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Empirical treatment of urinary tract infections should be based on susceptibility profiles specific to the locale and patient population. Additionally, these susceptibility profiles should account for correlations between resistance to different types of antimicrobials., Empirical treatment of urinary tract infections should be based on susceptibility profiles specific to the locale and patient population. Additionally, these susceptibility profiles should account for correlations between resistance to different types of antimicrobials. We used hierarchical logistic regression models to investigate geographic, temporal, and demographic trends in resistance to six antimicrobials in community-acquired and nosocomial urinary E. coli isolates from three communities in the province of Quebec, Canada, procured between April 2010 and December 2017. A total of 74,986 community-acquired (patient age, ≥18 years) and 4,384 nosocomial isolates (patient age, ≥65 years) were analyzed. In both community-acquired and nosocomial isolates, we found geographic variation in the prevalence of resistance. Male sex (community-acquired hierarchical mean odds ratio [OR], 1.24; 95% credible interval [CI], 1.02 to 1.50; nosocomial hierarchical mean OR, 1.16, 95% CI, 0.92 to 1.41) and recent hospitalization (community-acquired hierarchical mean OR, 1.49; 95% CI, 1.33 to 1.66; nosocomial hierarchical mean OR, 1.31; 95% CI, 0.99 to 1.78) were associated with a higher risk of resistance to most types of antimicrobials. We found distinct seasonal trends in both community-acquired and nosocomial isolates, but only community-acquired isolates showed a consistent annual pattern. Ciprofloxacin resistance increased sharply with patient age. We found clinically relevant differences in antimicrobial resistance in urinary E. coli isolates between locales and patient populations in the province of Quebec. These results could help inform empirical treatment decisions for urinary tract infections. In the future, similar models integrating local, provincial, and national resistance data could be incorporated into decision support systems for clinicians.

We performed a molecular and epidemiologic study of a healthcare-associated rhinovirus outbreak to better understand transmission in neonatal intensive care settings. Sequencing of the 7 outbreak strains revealed 4 distinct clades, indicating multiple sources. A single clade infected 3 patients in adjacent rooms, suggesting horizontal transmission. We observed 1 rhinovirus-associated death.

Recent studies have reported increased levels of Legionella pneumophila (Lp) at points of use compared to levels in primary and secondary components of hot water systems, suggesting possible selection by environmental conditions. In this study, concentrations of Lp in a hospital hot water system were evaluated by profile sampling, collecting successive water samples to determine the prevalence at the faucet (distal) and upstream piping before and after a system intervention to increase temperature. Lp strain diversity was compared between different points of use and different areas of the hot water system (i.e., tap, intermediate piping and main upflow piping). In total, 47 isolates were recovered from 32 positive hot water samples collected from designated taps, showers and recirculation loops; these isolates were subsequently analyzed by sequence-based typing (SBT). Lp levels were comparable between first draw (500 mL) and flushed (2 and 5 min) samples, whereas a decrease was observed in the amount of culturable cells (1 log). Two sequence types (STs) were identified throughout the system. ST378 (sg4/10) was present in 91% of samples, while ST154-like (sg1) was present in 41%; both STs were simultaneously recovered in 34% of samples. Isolated STs displayed comparable tolerance to copper (0.8–5 mg/L) and temperature (55 °C, 1 h) exposure. The ability to replicate within THP1 cells and Acanthamoeba castellanii was similar between the two STs and a comparative environmental outbreak strain. The low Lp diversity and the detection of both Lp sequence types in repeated subsequent samples collected from positive faucets in a hospital wing suggest a minimal impact of the distal conditions on strain selection for the sampled points, as well as a possible adaptation to stressors present in the system, leading to the predominance of a few strains.

Sir,We read with interest a report in the present journal on rotavirus epidemiology 5–6 years after implementation in 2009 of a national immunization program in Finland [1]. Two live vaccines, Rota...

Correction factors have been proposed for traumatic lumbar punctures (LPs) in febrile young infants. However, no studies have assessed their diagnostic utility. We sought to determine the proportion of traumatic LPs safely reclassified as low risk for bacterial meningitis using recently derived white blood cell (WBC) and protein correction factors.We retrospectively analyzed traumatic LPs among all febrile infants ≤60 days old at two tertiary paediatric hospitals from 2006 through 2018. Traumatic LPs were defined as ≥10,000 RBCs/mmThere were 437 traumatic LPs including 357 (82%) with pleocytosis and 4 (0.9%) with bacterial meningitis. Overall, fewer infants were classified as having CSF pleocytosis using 877:1 and 1,000:1 ratios (38% and 43%, respectively), with 100% sensitivity and negative predictive value, and improved specificity (63% for 877:1, 58% for 1,000:1 ratios versus 19% for uncorrected counts). Among infants with pleocytosis, 877:1 and 1,000:1 ratios reclassified 191 (54%) and 171 (48%) as normal with no misclassified bacterial meningitis cases. Ratios of 500:1 and peripheral RBC:WBC misclassified 1 infant that had bacterial meningitis. Corrected CSF protein outperformed uncorrected protein in specificity but did not add diagnostic value following WBC-based correction.Correction ratios of 877:1 and 1,000:1 safely reclassified half of all febrile infants ≤60 days. These corrections should be considered when interpreting CSF results of traumatic LPs.

Background: Rotavirus is a leading cause of viral acute gastroenteritis (AGE) in infants. Neonates hospitalized in neonatal intensive care units (NICUs) are at risk of rotavirus infections with severe outcomes. The administration of rotavirus vaccines is only recommended, in the United States and Canada, upon discharge from the NICU despite rotavirus vaccine being proven safe and effective in these populations, due to risks of live-attenuated vaccine administration in immunocompromised patients and theoretical risks of rotavirus vaccines strains shedding and transmission. We summarized recent evidence regarding rotavirus vaccines administration in the NICU setting and safety of rotavirus vaccines in preterm infants. Methods: We conducted a rapid review of the literature from the past 10 years, searching Medline and Embase, including all study types except reviews, reporting on rotavirus vaccine 1 and rotavirus vaccine 5; NICU setting; shedding or transmission; and/or safety in preterm. One reviewer performed data extraction and quality assessment. Results: In total, 31 articles were analyzed. Vaccine-derived virus shedding following rotavirus vaccination existed for nearly all infants, mostly during the first week after dose 1, with rare transmission described only in the household setting. No case of transmission in the NICU was reported. Adverse events were mild to moderate, occurring in 10%–60% of vaccinated infants. Extreme premature infants or with underlying gastrointestinal failure requiring surgery presented more severe adverse events. Conclusions: Recommendations regarding rotavirus vaccine administration in the NICU should be reassessed in light of the relative safety and absence of transmission of rotavirus vaccine strains in the NICU.Funding: NoneDisclosures: Sicard Mélanie: I reference the use of rotavirus vaccines in the NICU setting, which is not recommended; I discuss possible reassessment of these recommendations.

Background: Neurosurgeries are at high risk of surgical site infections (SSI), a complication associated with increased morbidity, mortality, and cost. Our aim was to measure SSI incidence and risk factors following pediatric neurosurgery at CHU Sainte-Justine, the provincial center for pediatric craniofacial surgery in Québec, Canada. Methods: Retrospective cohort study of all patients with elective neurosurgery performed at CHUSJ between October 2014 and October 2018. Medical records were reviewed to compare demographics, clinical presentations, and outcomes of patients. SSIs occurring within 30 days of a procedure without implant and up to 90 days with implant, were identified. SSI incidence was measured in patient years, and risk factors were assessed using univariate logistic regressions. Results: In total, 379 patients were included with an overall SSI incidence of 3.96 patient years. We found a higher SSI incidence in 2014–2015 compared to 2016–2018 (1.82 vs 4.83 patient years). The median age was 3.90 years, and cases seemed younger than controls (1.45 vs 4.15 years). No difference between groups was found for sex, body mass index, prematurity, and length of hospitalization. The proportion of deep SSIs was greater than superficial SSIs (53.3% vs 46.7%). Cases were more likely to present with a more severe ASA score, previous history of neurosurgery, neurological conditions, and pulmonary conditions than controls: OR, 3.90 (95% CI, 1.36–11.49); OR, 2.59 (95% CI, 0.88–7.40); OR, 2.77 (95% CI, 0.98–8.41), and OR, 3.21 (95% CI, 0.86–9.94), respectively. Among patients with history of neurosurgery, a higher proportion of cases experienced a cerebrospinal fluid leak (28.6% vs 2.2%). Most patients (85.8%) received preoperative prophylactic antibiotic. Of those, 49.3% were considered appropriate based on antibiotic and timing of administration. When antibiotic dosage was also considered, the number of patients who received an appropriate antibiotic therapy decreased radically. Conclusions: Patients with comorbidities, especially neurological and pulmonary conditions, are at higher risk of SSI after neurosurgery. We are currently working on a detailed analysis to explain the increase in SSI incidence after 2016. Finally, prophylactic antibiotic therapy needs to be improved and its impact on SSI rates needs to be monitored.Funding: NoneDisclosures: None

Background: Nosocomial infections cause 4%–56% mortality in newborns. Several epidemiological studies have shown that transmission of opportunistic pathogens from the sink to the patient, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Serratia marcescens are associated with nosocomial infections in neonatal intensive care units (NICUs). In this project, we aimed to develop fast, accurate, and high-throughput multilocus sequence typing assays (HiMLST-Illumina) to detect opportunistic pathogens to assess their distribution in the sink environment of NICUs and their transfer to patients. Methods: Genome sequences of P. aeruginosa (n = 45), S. maltophilia (n = 23) and S. marcescens (n = 34) strains were retrieved from public genome databases to build their pangenomes, using the open-source PGAdb-builder server. The core genome was identified for each opportunistic pathogen and was searched for genes displaying the highest polymorphism. The minimal number of loci to include in a HiMLST-Illumina assay was determined by comparing topology of phylogenetic trees of concatenated loci based on genome similarity, computed as the average nucleotide identity (ANI) score. The primers used for HiMLST-Illumina schemes were designed in silico on a conserved domain and were tested on reference strains of each species. Results: Bioinformatics analyses showed that 3–4 loci (P. aeruginosa was isolated on selective culture media before and 48 hours after disinfection of a sink drain with chlorine. S. marcescens was also isolated from another sink 2 weeks after disinfection. Identification of the isolates was confirmed by HiMLST-Illumina analyses and will be typed to compare with clinical isolates. Conclusions: Initial in silico tests predict a high discriminating power of the HiMLST-Illumina method, suggesting that it would be possible to quickly identify strains of interest in a large number of samples. The power of this method is also in the possibility for molecular typing without a need for cultivation. Preliminary results suggest that sinks are readily colonized by opportunistic pathogens. This HiMLST-Illumina scheme will be applied in a 2-year intensive survey of NICUs in 3 hospitals in Montreal to evaluate the performance of new sink designs in limiting bioaerosol production and transmission of opportunistic pathogens to patients.Funding: NoneDisclosures: None

OBJECTIVECentral-line–associated bloodstream infections (CLABSI) are an important cause of morbidity and mortality in neonates. We aimed to determine whether intra-abdominal pathologies are an independent risk factor for CLABSI.METHODSWe performed a retrospective matched case–control study of infants admitted to the neonatal intensive care units (NICUs) of the Montreal Children’s Hospital (Montreal) and the Royal Alexandra Hospital, Edmonton, Canada. CLABSI cases that occurred between April 2009 and March 2014 were identified through local infection control databases. For each case, up to 3 controls were matched (National Healthcare Safety Network [NHSN] birth weight category, chronological age, and central venous catheter (CVC) dwell time at the time of CLABSI onset). Data were analyzed using conditional logistic regression.RESULTSWe identified 120 cases and 293 controls. According to a matched univariate analysis, the following variables were significant risk factors for CLABSI: active intra-abdominal pathology (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.8–6.4), abdominal surgery in the prior 7 days (OR, 3.5; 95% CI, 1.0–10.9); male sex (OR, 1.7; 95% CI, 1.1–2.6) and ≥3 heel punctures (OR, 4.0; 95% CI, 1.9–8.3). According to a multivariate matched analysis, intra-abdominal pathology (OR, 5.9; 95% CI, 2.5–14.1), and ≥3 heel punctures (OR, 5.4; 95% CI, 2.4–12.2) remained independent risk factors for CLABSI.CONCLUSIONThe presence of an active intra-abdominal pathology increased the risk of CLABSI by almost 6-fold. Similar to CLABSI in oncology patients, a subgroup of CLABSI with mucosal barrier injury should be considered for infants in the NICU with active intra-abdominal pathology.Infect Control Hosp Epidemiol 2016;1446–1452

BACKGROUNDPolymerase chain reaction (PCR) assays based on the detection of the toxin B gene are replacing enzyme-linked immunosorbent assay (ELISA)–based toxin production detection or cell cytotoxicity assay in most laboratories.OBJECTIVETo determine the proportion of pediatric patients diagnosed withClostridium difficile infection by PCR who would have also been diagnosed by ELISA and to compare the clinical characteristics of PCR+/ELISA+ vs PCR+/ELISA− patients.METHODSUsing the microbiology laboratory information system, stool samples positive for C. difficile by PCR between October 2010 and July 2014 were identified. Using frozen stool specimens, an ELISA for toxin A and B was performed. A retrospective medical chart review was conducted to obtain demographic and clinical data. Duplicate samples were excluded.RESULTSA total of 136 PCR-positive samples underwent ELISA testing: 54 (40%) were positive for toxin A or B. The mean (SD) age of the entire cohort was 8.5 (6.2) years. There was no difference in age, gender, clinical manifestation, previous medical problems, and management between patients positive or negative by ELISA. However, patients positive by ELISA were more likely to have had a recent exposure to antibiotics (67.9% vs 50%; crude odds ratio, 2.1 [95% CI, 1.03–4.28]).CONCLUSIONIn our pediatric population, 60% of patients with C. difficile diagnosed by PCR had no toxin detectable by ELISA. ELISA-negative patients were less likely to have received an antibiotic recently compared with ELISA-positive patients. These results highlight the need to standardize laboratory criteria for the diagnosis of C. difficile infections in children.Infect Control Hosp Epidemiol 2016;37:1087–1093

OBJECTIVE:Well-appearing febrile infants with viral illnesses cannot be distinguished from those with occult life-threatening infections. Infants with respiratory viruses are less likely to have serious bacterial infections; however, current risk-stratification criteria predate widespread viral testing and there are limited data to safely inform physician management with this now common diagnostic tool. This study sought to explore the possible impact of respiratory virus testing on clinical decision-making for the management of febrile young infants METHODS:A scenario-based survey was sent to emergency department (ED) and inpatient physicians at all 16 Canadian tertiary pediatric centers. Participants were asked questions regarding management decisions with and without results of respiratory virus testing.RESULTS:Response rate was 78% (n = 330; 190 ED, 140 inpatient). Detection of a respiratory virus reduced admission rates among 3-week-old (83% vs 95%, P < .001) and 5-week-old infants (36% vs 52%, P < .001). Similarly, empirical antibiotic treatment was decreased by detection of a respiratory virus for 3-week-old (65% vs 92%, P < .001) and 5-week-old infants (25% vs 39%, P < .001). Management of 5-week-old infants differed between ED and inpatient physicians, both in the presence and absence of a respiratory virus. There was no consensus among inpatient physicians regarding admission duration for well infants with a detectable respiratory virus and otherwise negative workup.CONCLUSIONS:Respiratory virus testing appears to influence clinical decision-making for febrile infants

Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine. Objective To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50. Methods Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus. Results The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%–69%) for cohort studies and 54% (95% CI: 32%–69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%–26%) for trials, 17% (95% CI: -26%–45%) for cohort studies, and 7% (95% CI: -10%–21%) for case-control studies. Conclusions The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP.

Background The evaluation of fever among infants in the first months of life remains one of the most common problems in pediatric healthcare. Approximately 10% harbor potentially life-threatening infections including bacterial meningitis, frequently necessitating invasive cerebrospinal fluid (CSF) testing by lumbar puncture (LP). LPs are often traumatic leading to uninterpretable results and consequently, broad-spectrum antibiotic exposure and prolonged hospitalization. Several strategies have been proposed to identify low-risk infants with traumatic LPs, including recently-derived correction factors, however studies validating the safety and diagnostic utility of such approaches are lacking. Objectives To evaluate the test characteristics and misclassification rates of recently described ratio-based correction methods for the interpretation of CSF results among young infants with traumatic LPs. Design/Methods We undertook a multicenter cohort study of infants aged ≤60 days with a traumatic LP performed at two urban tertiary Pediatric hospitals from 2006 to 2018. Traumatic LPs were defined as CSF specimens with ≥10,000 RBCs/mm3, and for infants aged ≤28 days and 29-60 days, pleocytosis was defined as ≥20 and ≥10 WBC/mm3, respectively, and abnormal protein ≥1.15 and ≥0.89 g/L, respectively. CSF WBCs and protein were adjusted downward for traumatic LPs using RBC ratio-based correction methods (newly derived 877:1, commonly used 500 and 1000:1, peripheral RBC:WBC ratio, and newly derived 1000 RBCs:0.011g/L protein). Descriptive statistics are presented with sensitivity, specificity, and negative predictive values of unadjusted and adjusted CSF for predicting culture-proven bacterial meningitis. Results Of 4,912 LPs meeting inclusion criteria, 437 (8.9%) were traumatic, among which 4 (0.9%) were positive for bacterial meningitis. Compared to uncorrected CSF WBC counts, both 877 and 1000 correction factors classified fewer infants with pleocytosis (38.0% and 42.6% vs 81.7%). These correction factors both maintained 100% sensitivity and 100% negative predictive value, and performed with greater specificity for bacterial meningitis than the uncorrected WBC count (62.6% and 58.0% vs 18.5%). No infants with bacterial meningitis were misclassified using either 877 or 1000:1 correction factors. CSF 500:1 and peripheral RBC:WBC correction ratios performed with the lowest sensitivity and negative predictive values and both misclassified 1 infant with bacterial meningitis. Corrected CSF protein outperformed uncorrected protein in specificity (66.8% vs 33.9%), but did not add diagnostic value when used in combination with WBC correction ratios. Conclusion Correction of the CSF WBC count substantially reduced the number of infants classified with CSF pleocytosis. The newly-derived 877:1 correction factor performed with the best test characteristics, safely reclassifying nearly half of all infants with a traumatic LP. It may be appropriate to use a correction factor in the evaluation of CSF cell counts in traumatic LPs in order to more effectively risk-stratify febrile young infants, reduce antibiotic exposure and admission duration.

Background Varicella zoster virus (VZV) hospitalizations are an uncommon, severe and costly consequence of VZV. Childhood VZV vaccination leads to decreased VZV rates across all age groups through herd immunity but increases the age of VZV acquisition and the potential risk of severe VZV in non-immune adults. A large proportion (~15%) of young adult immigrants from tropical regions are susceptible to VZV due to different transmission dynamics in their countries of origin and lack of vaccination. We aimed to describe the impact of the childhood VZV program introduced in 2006 in Quebec on VZV hospitalizations in immigrants and nonimmigrants. Methods A population-based cohort of all medically-attended VZV cases in Quebec, Canada (1996–2014) were identified in administrative health databases and linked to immigration data. VZV-attributable hospitalizations included those with primary or secondary ICD-9 or ICD-10 codes for VZV. Overall age-standardized and age-specific rates of hospitalizations were calculated during pre- (1996–98), private (1999–2005) and public vaccination (2006–14) periods and by immigrant status and pregnancy. Relative risk (RRI-NI) and 95% CI for immigrants vs. nonimmigrants were estimated. Results 5873 hospitalizations occurred among 230,052 VZV cases. Hospitalization rates decreased dramatically in the pre to public vaccination period (6.6 to 1.3/100,000 population); however, the proportion of hospitalized varicella cases increased from 1.7% to 3.9% (P < 0.01). Immigrants only accounted for 3.6% of hospitalizations (N = 213) however, the proportion of all hospitalizations among immigrants increased in the pre- vs. public-vaccination periods in those aged 10–19 years (2.9% to 13.7%) and 20–39 years (8.8% to 22.7%). The RR was higher in these age groups in the public vaccination period [RRI-NI 1.96 and RRI-NI 1.67] (Table 1). Adults (>20 years) accounted for 52% (CI: 45–59%) and pregnant women 18% (13–25%) of all hospitalizations among immigrants compared with only 14% (13–15%) and 1.6% (1.3–2.0%) in nonimmigrants, respectively. Conclusion Young adult and pregnant immigrants bore a disproportionate burden of VZV hospitalizations after the introduction of childhood VZV vaccination. Susceptible immigrant adults would benefit from targeted VZV vaccination. Disclosures All authors: No reported disclosures.

OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains unclear. METHODS: We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1–17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences [RD]). RESULTS: Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent [29.4%]) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% [95% confidence interval: 3.3% to 13.1%]) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza. CONCLUSIONS: Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure.

International audience; Serratia marcescens is an environmental bacterium commonly associated with outbreaks in neonatal intensive care units (NICU). Investigation of S. marcescens outbreaks requires efficient recovery and typing of clinical and environmental isolates. In this study, we described how the use of next-generation sequencing applications, such as bacterial whole-genome sequencing (WGS) and bacterial community profiling, could improve S. marcescens outbreak investigation. Phylogenomic links and potential antibiotic resistance genes and plasmids in S. marcescens isolates were investigated using WGS, while bacterial communities and relative abundances of Serratia in environmental samples were assessed using sequencing of bacterial phylogenetic marker genes (16S rRNA and gyrB genes). Typing results obtained using WGS for the ten S. marcescens isolates recovered during a NICU outbreak investigation were highly consistent with those from pulse-field gel electrophoresis (PFGE), the current gold standard typing method for this bacterium. WGS also allowed for the identification of genes associated with antibiotic resistance in all isolates, while no plasmid was detected. Sequencing of the 16S rRNA and gyrB genes both showed higher relative abundances of Serratia in environmental sampling sites that were in close contact with infected babies. Much lower relative abundances of Serratia were observed following disinfection of a room, indicating that the protocol used was efficient. Variations in the bacterial community composition and structure following room disinfection and between sampling sites were also identified through 16S rRNA gene sequencing. Globally, results from this study highlight the potential for next-generation sequencing tools to improve and facilitate outbreak investigation.

Background & objectives Preterm infants are at highest risk for severe rotavirus gastroenteritis. While rotavirus vaccination is recommended for age-eligible, clinically stable preterm infants, controversy exists regarding vaccination of these infants during hospitalization. The objectives of this study were to examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized infants and nosocomial rotavirus transmission in the neonatal intensive care units (NICU) at two urban hospitals. Methods A retrospective, medical chart review of patients receiving RV5 vaccine was conducted to examine clinical histories of vaccine recipients. Average risk differences of gastrointestinal complications were estimated between the three days prior and up to four weeks following RV5 vaccination. A generalized linear regression model was used to examine the association between days since RV5 administration and daily feeding totals, using fixed effects to account for individual-level clustering. Rates of nosocomial rotavirus from active surveillance were compared between pre- and post-NICU-based vaccination periods. Results From July 1, 2011 to March 30, 2013, RV5 vaccination was initiated for 102 NICU patients. No changes in the average risk of gastrointestinal complications or daily feeding among participants overall were detected following RV5 administration. Rates of nosocomial rotavirus were similar during the periods before and after NICU-based vaccination. Conclusions On average, RV5 appeared to be well tolerated among vaccine recipients, with no increase in nosocomial rotavirus transmission observed following NICU-based rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program for otherwise eligible preterm infants seem to outweigh the possible risk of vaccine virus transmission, further studies are needed.

Background Currently, one lifetime booster of a 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for those at highest risk of invasive pneumococcal disease (IPD) 3–5 years after initial vaccination. Due to a lack of evidence on multiple revaccinations, recommendations on repeat revaccination do not exist. We aimed to determine the optimal dose and timing of PPV23 booster in high-risk groups. Methods We searched Google Scholar, Cochrane, EMBASE, Classic EMBASE, and PubMed for articles published in English and French using the MeSH terms pneumococcal infection, invasive pneumococcal disease, pneumonia, pneumo23, pneumovax 23, PPV23, and 23-valent. Articles were included if they examined dosing regimens of PPV23 (i.e., PPV23 priming and boosting) in adult populations, pediatric populations or both. Two authors independently assessed all titles and abstracts. All potentially relevant articles were chosen by consensus and retrieved for full text review. Two authors independently conducted the inclusion assessment. Results Database searches resulted in a total of 1233 articles. The review by title and abstracts resulted in the exclusion of 1170 articles, 53 articles were fully reviewed, 2 articles were identified using Google Scholar and 12 articles were finally included. The majority of evidence consistently indicated an increase in antibody response following PPV23 revaccination in both adult and pediatric populations. Evidence on multiple revaccinations was limited and mixed. Revaccination with PPV23 was well tolerated. Conclusion The majority of evidence reviewed supports PPV23 revaccination in both adult and pediatric populations. However, data on multiple booster PPV23 vaccinations in these populations is needed.

Staphylococci are common pathogens in the neonatal period. Increased survival of premature infants leads to prolonged hospital stay with associated risk factors for developing invasive staphylococcal disease. Challenges of diagnosing coagulase-negative staphylococcal infections result in conflicting definitions and inconsistent clinical practice. Resistance to methicillin influences the choice of empirical therapy.

Background We sought to determine if immune disorders early in life were associated with the later risk of Guillain-Barre syndrome, a neurological disorder thought to be infection-related. Methods We conducted a longitudinal cohort study with 16 108 819 person-years of follow-up for a population of 1 108 541 parous women in Quebec, Canada (1989-2014). The outcome was Guillain-Barre syndrome. We identified women with potential risk factors for future Guillain-Barre syndrome, including immune-mediated and rheumatological diseases, cancer, transfusion, surgical procedures and pregnancy-specific disorders. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of risk factors with later onset of Guillain-Barre syndrome, adjusted for personal characteristics of women. Results The overall incidence of Guillain-Barre syndrome was 1.42 per 100 000 person-years. Incidence was higher for women with immune-mediated (8.79 per 100 000 person-years) and rheumatological disorders (9.84 per 100 000 person-years), transfusion (4.41 per 100 000 person-years), and preeclampsia (2.62 per 100 000 person-years). Immune-mediated disorders were associated with six times the risk of Guillain-Barre syndrome (HR 6.57, 95% CI 3.58 to 12.04), rheumatological disorders with seven times the risk (HR 7.23, 95% CI 3.21 to 16.28), transfusion three times the risk (HR 3.58, 95% CI 1.83 to 6.98) and preeclampsia two times the risk (HR 2.01, 95% CI 1.29 to 3.12). Women with other potential risk factors did not have an increased risk of Guillain-Barre syndrome. Conclusions Immune-related conditions that occur early in life are associated with an increased risk of Guillain-Barre syndrome. The pathophysiology of Guillain-Barre syndrome may extend beyond infectious triggers.

Estimation of the overall effect of a vaccine program is essential, but the effect is typically estimated for a whole program. We estimated the overall effect of the Quebec rotavirus vaccine program, launched in November 2011, and the effect for each 10% increase in rotavirus vaccine coverage on pediatric hospitalizations for all-cause acute gastroenteritis. We implemented negative binomial regressions adjusted for seasonality, long-term trends, and infection dynamics, to estimate the effect of the vaccine program as: 1) a dichotomous variable, representing program presence/absence, and linear term to account for changes in trend in the period after the program began; and 2) a continuous variable, representing rotavirus vaccine coverage. Using exposure 1, the vaccine program was associated with a 51.2% (95% confidence interval (CI): 28.5, 66.7) relative decline in adjusted weekly hospitalization rates for all-cause acute gastroenteritis as of December 28, 2014. Using exposure 2, a 10% increase in rotavirus ≥1-dose coverage was associated with a 7.1% (95% CI: 3.5, 10.5) relative decline in adjusted weekly rates, with maximum coverage of 87.0% associated with a 47.2% (95% CI: 26.9, 61.9) relative decline. Estimation of the overall effect attributable to a change in vaccine coverage might be a useful addition to standard measurement of the overall effect.

Neonates in the neonatal ICU (NICU) are uniquely vulnerable to colonization and infection with pathogens such as multidrug resistant Gram-negative bacteria, which in turn are associated with increased infection-related morbidities and higher case-fatality rates. We reviewed the English, French, and German language literature published between 2015 and 2017, for reports of NICU outbreaks.A total of 39 outbreaks in NICUs were reported with Gram-negative bacteria (n = 21; 54%) causing most, and extended spectrum beta-lactamase-producing organisms being the most frequent resistance mechanism reported (n = 5). Five viral outbreaks were reported (respiratory syncytial virus = 3). A significant proportion of outbreaks (33%) did not identify a source. Whole genome sequencing was used more (n = 6 reports). The most common described infection prevention and control interventions included staff and parent education on hand hygiene, patient isolation, additional contact precautions, including discontinuation of 'kangaroo care', and cohorting. Reporting and publication bias are likely common.NICUs must be vigilant in identifying outbreaks, conduct comprehensive investigations, and implement targeted infection prevention and control strategies. Molecular epidemiology capacities are an essential element in outbreak investigation. More studies are needed to determine the added value of active colonization screening and their impact on outbreak development.

ObjectiveDespite surveillance, the Quebec Healthcare-Associated Infections Surveillance Program saw no improvement in vascular access–associated bloodstream infections in hemodialysis (HD). We aimed to determine the infection control measures recommended and implemented in Quebec’s HD units, compliance of local protocols to infection control practice guidelines, and reasons behind the low prevalence of arteriovenous fistulas.MethodsAn online survey was elaborated on the basis of the Centers for Disease Control and Prevention (CDC) and National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. The questionnaire was validated (construct, content, face validity, and reliability) and sent to all HD units in Quebec (n = 40). Results were analyzed using descriptive statistics, linear regression, and Poisson regression.ResultsThirty-seven (93%) of 40 HD units participated. Thirty (94%) of the 32 centers where central catheters are inserted have written insertion protocols. Compliance with practice guidelines is good, except for full-body draping during catheter insertion (79%) and ointment use at insertion site (3%). Prevention measures for catheter maintenance are in accordance with guidelines, except for skin disinfection with at least 0.5% chlorhexidine and 70% alcohol (67% compliance) and regular antiseptic ointment use at the insertion site (3%). Before fistula cannulation, skin preparation is suboptimal; forearm hygiene is performed in only 61% of cases. Several factors explain the low rate of fistulas, including patient preference (69%) and lack of surgical resources (39%; P = .01).ConclusionsImprovement in standardization of care according to practice guidelines is necessary. Fistula rate could be increased by improving access to surgical resources and patient education. Strategies are now being elaborated to address these findings.

Acute respiratory illness (ARI) and acute gastroenteritis (AGE) are the most common infections in children; the risk of such illness increases with daycare attendance. We estimated the risk of transmission of ARI and AGE from daycare attendees to their parents and describe measures used by families to prevent that transmission.We performed a retrospective cohort study of parents and children 12-60 months of age attending childcare centers attended by ≥60 children in the greater Québec City area, Canada. Participants were contacted at home by phone to answer a standardized questionnaire on infections that occurred in children and parents during the winter period.Overall, 374 households and 608 participants were included. AGE and ARI occurred at an incidence of 8.7 and 19 episodes per 100 child-months, respectively. Transmission to parents occurred about once in every 3 episodes for both types of infections. AGE in parents caused more frequent work absenteeism than ARI (62% vs. 34%, P0.005) with slightly longer duration (23% vs. 15% missing ≥2 days). Hand hygiene with soap was the primary household preventive measure. The 2009 pandemic may have positively influenced home hand hygiene practices overall but alcohol-based disinfection was infrequently applied.Parental risk and impact of AGE and ARI acquisition from their children are substantial. ARI occur more frequently overall among children, but parental work loss appears greater with AGE transmission. Our findings suggest that preventive practices to reduce the risk of secondary ARI and AGE transmission to parents warrants greater emphasis, evaluation and education.

Several conditions have been recognized to predispose individuals to invasive pneumococcal disease (IPD) (ie, the isolation of Streptococcus pneumoniae from a normally sterile site). Currently, individuals belonging to the groups known to be at high risk for IPD are vaccinated with the pneumococcal conjugate vaccine or the pneumococcal polysaccharide vaccine. Advisory committees in other countries have recommended adding asthma to the list of conditions that should require immunization for IPD; however, Canada has not. Accordingly, the authors of this article performed an analysis of the number of asthmatic individuals needed to vaccinate against IPD to prevent a single case, and compared the results with those for a condition already classified as high risk., BACKGROUND: The American Advisory Committee on Immunization Practices recommended the inclusion of adults with asthma in the high-risk category for pneumococcal vaccination based on a twofold increase in risk of invasive pneumococcal disease (IPD). OBJECTIVE: To determine whether, among individuals with asthma, the number needed to vaccinate (NNV) using pneumococcal conjugate vaccine (PCV)-13 or 23-valent pneumococcal polysaccharide vaccine (PPV-23) warrants its addition to the high-risk category for pneumococcal vaccination in Canada. METHODS: Using IPD incidence (per 10,000 individuals) figures from published articles (4.2 in high-risk asthmatics, 2.3 in low-risk asthmatics and 1.2 in healthy individuals), the NNV to prevent one case of IPD in asthmatics five to 17 years of age and 18 to 50 years of age was calculated, factoring in the proportion of pneumococcal serotypes included in vaccines (based on data from Quebec) and accounting for the possibility of waning vaccine efficacy (VE) using four scenarios. RESULTS: Assuming a VE of 65% for PCV-13 in asthmatics, the NNV would be 704 to 820 in low-risk and 386 to 449 in high-risk children; and 355 to 1532 in low-risk and 195 to 839 in high-risk adults (range depends on waning scenario). Assuming a VE of 65% for PPV-23 in asthmatics, the NNV would be 581 to 677 in low-risk and 318 to 371 in high-risk children; and 246 to 1059 in low-risk and 135 to 580 in high-risk adults. CONCLUSION: The NNV with both PCV-13 and PPV-23 in asthmatic children and adults is comparable with that of other high-risk conditions such as age ≥65 years. Therefore, the addition of asthma to the list of high-risk conditions for pneumococcal vaccination is warranted.

Background Only eight women out of one hundred diagnosed with ovarian epithelial cancers, which progressed to the clinical stage IV, survive 10 years. First line therapies: surgery, chemotherapy, and radiation therapy inflict very serious iatrogenic consequences. Passive immunotherapy of ovarian cancers offers only low efficacy. Prophylactic and therapeutic vaccines for ovarian cancers are not available. Interestingly, prophylactic vaccines for Hepatitis B Viruses (HBV) are very effective. Specific aim The specific aim of this work was to design, synthesize, and administer biomolecules, which would engage prophylactic, vaccination-induced immunity for HBV towards killing of ovarian cancer cells with high specificity and efficacy. Patients Tissue biopsies, ascites, and blood were acquired from the patients, whose identities were entirely concealed in accordance with the Declaration of Helsinki, pursuant to the Institutional Review Board approval, and with the Patients’ informed consent. Methods and results By biomolecular engineering, we have created a novel family of biomolecules: antibody × vaccine engineered constructs (AVEC: anti-HER-2 × HBsAg). We have collected the blood from the volunteers, and measured the titers of anti-HBV antibodies resulting from the FDA approved and CDC scheduled HBV vaccinations. We have acquired tumor biopsies, ascites, and blood from patients suffering from the advanced ovarian cancers. We have established cultures of HER-2 over-expressing epithelial ovarian cancers: OV-90, TOC-112D, SKOV-3, as well as human ovary surface epithelial (HOSE) and human artery endothelial (HAE) cells. Treatment of the HER-2+ ovarian cancer cells with AVEC: anti-HER-2 × HBsAg, accompanied by administration of blood drawn from patients with high titers of the anti-HBV antibodies, resulted in much higher therapeutic efficacy as compared to treatment with the naked anti-HER-2 antibodies alone and/or with the relevant isotype antibodies. This treatment had practically no effect upon the HOSE and HAE cells. Discussion Herein, we report attaining the great improvement in eradication efficacy of ovarian epithelial cancer cells’ by engaging prophylactic immunity against HBV; thus creating a novel paradigm for immunotherapy of ovarian cancer. We have accomplished that by designing, synthesis, and administration of AVEC. Therefore, the HBV vaccination acquired immunity mounts immune response against the vaccine, but AVEC redirect, accelerate, and amplify this immune response of all the elements of the native and adaptive immune system against ovarian cancer. Our novel paradigm of immunotherapy is currently streamlined to clinical trials also of other cancers, while also engaging prophylactic and acquired immunity. Conclusion Novel antibody-vaccine engineered constructs (AVEC) create the solid foundation for redirected, accelerated, and amplified prophylactic, HBV vaccination-induced immunity immunotherapy (RAAVIIT) of ovarian cancers.

Objectives To review systematically the published literature evaluating neuraminidase inhibitor (NI) safety and effectiveness in situations of pandemic and novel/variant influenza. Methods We searched six online databases using comprehensive search criteria for observational studies and randomized controlled trials investigating the effects of NI treatment, prophylaxis or outbreak control in patients of all ages. Results Overall, 165 studies were included (95% observational), which were generally of low methodological quality due to lack of adjustment for confounding variables. In studies reporting adjusted estimates in general populations, NI treatment appeared likely to be effective against mortality (primarily if administered within 48 h of symptom onset) and potentially effective in reducing pneumonia. NIs appeared effective in reducing secondary transmission when indicated for prophylaxis. Limited, low-quality data suggest NIs are likely safe in general populations and may be safe in pregnant women and children. Data are scarce regarding safety of NIs in adults and high-risk individuals. Conclusions Most included studies were observational, statistically underpowered and at high risk of reporting biased and/or confounded effect estimates. NI treatment appeared likely effective in reducing mortality (cause unspecified) and pneumonia in general populations, with increasing benefit when administered with 48 h of symptom onset. NI pre- or post-exposure prophylaxis is likely effective in reducing secondary transmission of influenza in a general population. Our evidence suggests NIs are likely safe to use in the general population; however, data for children and pregnant women are limited. Knowledge gaps persist in specific populations such as Aboriginals, high-risk individuals and the elderly.

Background The Advisory Committee on Immunization Practices (ACIP) recommended the inclusion of asthma as a high-risk condition that should warrant pneumococcal vaccination, but the National Advisory Committee on Immunization (NACI) in Canada has not yet done so. We aimed to determine the risk of invasive pneumococcal disease (IPD) in patients with asthma. Methods We searched Ovid Medline, EMBASE, Classic EMBASE, PubMEd and Cochrane for articles published between January 1990 and February 2013, using the MeSH terms pneumococcal infections/or invasive pneumococcal disease and asthma. Google Scholar was used to retrieve articles citing the seminal article by Talbot et al. Articles were included if they were population-based studies that evaluated the relationship between IPD and asthma. Two authors independently assessed all titles and abstracts. All potentially relevant articles were retrieved as full text and assessed for inclusion. Results The combined searches yielded 376 articles, which were reviewed by title and abstract. At this stage, 330 articles were excluded; 40 articles were excluded at the full article review stage – leaving 6 articles. Two additional articles were found through Google Scholar. The evidence reviewed consistently showed a positive association between asthma and risk of IPD. However, the magnitude of this effect was heterogeneous with adjusted odds ratios ranging from 6.7 (95% CI 1.6–27.3) in adults >18 years to 1.7 (95% CI 0.99–3.0) in individuals aged 2–49 with low-risk asthma. Conclusion The positive association between asthma and risk of IPD supports the addition of asthma as a high-risk condition warranting pneumococcal vaccination. Data on vaccine effectiveness in this population is needed.

Background CMV is the most common cause of congenital infection and may result in permanent neurodevelopmental injury including vision and hearing loss. A vaccine to prevent transmission of CMV during pregnancy or to immunocompromised persons is a public health priority. Neutralizing antibodies (nAb) to the CMV envelope glycoprotein B (gB) in natural infection are thought to confer protection, but some vaccine candidates based on this protein alone have been insufficiently immunogenic. In this FiH dose-ranging, controlled, observer-blinded study the safety and immunogenicity of an eVLP expressing the ectodomain of gB fused to transmembrane and cytoplasmic domains of the vesicular stomatitis virus G protein (gB-G) was evaluated. Method Healthy CMV-seronegative 18–40 year olds at three sites in Canada (Vancouver, Montreal, Halifax) were randomized to one of four dose formulations (0.5 µg, 1 µg, or 2 µg gB content with Alum) or 1 µg gB without Alum, or placebo given on days 0, 56, and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB binding antibody titers and avidity assessment, and nAb to CMV infection of fibroblast and epithelial cells. A Data Safety Monitoring Board was in place. Result Among 128 participants, the most common solicited local and general AEs were pain and headache, respectively. No SAEs or withdrawals occurred. A dose-dependent boosting of nAb titers was observed after doses 2 and 3, with the highest titers in the Alum-adjuvanted 2.0 µg dose recipients. Fibroblast cell nAb were seen in 100% of 2.0 µg dose recipients, and epithelial cell nAb in 31%. Epithelial cell nAb was correlated with higher geometric mean gB binding titers, and there was a correlation between fibroblast and epithelial cell nAb titers. Conclusion An eVLP CMV vaccine was immunogenic at very low doses in healthy seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and multiple doses. This phase 1 trial supports further development of this eVLP CMV vaccine candidate. ClinicalTrials.gov NCT02826798 Disclosures S. Gantt, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. C. Quach, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. D. E. Anderson, VBI Vaccines: Employee and Shareholder, Salary. F. Diaz-Mitoma, VBI Vaccines: Consultant and Shareholder, Salary. J. Langley, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial.

Background Individuals who are 2 years of age and over and at high risk for invasive pneumococcal disease (IPD) (defined as those with functional or anatomic asplenia or sickle cell disease; hepatic cirrhosis; chronic renal failure or nephrotic syndrome; HIV infection; and immunosuppression related to disease or therapy) are recommended to receive one lifetime booster dose of polysaccharide 23-valent pneumococcal vaccine (Pneu-P-23) vaccine, in addition to age- and risk-specific recommendations for the conjugate 13-valent pneumococcal vaccine (Pneu-C-13). Adults aged 65 years and over are also considered at high risk for invasive pneumococcal disease (IPD). Objective To determine the optimal time between initial vaccination with Pneu-P-23 and subsequent booster doses to protect against IPD in those at high risk for IPD. Methods The National Advisory Committee on Immunization (NACI) conducted a systematic review of the literature on booster doses of pneumococcal vaccine for individuals at high risk for IPD disease. NACI reviewed the evidence considering the target population, safety, immunogenicity, efficacy, effectiveness of the vaccines, vaccine schedules, and other aspects of the overall immunization strategy, and then approved three specific recommendations. Results For all individuals aged 2 years and over who are at high risk for IPD and who have received a dose of Pneu-P-23, re-vaccination with a second dose of Pneu-P-23 should be provided five years after the initial dose of Pneu-P-23. They should also have previously received age-appropriate doses of 13-valent conjugate pneumococcal vaccine. There is currently insufficient evidence to determine the optimal timing and number of Pneu-P-23 boosters in high-risk adults. One lifetime booster of Pneu-P-23 is currently recommended for individuals at high risk for IPD, five years after the previous dose. Given the increased risk of IPD in adults aged 65 years and older and the rapid decline in antibodies following Pneu-P-23, all individuals should receive one dose of Pneu-P-23 at age 65 years-as long as five years have passed since the previous Pneu-P-23 dose. No additional booster dose is currently recommended for this age group, if they have no medical conditions that put them at high risk for IPD. Conclusion The new and complete set of current recommendations for pneumococcal vaccines will be published in the updated "Pneumococcal" chapter in the Canadian Immunization Guide in the near future.

The National Advisory Committee on Immunization (NACI) develops recommendations for the use of vaccines for Canadians, which are summarized in the Canadian Immunization Guide (the Guide) and which is updated on a regular basis. Between March 2014 and February 2015 recommendations on five vaccines have been issued. Updates to the Guide include recommendations made for the alternative dosing administration of the human papillomavirus (HPV) vaccine in adolescents, timing of varicella zoster immune globulin (VarIg) following exposure to varicella, and the meningococcal and quadrivalent influenza vaccines, recently authorized for use in Canada. A change in recommendations for the use of pneumococcal vaccines in adults and individuals with asthma has also been made. The chapter on tick-borne encephalitis vaccine has now been removed from the Guide as this vaccine is no longer available in Canada.

BACKGROUND Interferon-gamma release assays are increasingly being used in low-incidence settings, but there is little information on whether test results influence clinical decisions in children. METHODS In June 2009, the Montreal Children's Hospital began implementing the QuantiFERON-TB Gold In-Tube (QFT) as a follow-up test to the tuberculin skin test (TST). Pediatric respirologists were asked to document how the QFT result changed their initial clinical management based on the TST. RESULTS During a 2-year period, 399 children with TST and QFT results were recruited prospectively. The median age was 13 years. In the cohort, 83% were foreign-born and 82% were Bacille Calmette-Guerin vaccinated. The QFT was negative in 5 of 11 (45.5%) children diagnosed with active tuberculosis (TB). Among 55 TST+/QFT- children evaluated as TB contacts, the negative QFT changed the treatment decision in only 3 (5.5%), and isoniazid was prescribed to the remainder. In 201 TST+/QFT- children from targeted school and immigrant screening programs, a negative QFT result was used to withhold isoniazid in 145 (72.1%) children. These children were followed for 1 year, during which no TB cases occurred. In a multivariable analysis, history of TB contact and TST induration ≥20 mm were associated with fewer changes in clinical decisions. CONCLUSIONS Our cohort study showed that pediatric respirologists used negative QFT results to withhold isoniazid in most low-risk children who were referred for a positive TST found through targeted screening programs. In contrast, in almost all TST-positive children who were evaluated as TB contacts, negative QFT results did not change clinical management.

Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2–19 years with and without cystic fibrosis (CF). Methods. Before the 2013–2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73–2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70–0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02–29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

ObjectiveWe assessed baseline prevalence, risk factors and outcomes of microcephaly in a large population of neonates.DesignRetrospective cohort study.SettingAll hospitals in the province of Quebec, Canada.Participants794 microcephalic and 1 944 010 non-microcephalic infants born between 1989 and 2012.Main outcome measuresBaseline prevalence of microcephaly and occurrence of other congenital anomalies. We estimated the association of (1) pregnancy risk factors including TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes, other), exposure to teratogens, diabetes and maternal congenital anomalies with risk of microcephaly, and (2) microcephaly with risk of infant mortality and severe morbidity, adjusted for maternal characteristics.ResultsThe overall prevalence of microcephaly was 4.1 per 10 000, ranging between 3.0 and 5.3 per 10 000 over time. Only 37% of microcephalic infants presented with other congenital anomalies. Maternal infection during pregnancy was the strongest risk factor, with 32 times the risk of microcephaly (prevalence ratio 32.38; 95% CI 22.42 to 46.75) compared with no infection. Exposure to teratogens was the next most important risk factor, with three times greater risk (prevalence ratio 3.10; 95% CI 2.37 to 4.07). Microcephaly was associated with 20 times the risk of infant mortality compared with no microcephaly (prevalence ratio 20.52; 95% CI 15.57 to 27.04) and significantly greater infant morbidity.ConclusionsIn Canada, infectious exposure during pregnancy is a strong risk factor for microcephaly, and affected infants are at higher risk of poor birth outcomes. Better monitoring of microcephaly is needed in the event that Zika or other novel viruses affect future risk.

Empirical treatment of uncomplicated urinary tract infections (UTIs) in women should be based on local susceptibility data. We aimed to generate regional and provincial cumulative antibiograms combining data from different laboratory information systems and determine the impact of basic patient characteristics on susceptibility results.All positive urine samples for Escherichia coli obtained from women aged 18-65 years old in outpatient settings between 1 April 2010 and 31 March 2015 from four hospitals in Quebec, Canada, were included. The cumulative antibiogram for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was calculated. A clinically significant difference in susceptibility profile was defined as factor(s) that lowered the susceptibility proportion below 80%.A total of 36 293 positive urine cultures were analysed. In the last year of the study, the proportion of susceptibility for ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole was 90.3%, 95.4% and 81.9%, respectively. The susceptibility proportion was80% for trimethoprim/sulfamethoxazole in the Montreal region (73.4%; 95% CI 71.1%-75.9%), whereas it remained80% for the other regions. A significant decrease in susceptibility with time was identified for ciprofloxacin (92.1%-90.3%, P 0.001) and nitrofurantoin (97.1%-95.4%, P 0.001). Increasing age, recent hospitalization and site of collection were associated with an increase in resistance for certain antibiotics.Overall, all first-line antimicrobials remain acceptable choices for empirical treatment of uncomplicated UTIs in women in Quebec. The regional variability in susceptibility data within a single province emphasizes the importance of local susceptibility data to inform the development of empirical treatment guidelines for UTIs.

Vaccination program evaluation includes assessment of vaccine uptake and direct vaccine effectiveness (VE). Often examined separately, we propose a design to estimate rotavirus vaccination coverage using controls from a rotavirus VE test-negative case-control study and to examine coverage following implementation of the Quebec, Canada, rotavirus vaccination program. We present our assumptions for using these data as a proxy for coverage in the general population, explore effects of diagnostic accuracy on coverage estimates via simulations, and validate estimates with an external source. We found 79.0% (95% confidence interval, 74.3%, 83.0%) ≥2-dose rotavirus coverage among participants eligible for publicly funded vaccination. No differences were detected between study and external coverage estimates. Simulations revealed minimal bias in estimates with high diagnostic sensitivity and specificity. We conclude that controls from a VE case-control study may be a valuable resource of coverage information when reasonable assumptions can be made for estimate generalizability; high rotavirus coverage demonstrates success of the Quebec program.

Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV) Staphylococcus epidermidis central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119 S. epidermidis CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling–area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV S. epidermidis seems more common than currently realized in the NICU, and certain hV S. epidermidis clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV S. epidermidis in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS.

Rotavirus and norovirus are among the leading causes of pediatric gastroenteritis. We examined the relative burden of pediatric gastroenteritis by etiology and compared the clinical severity of rotavirus and norovirus cases after the November 2011 implementation of publicly funded rotavirus vaccination program in Quebec.Prospective, active surveillance for acute gastroenteritis among children aged 8 weeks to less than 3 years of age was implemented at 3 hospitals. Participant demographics, clinical histories and stools were collected; stools were tested for rotavirus, norovirus and sapovirus. Risk and absolute differences of several clinical severity outcomes were compared by etiology with adjustment for patient age.From February 2012 to May 2014, 734 eligible active surveillance patients were recruited, and stools from 705 (96.0%) were tested and included in study analyses. Of these, 20.4% [95% confidence interval (CI): 16.5-24.3%] were rotavirus positive and 25.5% (95% CI: 21.3-29.8%) were norovirus positive, representing a difference of 5.1% (95% CI: 0.1-10.1%). When stratified by year, rotavirus and norovirus prevalence were similar from June 2012 to May 2013, but rotavirus prevalence was 21.4% (95% CI: 14.3-28.5%) lower than norovirus from June 2013 to May 2014. On average, rotavirus patients were more likely to be febrile, dehydrated, hospitalized and report more diarrheal episodes at the height of illness in comparison with norovirus patients of the same age.Norovirus infections were more prevalent than rotavirus infections among pediatric gastroenteritis cases hospitalized or seeking emergency care. Rotavirus cases were, on average, more clinically severe than norovirus cases among participants of the same age.

To evaluate the vaccination coverage rate of patients with JIA followed at a paediatric tertiary care centre and to determine the coverage rate for individual vaccines required as per the Quebec Immunization Protocol.Consecutive JIA patients coming for their scheduled visit were included if they were between 2 and 18 years of age and if they had an available written immunization record. Descriptive statistics were used to evaluate the proportion of children with complete vaccination status according to the Quebec Immunization Protocol at 2.5, 10.5 years and at their last clinic visit.A total of 200 patients were included. Complete vaccination according to schedule was identified in only 52% of patients at 2.5 years, 68% at 10.5 years and 61% at their last clinic visit. The vaccination coverage rate for individual vaccines was good overall with the exception of low measles, mumps and rubella vaccine coverage at 2.5 years (58%).Despite overall good vaccination coverage rate for individual vaccines, only 61% of our cohort had a complete vaccination status at their last clinic visit. Measures to optimize vaccination coverage, such as catch-up vaccination, should be implemented when possible.

The risk of infection following a visit to the emergency department is unknown. We explored this risk among elderly residents of long-term care facilities.We compared the rates of new respiratory and gastrointestinal infections among elderly residents aged 65 years and older of 22 long-term care facilities. We used standardized surveillance definitions. For each resident who visited the emergency department during the study period, we randomly selected two residents who did not visit the emergency department and matched them by facility unit, age and sex. We calculated the rates and proportions of new infections, and we used conditional logistic regression to adjust for potential confounding variables.In total, we included 1269 residents of long-term care facilities, including 424 who visited the emergency department during the study. The baseline characteristics of residents who did or did not visit the emergency department were similar, except for underlying health status (visited the emergency department: mean Charlson Comorbidity Index 6.1, standard deviation [SD] 2.5; did not visit the emergency department: mean Charlson Comorbidity index 5.5, SD 2.7; p0.001) and the proportion who had visitors (visited the emergency department: 46.9%; did not visit the emergency department: 39.2%; p = 0.01). Overall, 21 (5.0%) residents who visited the emergency department and 17 (2.0%) who did not visit the emergency department acquired new infections. The incidence of new infections was 8.3/1000 patient-days among those who visited the emergency department and 3.4/1000 patient-days among those who did not visit the emergency department. The adjusted odds ratio for the risk of infection following a visit to the emergency department was 3.9 (95% confidence interval 1.4-10.8).A visit to the emergency department was associated with more than a threefold increased risk of acute infection among elderly people. Additional precautions should be considered for residents following a visit to the emergency department.

Objective The optimal way to measure antimicrobial use in hospital populations, as a complement to surveillance of resistance is still unclear. Using respiratory isolates and antimicrobial prescriptions of nine intensive care units (ICUs), this study aimed to identify the indicator of antimicrobial use that predicted prevalence and incidence rates of resistance with the best accuracy. Methods Retrospective cohort study including all patients admitted to three neonatal (NICU), two pediatric (PICU) and four adult ICUs between April 2006 and March 2010. Ten different resistance / antimicrobial use combinations were studied. After adjustment for ICU type, indicators of antimicrobial use were successively tested in regression models, to predict resistance prevalence and incidence rates, per 4-week time period, per ICU. Binomial regression and Poisson regression were used to model prevalence and incidence rates, respectively. Multiplicative and additive models were tested, as well as no time lag and a one 4-week-period time lag. For each model, the mean absolute error (MAE) in prediction of resistance was computed. The most accurate indicator was compared to other indicators using t-tests. Results Results for all indicators were equivalent, except for 1/20 scenarios studied. In this scenario, where prevalence of carbapenem-resistant Pseudomonas sp. was predicted with carbapenem use, recommended daily doses per 100 admissions were less accurate than courses per 100 patient-days (p = 0.0006). Conclusions A single best indicator to predict antimicrobial resistance might not exist. Feasibility considerations such as ease of computation or potential external comparisons could be decisive in the choice of an indicator for surveillance of healthcare antimicrobial use.

Background Children with underlying medical conditions should receive influenza vaccine (IV) yearly; yet this remains sub-optimal. We aimed to describe our experience with a tertiary-care hospital-based influenza vaccination clinic for this at-risk population. Methods From October to December 2012, 2013, and 2014, we ran an influenza vaccination clinic at the Montreal Children's Hospital, where children with high-risk conditions come for their follow-up. Both injectable IV (IIV) and live-attenuated IV (LAIV) were offered free of charge to patients and their household contacts. Upon vaccination, parents were asked to fill a pre-piloted questionnaire. Results We vaccinated a total of 2640 high-risk children and 1912 household members during the three influenza vaccination seasons. In 2012 and 2013, 631 and 630 patients with chronic illnesses were vaccinated, compared to 1379 in 2014. Caregivers preferred LAIV primarily because no needle was involved (49.0%) and because it was perceived as less painful (46.9%). LAIV was administered to 69% (2012), 55% (2013) and 47% (2014) of high-risk children. The main reason for not receiving LAIV was because it was contra-indicated. A small fraction of children previously vaccinated with LAIV who did not present any contraindication to LAIV opted for IIV: 12/101 (11.8%) in 2013 and 16/272 (5.9%) in 2014. In 2014, this was mainly due to a previous negative experience with LAIV (11/16). Conclusion Having an influenza vaccination clinic on site at a tertiary care hospital, where children come for their scheduled visits, facilitates yearly influenza vaccination in children with chronic illnesses. LAIV is preferred by caregivers and patients, when not contraindicated.

Background In asthmatic children, 60–80% of exacerbations are triggered by respiratory pathogens and represent an important burden of illness. The impact of pathogens on exacerbation severity and treatment response remains unclear. Our aim was to describe the prevalence of respiratory pathogens in children presenting to the emergency department (ED) and investigate the association between pathogens and (i) exacerbation severity on presentation and (ii) ED treatment failure. Methods We performed a secondary analysis of the DOORWAY study, a prospective multi-center cohort of children (1–17 years) presenting to the ED with moderate or severe asthma exacerbation. All received per protocol oral corticosteroids and bronchodilators. Nasopharyngeal (NPA) secretions were analyzed by RT-PCR for 30 different pathogens. Linear and logistic multivariate regression models were used to estimate absolute risks and risk differences (RD) with their 95% CI representing average marginal effects. Results Of 958 patients with NPA specimens, 591 (61.7%) were positive for ≥ 1 pathogens; human rhinovirus (HRV) was the most prevalent (29.4%). Non-HRV infection (RD -12.9%; 95% CI -19.5; -6.3), human metapneumovirus (RD -13.6%; 95% CI -23.0%; -4.3%) and parainfluenza virus (PIV) (RD -31.7%; 95% CI -44.5%; -18.9%) were negatively associated with severity; no association was found between severity and the presence of any pathogen, co-infection, or the specific viruses HRV-A, HRV-B, HRV-C, respiratory syncytial virus, influenza (INF), enterovirus serotype D68, adenovirus or coronavirus. The risk of treatment failure in the absence of a pathogen was 12.5% (95% CI 9.0%; 16.0%). The presence of any pathogen (RD 8.2%; 95% CI 3.3%; 13.1%) and non-HRV infection as a group (RD 13.1%; 95% CI 6.4%; 19.8%), and of INF and PIV specifically (RD 24.9%; 95% CI 4.7%; 45.1% and RD 34.1%; 95% CI 7.5%; 60.7%) were positively associated with treatment failure. Conclusion In this large cohort of children with moderate or severe exacerbation, no single respiratory pathogen was associated with higher severity on presentation. However, in addition to any pathogen and non-HVR infection, INF and PIV were specifically associated with higher treatment failure in the ED, supporting the need for influenza prevention, pathogen identification at presentation and exploration of pathogen-therapy interaction. Disclosures All authors: No reported disclosures.