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Infections complicate 5%-10% of cerebrospinal fluid (CSF) shunts. We aimed to describe the characteristics and contemporary pathogens of shunt infections in children in Canada and the United States.Descriptive case series at tertiary care hospitals in Canada (N = 8) and the United States (N = 3) of children up to 18 years of age with CSF shunt infections from July 1, 2013, through June 30, 2019.There were 154 children (43% female, median age 2.7 years, 50% premature) with ≥1 CSF shunt infections. Median time between shunt placement and infection was 54 days (interquartile range, 24 days-2.3 years). Common pathogens were coagulase-negative staphylococci (N = 42; 28%), methicillin-susceptible Staphylococcus aureus (N = 24; 16%), methicillin-resistant S. aureus (N = 9; 5.9%), Pseudomonas aeruginosa (N = 9; 5.9%) and other Gram-negative bacilli (N = 14; 9.0%). Significant differences between pathogens were observed, including timing of infection (P = 0.023) and CSF leukocyte count (P = 0.0019); however, differences were not sufficient to reliably predict the causative organism based on the timing of infection or discriminate P. aeruginosa from other pathogens based on clinical features. Empiric antibiotic regimens, which included vancomycin (71%), cefotaxime or ceftriaxone (29%) and antipseudomonal beta-lactams (33%), were discordant with the pathogen isolated in five cases. There was variability between sites in the distribution of pathogens and choice of empiric antibiotics. Nine children died; 4 (44%) deaths were attributed to shunt infection.Staphylococci remain the most common cause of CSF shunt infections, although antibiotic resistant Gram-negative bacilli occur and cannot be reliably predicted based on clinical characteristics.

BackgroundPaediatric inflammatory multisystem syndrome (PIMS) is a rare but serious condition temporally associated with SARS-CoV-2 infection. Using the Canadian Paediatric Surveillance Program (CPSP), a national surveillance system, we aimed to 1) study the impact of SARS-CoV-2 linkage on clinical and laboratory characteristics, and outcomes in hospitalized children with PIMS across Canada 2) identify risk factors for ICU admission, and 3) establish the minimum national incidence of hospitalizations due to PIMS and compare it to acute COVID-19.MethodsWeekly online case reporting was distributed to the CPSP network of more than 2800 pediatricians, from March 2020 to May 2021. Comparisons were made between cases with respect to SARS-CoV-2 linkage. Multivariable modified Poisson regression was used to identify risk factors for ICU admission and Minimum incidence proportions were calculated.FindingsIn total, 406 PIMS cases were analyzed, of whom 202 (49· 8%) had a positive SARS-CoV-2 linkage, 106 (26· 1%) had a negative linkage, and 98 (24· 1%) had an unknown linkage. The median age was 5· 4 years (IQR 2· 5–9· 8), 60% were male, and 83% had no identified comorbidities. Compared to cases with a negative SARS-CoV-2 linkage, children with a positive SARS-CoV-2 linkage were older (8· 1 years [IQR 4· 2–11· 9] vs. 4· 1 years [IQR 1· 7–7· 7]; pInterpretationWhile PIMS is rare, almost 1 in 3 hospitalized children required ICU admission and respiratory/hemodynamic support, particularly those ≥ 6 years and with a positive SARS-CoV-2 linkage.FundingFinancial support for the CPSP was received from the Public Health Agency of Canada.

Previous analyses of neonatal intensive care units (NICU) antimicrobial stewardship programs have identified key contributors to overall antibiotic use, including prolonged empiric therapy48 hours for early-onset sepsis (EOS). However, most were performed in mixed NICU settings with onsite birthing units, resulting in a high proportion of inborn patient admissions. The study aimed to describe and analyze the most common reasons for antimicrobial use in an outborn tertiary care NICU.This was a 10-month review of all antimicrobial doses prescribed in a 20-bed level III NICU. The primary outcome was the total days of therapy (DOT) and length of therapy (LOT) for each clinical indication. Secondary outcomes included total DOT for each antimicrobial and appropriateness of antimicrobial courses.Of 235 antibiotic courses and 1,899 DOT (519 DOT/1,000 patient days) prescribed in 173 infants during the study period, the most common indications were suspected EOS, followed by prophylaxis. Among the 85 DOT/1,000 patient days (PD; 38 courses) prescribed for prophylaxis, 52.5 DOT/1,000 PD (25 courses; 62%) were for surgical prophylaxis. Of 17 postoperative antibiotic courses, 15 (88.2%) were deemed to be inappropriate mostly due to a duration greater than 24 hours postoperatively (Surgical prophylaxis is a common reason for antimicrobial misuse in outborn NICU. NICU-based prospective audit and feedback between neonatologists and antimicrobial stewardship teams alone may not be impactful in this setting. Partnerships with neonatologists and surgeons will be key to achieving the target of less than 24 hours of postoperative antimicrobials.· Surgical prophylaxis is a common reason for antimicrobial misuse in the NICU.. · Antimicrobial prophylaxis duration of less than 24 hours postoperatively should be encouraged.. · NICU-based prospective audit and feedback may not be impactful unless surgeons are involved..

Resume Contexte: Les facteurs de risque de complications graves de l’infection par le SRAS-CoV-2 n’ont pas ete bien etablis chez les enfants. Nous avons voulu decrire les hospitalisations pediatriques associees au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. Methodes: Nous avons procede a une etude prospective nationale en utilisant l’infrastructure du Programme canadien de surveillance pediatrique (PCSP). Les hospitalisations d’enfants ayant contracte une infection par le SRAS-CoV-2 confirmee en laboratoire de microbiologie ont ete rapportees du 8 avril au 31 decembre 2020 au moyen de questionnaires hebdomadaires en ligne distribues au reseau du PCSP, qui compte plus de 2800 pediatres. Nous avons categorise les hospitalisations comme suit : liees a la COVID-19, infections decouvertes fortuitement, ou hospitalisations pour des raisons sociales ou de controle des infections, et degage les facteurs de risque associes a la gravite de la maladie chez les patients hospitalises. Resultats: Sur les 264 hospitalisations d’enfants ayant contracte le SRAS-CoV-2 au cours de la periode de l’etude de 9 mois, 150 (56,8 %) ont ete associees a la COVID-19 et 100 (37,9 %) etaient des cas decouverts fortuitement (admission pour d’autres raisons et decouverte fortuite du SRAS-CoV-2 par depistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) representaient la majorite des cas. Parmi les hospitalisations liees a la COVID-19, 52 patients (34,7 %) etaient atteints d’une forme grave de la maladie, dont 42 (28,0 % des cas lies a la COVID-19) ont eu besoin d’une forme d’assistance respiratoire ou hemodynamique, et 59 (39,3 %) presentaient au moins 1 comorbidite sous-jacente. Les enfants atteints d’obesite, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, a l’exclusion de l’asthme, etaient plus susceptibles de presenter une forme grave ou critique de la COVID-19. Interpretation: Parmi les enfants hospitalises au Canada chez lesquels on a diagnostique une infection par le SRAS-CoV-2 au debut de la pandemie de COVID-19, la decouverte fortuite du SRAS-CoV-2 a ete frequente. Chez les enfants hospitalises pour une COVID-19 aigue, l’obesite et les comorbidites neurologiques et respiratoires ont ete associees a une gravite accrue.

Ceftriaxone is frequently used as empiric therapy because of its broad spectrum and dosing characteristics. The purpose of this study was to evaluate the appropriateness of ceftriaxone therapy among hospitalized children using drug use evaluation (DUE) methodology.Hospitalized patients who received one or fewer dose of intravenous ceftriaxone at Children's Hospital of Eastern Ontario between January 1, 2018, and June 30, 2018, were identified. Duration was defined as empiric if 72 or less and definitive if more than 72 hours. Two infectious disease physicians reviewed the charts and rated appropriateness using a previously developed scale.A total of 276 ceftriaxone courses in 248 patients (mean age 6.0 y) were reviewed. Of these, 153 (55.4%) were assessed as definitively or possibly indicated. The most common reason for inappropriate empiric use was an overly broad spectrum. Of the 120 courses given empirically for which there was no indication, the three most common reasons were lower respiratory infections (51; 42.5%), head and neck infections (18; 15.0%), and intra-abdominal infections (15; 12.5%). Of the 39 (14.1%) courses of ceftriaxone that were given for more than 72 hours, 14 (35.9%) met criteria for a definitive or possible indication.Ceftriaxone is still overused as empiric therapy. Although 85% of courses were discontinued after three doses, 14% were continued for longer than 72 hours, with approximately one-third ultimately meeting an indication. DUE using Canadian pediatric and local guidelines criteria is useful to identify clinical presentations for which narrower spectrum antimicrobials should be used.La ceftriaxone est souvent utilisée comme traitement empirique en raison de son large spectre et de ses caractéristiques posologiques. La présente étude visait à évaluer la pertinence d’un traitement à la ceftriaxone chez les enfants hospitalisés, à l’aide de la méthodologie d’évaluation de la consommation des médicaments (ÉCM).Les chercheurs ont recensé les patients hospitalisés qui ont reçu un maximum d’une dose de ceftriaxone par voie intraveineuse au Centre hospitalier pour enfants de l’est de l’Ontario entre le 1Au total, les chercheurs ont examiné 276 traitements de ceftriaxone chez 248 patients (d’un âge moyen de 6,0 ans). De ce nombre, 153 (55,4 %) ont été évalués comme définitifs ou possibles. Un trop large spectre était la principale raison d’en faire un usage empirique inapproprié. Les trois principales raisons d’administrer les 120 traitements empiriques sans indication étaient les infections des voies respiratoires inférieures (51; 42,5 %), les infections de la tête et du cou (18; 15,0 %) et les infections intra-abdominales (15; 12,5 %). Des 39 traitements de ceftriaxone (14,1 %) administrés pendant plus de 72 heures, 14 (35,9 %) avaient respecté les critères d’une indication définitive ou possible.La ceftriaxone demeure surutilisée comme traitement empirique. Même si 85 % des traitements ont été abandonnés après trois doses, 14 % se sont poursuivis plus de 72 heures, et au bout du compte, environ le tiers répondait à une indication. L’ÉCM faisant appel aux critères des directives canadiennes locales en pédiatrie est utile pour déterminer les présentations cliniques qui justifient l’utilisation d’antimicrobiens à spectre plus étroit.

In this retrospective multicenter series of 154 children with cerebrospinal fluid shunt infections, the median (interquartile range) duration of antibiotic therapy was 18 (14-26) days. The time to shunt replacement was 14 (10-19) days. Management appeared to potentially differ according to the targeted pathogen and site.

Age is the most important determinant of COVID-19 severity. Infectious disease severity by age is typically J-shaped, with infants and the elderly carrying a high burden of disease. We report on the comparative disease severity between infants and older children in a multicenter retrospective cohort study of children 0 to 17 years old admitted for acute COVID-19 from February 2020 through May 2021 in 17 pediatric hospitals. We compare clinical and laboratory characteristics and estimate the association between age group and disease severity using ordinal logistic regression. We found that infants comprised one-third of cases, but were admitted for a shorter period (median 3 days IQR 2-5 versus 4 days IQR 2-7), had a lower likelihood to have an increased C-reactive protein, and had half the odds of older children of having severe or critical disease (OR 0.50 (95% confidence interval 0.32-0.78)). Conclusion: When compared to older children, there appeared to be a lower threshold to admit infants but their length of stay was shorter and they had lower odds than older children of progressing to severe or critical disease. What is Known: • A small proportion of children infected with SARS-CoV-2 require hospitalization for acute COVID-19 with a subgroup needing specialized intensive care to treat more severe disease. • For most infectious diseases including viral respiratory tract infections, disease severity by age is J-shaped, with infants having more severe disease compared to older children. What is New: • One-third of admitted children for acute COVID-19 during the first 14 months of the pandemic were infants. • Infants had half the odds of older children of having severe or critical disease.

BACKGROUND Antimicrobial stewardship interventions to curtail the use of third-generation cephalosporins and antipseudomonal penicillins for the treatment of complicated appendicitis in children are challenging given the tendency to treat complicated disease with broad-spectrum antimicrobials. Reasons for this are unclear, but there is a paucity of contemporary microbiologic data associated with the child presenting with either acute perforated or gangrenous appendicitis. This study aimed to justify the appropriateness of an empiric regimen consisting of ampicillin, tobramycin/gentamicin plus metronidazole and to analyze duration of postoperative therapy. METHODS We conducted a retrospective cohort study from February 1, 2017, to October 31, 2018, in children who underwent appendectomy or interventional radiologic drainage for primary complicated appendicitis. The primary outcome was the proportion of patients who had a pathogen isolated from peritoneal fluid culture that was not susceptible to the recommended empiric therapy. The secondary outcomes were the total duration of antimicrobial therapy and the proportion of patients with a postoperative infectious complication within 30 days after intervention. RESULTS Of 425 children with primary acute appendicitis, 158 (37%) had complicated appendicitis at presentation. Culture was performed in 53 (40%) of the 133 who underwent a surgical or interventional radiologic intervention. The group with peritoneal cultures was more likely to present with longer symptom duration before admission [3 (interquartile range, 2-5) vs 2 (interquartile range, 1-2) days; P < 0.001] and with purulent peritonitis [47% (25/53) vs 13% (10/80); P < 0.001]. The most common pathogens isolated were anaerobes (81%), Escherichia coli (74%) and Streptococcus anginosus group (62%). Only 4% of isolated bacteria were resistant to empiric therapy. Postoperative infectious complications were documented in 23 (17%) patients and were not associated with the presence of a resistant pathogen or the choice of antimicrobial agents but with more severe disease and higher C-reactive protein values (303 vs 83 mg/L; P=0.03) at presentation. CONCLUSIONS In a cohort of previously healthy children presenting with complicated appendicitis requiring surgical drainage, the most common bacteria from peritoneal cultures continue to be S. anginosus, aminoglycoside-susceptible Gram-negative bacilli and anaerobes. In an attempt to reduce extended-spectrum cephalosporin use, these data were useful in supporting the use of metronidazole with ampicillin and an aminoglycoside, rather than third-generation cephalosporins.

Bacillus cereus is a ubiquitous Gram-positive rod seldom considered pathogenic in clinical isolates. However, it possesses multiple virulence factors explaining why it has been linked to fulminant and pyogenic infections in vulnerable hosts. Its recovery from sterile samples in immunocompromised patients cannot be disregarded. Premature infants would fall into this category. We describe the case of a neonate born at 26 weeks of gestational age, who died of a rapidly progressive B. cereus necrotizing pneumonia following suspected nosocomial acquisition. The rapidity of his course and the autopsy findings of necrosis with minimal inflammation suggest a toxin-mediated process. Pathologists should be aware of this pathogen and obtain proper microbiological samples in the presence of such autopsy findings, as the diagnosis may have infection-prevention implications in health-care settings.

Primary Subject area Neonatal-Perinatal Medicine Background Sepsis adversely impacts the survival of very low birth weight infants (VLBW), with a mortality risk up to 50%. Its diagnosis in premature infants is challenging. Conversely, prolonged antibiotic use is associated with perilous potential consequences, propelling the need to better identify those at risk of sepsis. The presence of a histological intra-amniotic inflammation (IAI) response may be associated with an increased risk of early onset sepsis (EOS). Currently, it is unknown how the diagnosis of histological IAI impacts the risk of sepsis. Objectives Our research goal is to explore histological fetal and maternal inflammation in the placenta in VLBW infants and to evaluate if specific recommendations about antibiotic management of VLBW infants with histological fetal response can be proposed. Design/Methods Retrospective cohort study of all infants < 1500 g born to a mother with histologically confirmed IAI. Demographic information about the pregnancy, delivery and postnatal course up to 28 days of life was extracted. Descriptive statistical analysis was conducted to compare the characteristics of infants with histological fetal response using χ2 test or Fisher’s exact test and Wilcoxon rank sum test or ANOVA. Results Seventy-three mother-baby pairs were reviewed. EOS prevalence (19%) in our IAI group of VLBW infants is much higher than EOS observed in all VLBW infants from the Canadian Neonatal Network database (below 3%). In our cohort, the majority had fetal inflammatory stage 1 (31.6%) and fetal inflammatory grade 0 (50%). There was no statistically significant distribution amongst the fetal stages or grades. Time to sepsis event analysis showed that the earlier fetal inflammatory grade was associated with positive cultures occurring earlier, while in the later grades there demonstrated longer latency to positive cultures. This trend was also true when looking at the maternal inflammatory stages. Nine infants who had antibiotics discontinued from day of life (DOL) 2-5 developed a positive blood culture ≤ DOL8. Conclusion Our results suggest that the presence of mild fetal inflammatory changes is associated with earlier positive cultures. We hypothesize that later grades may be associated with longer infection exposure leading to prolonged maternal antibiotics, resulting in less EOS. Majority of positive cultures were within the 3-8 day window, suggesting a role of knowing the fetal inflammatory response when deciding duration of antibiotic treatment.

BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.

We report a case of rapidly progressive necrotizing skin and soft-tissue infection caused by Bacillus cereus in an extremely low for gestational age infant. This case reminds clinicians to consider this opportunistic pathogen as the etiologic agent in fulminant necrotizing infections in vulnerable hosts, and to institute appropriate therapy in a timely fashion.

Background Aminopenicillins are recommended empiric therapy for community-acquired pneumonia (CAP). The aim of the study was to assess treatment over a 5-year period after CAP guideline publication and introduction of an antimicrobial stewardship program (ASP). Methods Using ICD-10 discharge codes for pneumonia, children less than 18 years admitted to the Children’s Hospital of Eastern Ontario January 1, 2012 and December 31, 2016 were identified. Children ≥ 2 months with consolidation were included. One day of therapy (DOT) was one or more doses of an antimicrobial given for 1 day. Results Of 1,707 patients identified, 713 met inclusion criteria. Eighteen (2.5%) had bacteria identified by culture and 79 of 265 (29.8%) had Mycoplasma pneumoniae detected. Mean DOT/1,000 patient days of aminopenicillins/penicillin (AAP) increased by 18.1% per year (95% confidence interval [CI] −0.2, 39.9%) and decreased by 37.6% per year (95% CI −56.1, −11.3%) for second- and third-generation cephalosporins in the post-ASP period. The duration of discharge antimicrobials decreased. Of 74 (10.4%) patients who had pleural fluid drained, 35 (47.3%) received more than 5 days of AAP and ≤ 5 days of second-/third-generation cephalosporins with no difference in median length of stay nor mean duration of antimicrobials. Conclusions Implementation of CAP management guidelines followed by prospective audit and feedback stewardship was associated with a sustained decrease in the use of broad-spectrum antibiotics in childhood CAP. Use of AAP should also be strongly considered in patients with effusions (even if no pathogen is identified), as clinical outcome appears similar to patients treated with broad-spectrum antimicrobials.

To characterize residual vancomycin concentrations (Cmin) and assess the relationships between Cmin, the risk of nephrotoxicity and persistent CoNS sepsis. In this 5-year retrospective study among infants treated with vancomycin, the primary outcome was the proportion of those with a steady state Cmin between 10 and 20 mg/L. The secondary outcomes were nephrotoxicity and persistent CoNS sepsis. Of 120 infants included, the median first steady state Cmin was 12.4 mg/L and 77 (64%) had a Cmin between 10 and 20 mg/L. Six percent developed nephrotoxicity. This risk was not associated with Cmin. Of the 30 infants with CoNS sepsis, 17 (57%) had persistent bacteremia, and this risk did not correlate significantly with Cmin, CoNS minimal inhibitory concentration (MIC) for vancomycin, or Cmin/MIC. The majority of infants achieved targeted levels of vancomycin, but persistent bacteremia was common. We did not identify a Cmin threshold associated with nephrotoxicity, nor with microbiological clearance.

Paradoxical immune reconstitution inflammatory syndrome is a well-described entity even in immunocompetent children, principally in association with Mycobacterium tuberculosis infections. Central nervous system involvement is a potential life-threatening form, sometimes refractory to standard treatment. We report the case of an HIV-negative refugee teenager, who presented with brain tuberculomas and pseudoabscesses responsive only to thalidomide.

Background Inappropriate antimicrobial use (AU) is recognized as a leading cause of antimicrobial resistance. However, quantifying AU in hospitals is challenging due to variability in information systems. Point prevalence surveys (PPS) provide a means to quantify AU in a cross-sectional manner within and between institutions. The aim of the study was to describe and compare the prescription patterns of AU across pediatric hospitals in Canada using PPS. Methods Two PPS (November 2018 and February 2019) were conducted at each of the 15 Canadian pediatric hospitals. For each PPS, AU data were collected for all inpatients ≤ 18 years (excluded mental health and birthing units) on the survey date. Data, including admitting diagnosis, age, comorbidities, Infectious Diseases consult, admitting service, documented pathogen(s), and antimicrobial(s) prescribed, was collected and entered into a RedCap database. Results In total, we surveyed 3826 patient-days. The mean proportion of children receiving at least one antimicrobial was 35.2% [range 25.1% to 42.9%]. Of the 1951 antimicrobials prescribed, the most common were third-generation cephalosporins [3GC] (16%; 321), aminopenicillins (15%; 297), TMP-SMX (11%; 207), piperacillin–tazobactam (10%; 193) and first-generation cephalosporins (9%; 181). Overall, the frequency of carbapenems, quinolones and vancomycin use was 4% (79), 3% (65) and 8% (151), respectively. Of the antimicrobials used for targeted or empiric therapy (n = 1541), 373 (24.2%) were for pneumonia, 278 (18%) for intra-abdominal infections and 251 (16.3%) for fever without a source. For the treatment of community-acquired pneumonia (CAP) (n = 178), aminopenicillins and 3GC use was 31% and 37%, respectively. Conclusion Our study used a standardized approach to assess AU to obtain benchmarking data for Canadian pediatric hospitals. About one-third of children hospitalized in Canadian pediatric hospitals are prescribed at least one antimicrobial. Of patients on treatment for CAP, only 31% were prescribed aminopenicillins. More detailed analysis of the rationale for AU, and assessment of appropriateness is required to fully understand antimicrobial prescribing practices in pediatric hospitals and develop stewardship initiatives. Disclosures All authors: No reported disclosures.