Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study.

OBJECTIVE: To determine the association of initial empiric antibiotic regimens with clinical outcomes in hospitalised children with severe orbital infections. DESIGN: Multi-centre observational cohort study using data from 2009 to 2018 clinical records. SETTING: Canadian children's hospitals (7) and community hospitals (3). PATIENTS: Children between 2 months and 18 years hospitalised for >24 hours with severe orbital infections. INTERVENTIONS: Empiric intravenous antibiotic regimen in the first 24 hours of hospitalisation. MAIN OUTCOME MEASURES: Length of hospital stay and surgical intervention using multivariable median regression and multivariate logistic regression, with adjustment for covariates. RESULTS: Of 1421 patients, 60.0% were male and the median age was 5.5 years (IQR 2.4-9.9). Median length of stay was 86.4 hours (IQR 56.9-137.5) and 180 (12.7%) received surgical intervention. Patients receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third generation cephalosporin and anaerobic coverage) to 19.5 hours (third generation cephalosporin, staphylococcal and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings remained unchanged in sensitivity analyses restricted to more severely ill patients. There was a twofold increase in the percentage of patients receiving the broadest empiric antibiotic regimens containing both staphylococcal and anaerobic coverage from 17.8% in 2009 to 40.3% in 2018. CONCLUSIONS: Empiric use of broad-spectrum antibiotics with staphylococci and anaerobic coverage was associated with longer length of stay and similar rates of surgery in children with orbital infections. There is an urgent need for comparative effectiveness studies of various antibiotic regimes.

Abscess volume as a predictor of surgical intervention in children hospitalized with orbital cellulitis: A multicentre cohort study.

IMPORTANCE: Orbital cellulitis with subperiosteal or orbital abscess can result in serious morbidity and mortality in children. Objective volume criterion measurement on cross-sectional imaging is a useful clinical tool to identify patients with abscess who may require surgical drainage. OBJECTIVE: To determine the predictive value of abscess volume and the optimal volume cut-point for surgical intervention. DESIGN: We conducted an observational cohort study using medical records from children hospitalized between 2009 and 2018. SETTING: Multicentre study using data from 6 children's hospitals. PARTICIPANTS: Children were included if they were between 2 months and 18 years of age and hospitalized for an orbital infection with an abscess confirmed on cross-sectional imaging. EXPOSURE: Subperiosteal or orbital abscess volume. MAIN OUTCOME AND MEASURES: The primary outcome was surgical intervention, defined as subperiosteal and/or orbital abscess drainage. Multivariable logistic regression was performed to assess the association of abscess volume with surgery. To determine the optimal abscess volume cut-point, receiver operating characteristic (ROC) analysis was performed using the Youden Index to optimize sensitivity and specificity. RESULTS: Of the 150 participants (mean [SD] age, 8.5 [4.5] years), 68 (45.3%) underwent surgical intervention. On multivariable analysis, larger abscess volume and non-medial abscess location were associated with surgical intervention (abscess volume: adjusted odds ratio [aOR], 1.46; 95% CI, 1.11-1.93; abscess location: aOR, 3.46; 95% CI, 1.4-8.58). ROC analysis demonstrated an optimal abscess volume cut-point of 1.18 mL [AUC: 0.75 (95% CI 0.67-0.83) sensitivity: 66%; specificity: 79%]. CONCLUSIONS AND RELEVANCE: In this multicentre cohort study of 150 children with subperiosteal or orbital abscess, larger abscess volume and non-medial abscess location were significant predictors of surgical intervention. Children with abscesses >1.18 mL should be considered for surgery.

Variation in the Management of Hospitalized Children With Orbital Cellulitis Over 10 Years.

OBJECTIVES: No previous study has examined the management of hospitalized children with orbital cellulitis at both children's and community hospitals across multiple sites in Canada. We describe variation and trends over time in diagnostic testing and imaging, adjunctive agents, empiric antibiotics, and surgical intervention in children hospitalized with orbital cellulitis. PATIENTS AND METHODS: Multicenter cohort study of 1579 children aged 2 months to 18 years with orbital cellulitis infections admitted to 10 hospitals from 2009 to 2018. We assessed hospital-level variation in the use of diagnostic tests, imaging, antibiotics, adjunctive agents, surgical intervention, and clinical outcomes using X2, Mann-Whitney U, and Kruskal-Wallis tests. The association between clinical management and length of stay was evaluated with median regression analysis with hospital as a fixed effect. RESULTS: There were significant differences between children's hospitals in usage of C-reactive protein tests (P < .001), computed tomography scans (P = .004), MRI scans (P = .003), intranasal decongestants (P < .001), intranasal corticosteroids (P < .001), intranasal saline spray (P < .001), and systemic corticosteroids (P < .001). Children's hospital patients had significantly longer length of hospital stay compared with community hospitals (P = .001). After adjustment, diagnostic testing, imaging, and subspecialty consults were associated with longer median length of hospital stay at children's hospitals. From 2009 to 2018, C-reactive protein test usage increased from 28.8% to 73.5% (P < .001), whereas erythrocyte sedimentation rate decreased from 31.5% to 14.1% (P < .001). CONCLUSIONS: There was significant variation in diagnostic test usage and treatments, and increases in test usage and medical intervention rates over time despite minimal changes in surgical interventions and length of stay.

Canadian infants presenting with Brief Resolved Unexplained Events (BRUEs) and validation of clinical prediction rules for risk stratification: a protocol for a multicentre, retrospective cohort study.

INTRODUCTION: Brief Resolved Unexplained Events (BRUEs) are a common presentation among infants. While most of these events are benign and self-limited, guidelines published by the American Academy of Pediatrics inaccurately identify many patients as higher-risk of a serious underlying aetiology (positive predictive value 5%). Recently, new clinical prediction rules have been derived to more accurately stratify patients. This data were however geographically limited to the USA, with no large studies to date assessing the BRUE population in a different healthcare setting. The study's aim is to describe the clinical management and outcomes of infants presenting to Canadian hospitals with BRUEs and to externally validate the BRUE clinical prediction rules in identified cases. METHODS AND ANALYSIS: This is a multicentre retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (<1 year) presenting with a BRUE at one of 11 Canadian paediatric centres between 1 January 2017 and 31 December 2021 will be included. Eligible patients will be identified using diagnostic codes.The primary outcome will be the presence of a serious underlying illness. Secondary outcomes will include BRUE recurrence and length of hospital stay. We will describe the rates of hospital admissions and whether hospitalisation was associated with an earlier diagnosis or treatment. Variation across Canadian hospitals will be assessed using intraclass correlation coefficient. To validate the newly developed clinical prediction rule, measures of goodness of fit will be evaluated. For this validation, a sample size of 1182 is required to provide a power of 80% to detect patients with a serious underlying illness with a significance level of 5%. ETHICS AND DISSEMINATION: Ethics approval has been granted by the UBC Children's and Women's Research Board (H21-02357). The results of this study will be disseminated as peer-reviewed manuscripts and presentations at national and international conferences.

Factors Associated with Surgery and Imaging Characteristics in Severe Orbital Infections.

OBJECTIVES: To evaluate risk factors associated with surgical intervention and subperiosteal/orbital abscess in hospitalized children with severe orbital infections. STUDY DESIGN: We conducted a multicenter cohort study of children 2 months to 18 years hospitalized with periorbital or orbital cellulitis from 2009 to 2018 at 10 hospitals in Canada. Clinical details were extracted, and patients were categorized as undergoing surgical or medical-only management. Primary outcome was surgical intervention and the main secondary outcome was clinically important imaging. Logistic regression was used to identify predictors. RESULTS: Of 1579 patients entered, median age was 5.4 years, 409 (25.9%) had an orbital/subperiosteal abscess, and 189 (12.0%) underwent surgery. In the adjusted analysis, the risk of surgical intervention was associated with older age (age 9 to <14: aOR 3.9, 95% CI 2.3-6.6; and age 14 to ≤18 years: aOR 7.0, 95% CI 3.4-14.1), elevated C-reactive protein >120 mg/L (aOR 2.8, 95% CI 1.3-5.9), elevated white blood cell count of 12-20 000/µL (aOR 1.7, 95% CI 1.1-2.6), proptosis (aOR 2.6, 95% CI 1.7-4.0), and subperiosteal/orbital abscess (aOR 5.3, 95% CI 3.6-7.9). There was no association with antibiotic use before hospital admission, sex, presence of a chronic disease, temperature greater than 38.0°C, and eye swollen shut. Complications were identified in 4.7% of patients, including vision loss (0.6%), intracranial extension (1.6%), and meningitis (0.8%). CONCLUSIONS: In children hospitalized with severe orbital infections, older age, elevated C-reactive protein, elevated white blood cell count, proptosis, and subperiosteal/orbital abscess were predictors of surgical intervention.

Current practices and policies regarding the use of high-flow nasal cannula on general pediatric inpatient wards in Canada.

OBJECTIVES: High-flow nasal cannula (HFNC) oxygen therapy has become a common treatment for respiratory conditions in children. To our knowledge, no study has described practice patterns for HFNC on pediatric inpatient wards in Canada. The aim of this study was to survey current practices and policies regarding the use of HFNC on the ward in children's hospitals in Canada. METHODS: We conducted a web-based survey of Pediatric Hospital Medicine section chiefs in major tertiary care hospitals in Canada. The primary outcome was the proportion of hospitals that use HFNC on the general pediatric ward. Secondary outcomes included indications for HFNC, initial and maximum flow rates, maximum FiO2, method of nutrition delivery while on HFNC, level of nursing and respiratory therapist care required, criteria for pediatric intensive care unit transfer, and subjective successes and challenges of implementing a ward-based HFNC policy. RESULTS: The section chief survey response rate was 100% (15/15). Eight centres (53%) allowed the use of HFNC outside of an intensive care setting. Six centres initiated HFNC on the ward, while two centres only accepted patients after HFNC had been initiated in an intensive care setting. Other practices and policies varied considerably from centre to centre. CONCLUSION: Our study reveals that approximately half of tertiary children's hospitals in Canada currently use HFNC on the ward and utilize a range of practices and policies. Other centres are considering implementation. Further research is needed to inform best practices for HFNC therapy, support stewardship of health care resources, and promote safe patient care.

Care and outcomes of Canadian children hospitalised with periorbital and orbital cellulitis: protocol for a multicentre, retrospective cohort study.

INTRODUCTION: Skin and soft tissue infections of the eye can be classified based on anatomic location as either anterior to the orbital septum (ie, periorbital cellulitis) or posterior to the orbital septum (ie, orbital cellulitis). These two conditions are often considered together in hospitalised children as clinical differentiation is difficult, especially in young children. Prior studies have identified variation in management of hospitalised children with orbital cellulitis; however, they have been limited either as single centre studies or by the use of administrative data which lacks clinical details important for interpreting variation in care. We aim to describe the care and outcomes of Canadian children hospitalised with periorbital and orbital cellulitis. METHOD AND ANALYSIS: This is a multisite retrospective cohort study including previously healthy children aged 2 months to 18 years admitted to hospital with periorbital or orbital cellulitis from 2009 to 2018. Clinical data from medical records from multiple Canadian hospitals will be collected, including community and academic centres. Demographic characteristics and study outcomes will be summarised using descriptive statistics, including diagnostic testing, antibiotic therapy, adjunctive therapy, surgical intervention and clinical outcomes. Variation will be described and evaluated using χ² test or Kruskal-Wallis test. Generalised linear mixed models will be used to identify predictors of surgical intervention and longer length of stay. ETHICS AND DISSEMINATION: Approval of the study by the Research Ethics Board at each participating site has been obtained prior to data extraction. Study results will be disseminated by presentations at national and international meetings and by publications in high impact open access journals. By identifying important differences in management and outcomes by each hospital, the results will identify areas where care can be improved, practice standardised, unnecessary diagnostic imaging reduced, pharmacotherapy rationalised and where trials are needed.

Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential?

Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment. We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir. Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively. Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy. Patients revealed a tubular proteinuria pattern. Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals. In 12 of 17 patients (70%) there was a significant increase in serum creatinine. This was significantly greater than literature reports of 16% with acyclovir monotherapy. The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose. We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients. The mechanism is tubulotoxicity. Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine.