply that HERV gene products might exert adaptive effects in circumstances of pathophysiological stress, perhaps underlying the conservation of HERVs within the human genome.

In vitro activity of new cephalosporins vs Streptococcus pneumoniae from the Canadian Bacterial Surveillance Network: 2008-2011.

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.

Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.

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.

Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011.

BACKGROUND: 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). METHODS: From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada. RESULTS: 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 children <5 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. CONCLUSIONS: 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.

Have changing pneumococcal vaccination programmes impacted disease in Ontario?

BACKGROUND: 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). METHODS: 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. RESULTS: 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 infants <1 year, whereas in 2010 it was in children 1-4 years. Among children <5 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 (born<2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults≥50 years. CONCLUSIONS: 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.

Biochemical phenotypes to discriminate microbial subpopulations and improve outbreak detection.

BACKGROUND: Clinical microbiology laboratories worldwide constitute an invaluable resource for monitoring emerging threats and the spread of antimicrobial resistance. We studied the growing number of biochemical tests routinely performed on clinical isolates to explore their value as epidemiological markers. METHODOLOGY/PRINCIPAL FINDINGS: Microbiology laboratory results from January 2009 through December 2011 from a 793-bed hospital stored in WHONET were examined. Variables included patient location, collection date, organism, and 47 biochemical and 17 antimicrobial susceptibility test results reported by Vitek 2. To identify biochemical tests that were particularly valuable (stable with repeat testing, but good variability across the species) or problematic (inconsistent results with repeat testing), three types of variance analyses were performed on isolates of K. pneumonia: descriptive analysis of discordant biochemical results in same-day isolates, an average within-patient variance index, and generalized linear mixed model variance component analysis. RESULTS: 4,200 isolates of K. pneumoniae were identified from 2,485 patients, 32% of whom had multiple isolates. The first two variance analyses highlighted SUCT, TyrA, GlyA, and GGT as "nuisance" biochemicals for which discordant within-patient test results impacted a high proportion of patient results, while dTAG had relatively good within-patient stability with good heterogeneity across the species. Variance component analyses confirmed the relative stability of dTAG, and identified additional biochemicals such as PHOS with a large between patient to within patient variance ratio. A reduced subset of biochemicals improved the robustness of strain definition for carbapenem-resistant K. pneumoniae. Surveillance analyses suggest that the reduced biochemical profile could improve the timeliness and specificity of outbreak detection algorithms. CONCLUSIONS: The statistical approaches explored can improve the robust recognition of microbial subpopulations with routinely available biochemical test results, of value in the timely detection of outbreak clones and evolutionarily important genetic events.