The airway microbiome of persons with cystic fibrosis correlates with acquisition and microbiological outcomes of incident Stenotrophomonas maltophilia infection.

Rationale: Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF. Methods: pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia-negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis. Results: Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively. Conclusion: Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

The Use of Silver Oxynitrate Wound Dressings in the Treatment of Chronic Wounds: A Feasibility Pilot Study.

OBJECTIVE: To evaluate the feasibility and effectiveness of a silver oxynitrate (Ag 7 NO 11 ) dressing on wound healing in patients with stalled chronic wounds. METHODS: A prospective pilot study was conducted to determine the feasibility and effect of using silver oxynitrate dressings within an outpatient setting in Alberta, Canada. A total of 23 patients (12 women and 11 men; mean age, 66.1 ± 13.8 years) with a chronic wound that failed to heal with conventional treatment were included in the study. Wound assessments including the Bates-Jensen Wound Assessment Tool, wound-related pain, wound size, and patient quality of life (QoL) were conducted at baseline, after dressing application for 1 and 2 weeks, and during 4- and 12-week follow-ups. RESULTS: Dressing application at 1 and 2 weeks improved patients' wound healing progression as measured through significantly decreased Bates-Jensen Wound Assessment Tool scores with a more than 10% decrease at 4- and 12-week follow-up ( P < .001). Pain ( P = .004), and QoL psyche subscore ( P = .008) significantly improved at 4-week follow-ups, although wound area, perimeter, and QoL body and everyday subscores were not significantly affected. Wound size was not significantly affected. CONCLUSIONS: The silver oxynitrate dressing may improve healing progression in patients with chronic wounds, enhance patient experience by reducing wound-related pain, and improve patients' mental well-being. Further studies are warranted to elucidate the effect of silver oxynitrate dressings on wound area, perimeter, and volume measurements.

Deployment of a human-centred clinical decision support system for pulmonary embolism: evaluation of impact on quality of diagnostic decisions.

Pulmonary embolism (PE) is a serious condition that presents a diagnostic challenge for which diagnostic errors often happen. The literature suggests that a gap remains between PE diagnostic guidelines and adherence in healthcare practice. While system-level decision support tools exist, the clinical impact of a human-centred design (HCD) approach of PE diagnostic tool design is unknown. DESIGN: Before-after (with a preintervention period as non-concurrent control) design study. SETTING: Inpatient units at two tertiary care hospitals. PARTICIPANTS: General internal medicine physicians and their patients who underwent PE workups. INTERVENTION: After a 6-month preintervention period, a clinical decision support system (CDSS) for diagnosis of PE was deployed and evaluated over 6 months. A CDSS technical testing phase separated the two time periods. MEASUREMENTS: PE workups were identified in both the preintervention and CDSS intervention phases, and data were collected from medical charts. Physician reviewers assessed workup summaries (blinded to the study period) to determine adherence to evidence-based recommendations. Adherence to recommendations was quantified with a score ranging from 0 to 1.0 (the primary study outcome). Diagnostic tests ordered for PE workups were the secondary outcomes of interest. RESULTS: Overall adherence to diagnostic pathways was 0.63 in the CDSS intervention phase versus 0.60 in the preintervention phase (p=0.18), with fewer workups in the CDSS intervention phase having very low adherence scores. Further, adherence was significantly higher when PE workups included the Wells prediction rule (median adherence score=0.76 vs 0.59, p=0.002). This difference was even more pronounced when the analysis was limited to the CDSS intervention phase only (median adherence score=0.80 when Wells was used vs 0.60 when Wells was not used, p=0.001). For secondary outcomes, using both the D-dimer blood test (42.9% vs 55.7%, p=0.014) and CT pulmonary angiogram imaging (61.9% vs 75.4%, p=0.005) was lower during the CDSS intervention phase. CONCLUSION: A clinical decision support intervention with an HCD improves some aspects of the diagnostic decision, such as the selection of diagnostic tests and the use of the Wells probabilistic prediction rule for PE.

A mixed-methods needs assessment for an antimicrobial stewardship curriculum in pediatrics.

Objective: Antimicrobial stewardship (AS) education initiatives for multidisciplinary teams are most successful when addressing psychosocial factors driving antimicrobial prescribing (AP) and when they address the needs of the team to allow for a tailored approach to their education. Design: We conducted a mixed-methods embedded study as a needs assessment, involving quantitative analysis of AS concerns observed by pharmacists through an audit while attending clinical team rounds, as well as qualitative semi-structured interviews based on the Theoretical Domain Framework (TDF) to identify psychosocial barriers and facilitators for antimicrobial prescribing for an inpatient general pediatric service. We analyzed the data using deductive and inductive methods by mapping the TDF to a model for social determinants of antimicrobial prescribing (SDAP) in pediatric inpatient health care teams. Setting: The Clinical Teaching Unit (CTU) and Pediatric Intensive Care Unit (PICU), at a tertiary care pediatric hospital in Canada. Participants: Interviews (n = 23) with staff and resident physicians, nurse practitioners, and pharmacists. Results: Psychosocial facilitators and barriers for AS practice in the PICU and CTU which were identified included: collaboration, shared decision-making, locally accessible guidelines, and an overarching goal of doing right by the patient and feeling empowered as a prescriber. Some of the barriers identified included the norm of noninterference, professional comparisons, limited resources, feeling inadequately trained in AS, emotional prescribing, and a pejorative monitoring system. Conclusions: Our findings identified barriers and facilitators to AS decisions on pediatric inpatient teams as well as actionable needs in psychosocial-based AS education.

The Role of Prophage ϕSa3 in the Adaption of Staphylococcus aureus ST398 Sublineages from Human to Animal Hosts.

Staphylococcus aureus sequence type (ST) 398 is a lineage affecting both humans and livestock worldwide. However, the mechanisms underlying its clonal evolution are still not clearly elucidated. We applied whole-genome sequencing (WGS) typing to 45 S. aureus strains from China and Canada between 2005 and 2014, in order to gain insight into their evolutionary pathway. Based on WGS phylogenetic analysis, 42 isolates were assigned to the human-associated clade (I/II-GOI) and 3 isolates to livestock-associated clade (IIa). Phylogeny of ϕSa3 sequences revealed five phage groups (Groups 1-5), with Group 1 carrying ϕSa3-Group 1 (ϕSa3-G1), Group 2 carrying ϕSa3-G2, Group 3 carrying ϕSa3-G3, Group 4 carrying ϕSa3-G4 and Group 5 lacking ϕSa3. ϕSa3-G1 was only found in strains that accounted for the most ancestral human clade I, while ϕSa3-G2, ϕSa3-G3 and ϕSa3-G4 were found restricted to sublineages within clade II-GOI. Some isolates of clade II-GOI were also found to be ϕSa3-negative or resistant to methicillin which are unusual characteristics for human-adapted isolates. This study demonstrated a strong association between phylogenetic grouping and phage type, suggesting an important role of ϕSa3 prophage in the evolution of human-adapted ST398 subclones. In addition, our results suggest that this subclone slowly began to adapt to animal hosts by losing ϕSa3 and acquiring methicillin resistance, which was observed in some strains of human-associated clade II-GOI, an intermediate human to livestock transmission clade.

Effectiveness of Bio-K+ for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial.

OBJECTIVE: To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics. DESIGN: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019. SETTING: This study was conducted in 4 acute-care hospitals across an integrated health region. PATIENTS: Hospitalized patients, aged ≥55 years. METHODS: Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes. RESULTS: Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% -71.4% and 66.7%-75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68-1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89-1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias. CONCLUSIONS: Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.

Randomized trial of the safety and efficacy of anti-SARS-CoV-2 mAb in the treatment of patients with nosocomial COVID-19 (CATCO-NOS).

Background: Patients with nosocomial acquisition of COVID-19 have poor outcomes but have not been included in therapeutic trials to date. Methods: A pragmatic open-label randomized controlled trial of anti-SARS-CoV-2 monoclonal antibodies (mAb) was performed in hospitalized patients with nosocomial COVID-19 infection in acute care hospitals spanning a provincial health care network. Participants within 5 days of first positive test or symptom onset were randomized to standard of care (SOC) plus a single dose intravenous mAb treatment (bamlanivimab or casirivimab/imdevimab) or SOC alone on a 2:1 basis. The primary study endpoint was the need for invasive mechanical ventilation (IMV) or inpatient mortality by day 60 after randomization. Results: Forty-six participants were enrolled from 13 hospitals between February 14 and October 8, 2021: 31 in the mAb and 15 in the SOC arm. IMV or inpatient mortality up to day 60 occurred in 4 (12.9%) participants in the mAb versus 3 in the SOC arm (20.0%), difference of -7.1% (95% CI -22.5 to 13.4, p = 0.67). The study was terminated early due to lack of equipoise as effectiveness of anti-viral therapies and mAb was published in similar high-risk patient populations. Conclusions: The trial was underpowered to detect meaningful differences given its early termination. The study does highlight the feasibility of undertaking trials in this patient population using a pragmatic approach allowing for trial participation and treatment access across a large health care network and may serve as a template for future designs.

Historique: Les patients qui contractent une COVID-19 nosocomiale ont de mauvais résultats cliniques, mais n'ont pas fait partie des études thérapeutiques jusqu'à présent. Méthodologie: Les chercheurs ont mené une étude randomisée et contrôlée ouverte et pragmatique des anticorps monoclonaux (AcM) anti-SRAS-CoV-2 auprès de patients hospitalisés qui ont contracté une COVID-19 nosocomiale dans les hôpitaux de soins aigus d'un réseau de santé provincial. Dans les cinq jours suivant un premier test positif ou l'apparition des symptômes, les participants ont été divisés de manière randomisée entre la norme des soins (NdS) combinée à une monodose de traitement aux AcM par voie intraveineuse (bamlanivimab ou casirivimab-imdevimab) ou la NdS seule sur une base de deux pour un. Le critère d'évaluation primaire de l'étude était la ventilation mécanique invasive (VMI) ou la mortalité en milieu hospitalier le 60e jour après la randomisation. Résultats: Au total, 46 participants de 13 hôpitaux ont été inclus entre le 14 février et le 8 octobre 2021, soit 31 patients du volet des AcM et 15 du volet de la NdS. La VMI ou la mortalité en milieu hospitalier jusqu'au 60e jour a été observée chez quatre participants au volet des AcM (12,9 %) et trois participants du volet de la NdS (20,0 %), soit une différence de −7,1 % (IC à 95 %, −22,5 à 13,4, p = 0,67). L'étude a été interrompue précocement à cause de l'absence d'équilibre clinique, car des données sur l'efficacité des traitements antiviraux et des AcM ont été publiées au sujet de populations semblables de patients à haut risque. Conclusions: L'échantillon à l'étude était insuffisant pour déceler des différences significatives compte tenu de son interruption précoce. Cette recherche fait ressortir la faisabilité d'études auprès de cette population de patients au moyen d'une approche pragmatique pour y inclure des participants et accéder au traitement dans un vaste réseau de soins et pourrait servir de modèle pour concevoir d'autres études.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Stenotrophomonas maltophilia natural history and evolution in the airways of adults with cystic fibrosis.

Introduction: Stenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period. Methods: One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing. Results: S. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung. Discussion: Genomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution.

Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Effect of a Continuous Bedside Pressure Mapping System for Reducing Interface Pressures: A Randomized Clinical Trial.

Importance: Continuous bedside pressure mapping (CBPM) technology can assist in detecting skin areas with excessive interface pressure and inform efficient patient repositioning to prevent the development of pressure injuries (PI). Objective: To evaluate the efficacy of CBPM technology in reducing interface pressure and the incidence of PIs. Design, Setting, and Participants: This parallel, 2-group randomized clinical trial was performed at a tertiary acute care center. The study started to enroll participants in December 2014 and was completed in May 2018. Participants included adults partially or completely dependent for bed mobility. Statistical analysis was performed from September 2018 to December 2022. Intervention: Nursing staff using visual feedback from CBPM technology for 72 hours. Main Outcomes and Measures: Absolute number of sensing points with pressure readings greater than 40 mm Hg, mean interface pressure across all sensing points under a patient's body, proportion of participants who had pressure readings greater than 40 mm Hg, and pressure-related skin and soft tissue changes. Results: There were 678 patients recruited. After attrition, 260 allocated to the control group (151 [58.1%] male; mean [SD] age, 61.9 [18.5] years) and 247 in the intervention group (147 [59.5%] male; mean [SD] age, 63.6 [18.1] years) were included in analyses. The absolute number of sensing points with pressures greater than 40 mm Hg were 11 033 in the control group vs 9314 in the intervention group (P = .16). The mean (SD) interface pressure was 6.80 (1.63) mm Hg in the control group vs 6.62 (1.51) mm Hg in the intervention group (P = .18). The proportion of participants who had pressure readings greater than 40 mm Hg was 99.6% in both the control and intervention groups. Conclusions and Relevance: In this randomized clinical trial to evaluate the efficacy of CBPM technology in the reduction of interface pressure and the incidence of PIs in a tertiary acute care center, no statistically significant benefit was seen for any of the primary outcomes. These results suggest that longer duration of monitoring and adequately powered studies where CBPM feedback is integrated into a multifaceted intervention to prevent PI are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02325388.

Congenital SARS-CoV-2 Infection in Two Neonates with Confirmation by Viral Culture of the Placenta in One Case.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Coinfection with Strongyloides and SARS-CoV-2: A Systematic Review.

BACKGROUND: Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. METHODS: We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. RESULTS: We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. CONCLUSIONS: Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial.

BACKGROUND: Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. METHODS: In this multicenter, site-level, randomized, double-blind trial, patients aged 18-85 years received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. RESULTS: Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups. CONCLUSIONS: In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165.

The Alberta Telestewardship Network: Building a platform to enable capacity building in antimicrobial stewardship-results of an initial pilot study.

Background: Resources to improve antimicrobial stewardship (AS) are limited, but a telestewardship platform can enable capacity building and scalability. The Alberta Telestewardship Network (ATeleNet) was designed to focus on outreach across the province of Alberta, Canada, and facilitate AS activities. Methods: Outreach occurred virtually between pharmacists and physicians in hospital and long-term care settings throughout Alberta via secure, enterprise video conferencing software on both desktop and mobile devices. We used a quantitative questionnaire adapted from the telehealth usability questionnaire to capture the health provider's experience during each session. The questionnaire consisted of 39 questions, and a 5-point Likert scale was used to assess the degree of agreement and collate responses into a descriptive analysis. Results: A total of 33 pilot consultations were completed between July 6, 2020 and December 15, 2021. The majority (22, 85%) of respondents agreed that video conference-based virtual sessions are an acceptable means to provide health care and that they were able to express themselves effectively to other health care professionals (23, 88%). Respondents agreed the system was simple to use (23, 96%), and that they could become productive quickly using the system (23, 88%). Overall, 24 (92%) respondents were satisfied or very satisfied with the virtual care platform. Conclusions: We implemented and evaluated a telehealth consultation and collaborative care service between AS providers at multiple centres. AHS has since prioritized similar workflows, including access to specialists in acute care, as part of their virtual health strategy. Evaluation results will be shared with provincial stakeholders for further strategic planning and deployment.

Historique: Les ressources pour améliorer la gérance antimicrobienne (GA) sont limitées, mais une plateforme de télégérance peut favoriser le renforcement des capacités et l'échelonnabilité. L'Alberta Telestewardship Network (réseau de télégérance de l'Alberta, ou ATeleNet) a été conçu pour mettre l'accent sur le rayonnement dans la province de l'Alberta, au Canada et pour faciliter les activités de GA. Méthodologie: Le rayonnement s'est produit virtuellement entre des pharmaciens et des médecins d'établissements hospitaliers et d'établissements de soins de longue durée de l'Alberta par logiciel de visioconférence sécurisé sur des ordinateurs de bureau et des appareils mobiles. Les chercheurs ont utilisé un questionnaire quantitatif adapté du questionnaire sur la convivialité de la télésanté pour saisir l'expérience du dispensateur de soins lors de chaque séance. Le questionnaire était composé de 39 questions, et une échelle de Likert de cinq points a permis d'évaluer le degré d'entente et de recueillir les réponses dans une analyse descriptive. Résultats: Au total, les chercheurs ont effectué 33 consultations pilotes entre le 6 juillet 2020 et le 15 décembre 2021. La majorité des répondants (n = 22, 85 %) ont convenu que les séances en visioconférence représentaient un moyen acceptable de fournir des soins de santé et leur permettaient de s'exprimer avec efficacité auprès des autres professionnels de la santé (n = 23, 88 %). Les répondants ont indiqué que le système était facile à utiliser (n = 23, 96 %), et qu'ils pouvaient vite devenir productifs (n = 23, 88 %). Dans l'ensemble, 24 répondants (92 %) étaient satisfaits ou très satisfaits de la plateforme de soins virtuels. Conclusions: Les chercheurs ont lancé et évalué une consultation en télésanté et un service de soins coopératifs entre fournisseurs de GA de multiples centres. Depuis, les Services de santé de l'Alberta ont priorisé des processus de travail semblables dans leur stratégie de santé virtuelle, y compris pour l'accès à des spécialistes en soins aigus. Les résultats de l'évaluation seront transmis à des intervenants provinciaux en vue d'une planification et d'un déploiement stratégiques.

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.

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.

Exploring data reduction strategies in the analysis of continuous pressure imaging technology.

BACKGROUND: Science is becoming increasingly data intensive as digital innovations bring new capacity for continuous data generation and storage. This progress also brings challenges, as many scientific initiatives are challenged by the shear volumes of data produced. Here we present a case study of a data intensive randomized clinical trial assessing the utility of continuous pressure imaging (CPI) for reducing pressure injuries. OBJECTIVE: To explore an approach to reducing the amount of CPI data required for analyses to a manageable size without loss of critical information using a nested subset of pressure data. METHODS: Data from four enrolled study participants excluded from the analytical phase of the study were used to develop an approach to data reduction. A two-step data strategy was used. First, raw data were sampled at different frequencies (5, 30, 60, 120, and 240 s) to identify optimal measurement frequency. Second, similarity between adjacent frames was evaluated using correlation coefficients to identify position changes of enrolled study participants. Data strategy performance was evaluated through visual inspection using heat maps and time series plots. RESULTS: A sampling frequency of every 60 s provided reasonable representation of changes in interface pressure over time. This approach translated to using only 1.7% of the collected data in analyses. In the second step it was found that 160 frames within 24 h represented the pressure states of study participants. In total, only 480 frames from the 72 h of collected data would be needed for analyses without loss of information. Only ~ 0.2% of the raw data collected would be required for assessment of the primary trial outcome. CONCLUSIONS: Data reduction is an important component of big data analytics. Our two-step strategy markedly reduced the amount of data required for analyses without loss of information. This data reduction strategy, if validated, could be used in other CPI and other settings where large amounts of both temporal and spatial data must be analysed.