Search

Background Despite guidelines recommending narrow-spectrum perioperative antibiotics (NSPA) as prophylaxis for most children undergoing congenital heart disease (CHD) surgery, broad-spectrum perioperative antibiotics (BSPA) are variably used, and their impact on postoperative outcomes is poorly understood. Methods We used administrative data from U.S. hospitals participating in the Vizient Clinical Data Base. Admissions from 2011 to 2018 containing a qualifying CHD surgery in children 0–17 years old were evaluated for exposure to BSPA versus NSPA. Propensity score-adjusted models were used to compare postoperative length of hospital stay (PLOS) by exposure group, while adjusting for confounders. Secondary outcomes included subsequent antimicrobial treatment and in-hospital mortality. Results Among 18 088 eligible encounters from 24 U.S. hospitals, BSPA were given in 21.4% of CHD surgeries, with mean BSPA use varying from 1.7% to 96.1% between centers. PLOS was longer for BSPA-exposed cases (adjusted hazard ratio 0.79; 95% confidence interval [CI]: 0.71–0.89, P < .0001). BSPA was associated with higher adjusted odds of subsequent antimicrobial treatment (odds ratio [OR] 1.24; 95% CI: 1.06–1.48), and there was no significant difference in adjusted mortality between exposure groups (OR 2.06; 95% CI: 1.0–4.31; P = .05). Analyses of subgroups with the most BSPA exposure, including high-complexity procedures and delayed sternal closure, also did not find (but could not exclude) a measurable benefit from BSPA on PLOS. Conclusions BSPA use was common in high-risk populations, and varied substantially between centers. Standardizing perioperative antibiotic practices between centers may reduce unnecessary broad-spectrum antibiotic exposure and improve clinical outcomes.

Reducing avoidable antimicrobial exposure to pediatric patients with cancer is achievable and necessary to promote optimal short- and long-term outcomes. Multiple evidence-based practices are already well established but should be more consistently implemented. Important opportunities exist to further improve the evidence to guide selective antimicrobial use in pediatric oncology.

Background Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. Methods A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. Results Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. Conclusions Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

BackgroundAlthough coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics.MethodsA panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion.ResultsGiven the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available.ConclusionsAntiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Background Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. Results The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. Conclusions Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Background Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. Methods This multinational observational cohort study enrolled patients aged >120 days and Results Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was −7.1% points (95% CI: −13.1% to −2.4%), favoring echinocandins. The risk difference was −0.4% (95% CI: −7.5% to 6.7%) at 30 days. Conclusions In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. Clinical Trials Registration NCT01869829.

The coronavirus disease 2019 (COVID-19) pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas reopen. Notably, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases (ID), transplant ID, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school reentry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school reentry specific to pediatric SOT recipients. Although data are limited and the COVID-19 pandemic is highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school.

BackgroundDespite increasing neonatal antibiotic stewardship efforts, understanding of interhospital variation in neonatal antibiotic use is limited.MethodsA retrospective cohort study was conducted among primarily academically affiliated hospitals participating in the Vizient Clinical Database/Resource Manager. Neonatal discharges were identified by admission age ResultsThe 118 included hospitals represented 184 716 neonatal discharges; 22 hospitals with low NCC, 56 with medium NCC, and 40 with high NCC. Mean antibiotic DOT/1000 pd was 363 (standard deviation [SD], 94) in high NCC hospitals, 243 (SD, 88) in medium NCC hospitals, and 184 (SD, 122) in low NCC hospitals. Increasing NCC was associated with higher antibiotic use, with an incidence rate ratio (IRR) of 1.95 (95% confidence interval [CI], 1.55 to 2.47) for high vs low NCC and IRR 1.31 (95% CI, 1.05 to 1.64) for medium vs low NCC. Increasing case mix index was associated with higher antibiotic use (IRR 1.86 per unit increase; 95% CI, 1.50 to 2.31).ConclusionsAggregate antibiotic use among hospitalized neonates varies based on care complexity. Substantial variation despite stratification by complexity suggests incomplete risk adjustment and/or avoidable variation in care.

Background Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. Methods This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. Results One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. Conclusions Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

Borrelia burgdorferi produces Pfs and LuxS enzymes for breakdown of the toxic byproducts of methylation reactions, producing 4,5-dihydroxy-2,3-pentanedione (DPD), adenine, and homocysteine. DPD and its spontaneously rearranged derivatives constitute a class of bacterial pheromones named autoinducer-2 (AI-2). We describe that B. burgdorferi produces DPD during laboratory cultivation. Furthermore, addition of in vitro synthesized DPD to cultured B. burgdorferi resulted in altered expression levels of a specific set of bacterial proteins, among which is the outer surface lipoprotein VlsE. While a large number of bacteria utilize homocysteine, the other LuxS product, for synthesis of methionine as part of the activated-methyl cycle, B. burgdorferi was found to lack that ability. We propose that the main function of B. burgdorferi LuxS is to synthesize DPD and that the Lyme disease spirochete utilizes a form of DPD as a pheromone to control gene expression.