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Background: Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable., Methods: The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy., Results: Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence., Conclusions: Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal infections that require specific recommendations. In this article, we review the literature on AMS best practices and discuss AFS through the lens of the global core elements of AMS. We offer recommendations for best practices in AFS based on a synthesis of this evidence by an interdisciplinary expert panel of members of the Mycoses Study Group Education and Research Consortium. We also discuss research directions in this rapidly evolving field. AFS is an emerging and important component of AMS, yet requires special considerations in certain areas such as expertise, education, interventions to optimize utilization, therapeutic drug monitoring, and data analysis and reporting., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Influenza is a significant cause of childhood morbidity and death; it contributes to up to 16% of hospitalizations for respiratory illnesses worldwide. Novel rapid viral diagnostic tests, including molecular diagnostic tests, have the potential to significantly affect both time to diagnosis and selection of optimal anti-infective therapy. However, little is known about current treatment algorithms used in US hospitals. In this study, for hospitalized children in the United States, we aimed to define the current approaches to influenza diagnosis and treatment and to explore reasons for their potential variation. In this study, we aimed to define the current approaches to pediatric influenza diagnosis and treatment in US hospitals, and to explore reasons for their potential variation. Our results suggest a rise in the availability and use of rapid molecular diagnostic testing in addition to continued variability in anti-infective management, particularly with regard to antiviral use., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT., Methods: A single-center cohort of pediatric patients who underwent SOT between 2000 and 2013 was assembled retrospectively. The patients were followed for 180 days after transplant or until death to determine the presence or absence of IFD. The 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria were used to define IFD as proven or probable. The incidence of IFD, all-cause mortality rate, and case-fatality rate at 180 days were calculated., Results: Among 584 pediatric patients who underwent SOT, 13 patients sustained 14 episodes of IFD (candidiasis, aspergillosis, and mucormycosis). The overall incidence was 2.2% (14.3 IFD events per 100000 patient-days). The IFD rates according to transplant type were 12.5% (1 of 8) (heart/lung), 11.4% (4 of 35) (lung), 4.7% (8 of 172) (liver), 0% (0 of 234) (kidney), and 0% (0 of 135) (heart). Three patients with IFD (2 lung and 1 heart/lung) died, and all these deaths were deemed likely attributable to the IFD; the case-fatality rate was 21.4% (3 of 14)., Conclusions: The overall incidence of IFD in these pediatric SOT recipients was low but varied across transplant type, with heart/lung and lung recipients having the highest IFD rate. Given the attributable case-fatality rate, the risk of death resulting from IFD is potentially high. More data on groups at higher risk, such as lung transplant recipients, are needed to guide targeted antifungal prophylaxis.

Objective: In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children., Methods: ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data., Results: The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-β-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%)., Conclusions: The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection., (© The Author 2017. Published by the Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Gram-negative bacilli (GNB) account for a significant burden of infection and colonization in neonatal intensive care units (NICUs), and antibiotic resistance among these pathogens is of increasing concern., Methods: A prospective cohort study was performed in 4 NICUs between May 2009 and April 2012. The body sites from which GNB were isolated, antimicrobial susceptibilities of the GNB isolated, and antimicrobial therapy were assessed., Results: Attending neonatologists treated 3.0% (188 of 6184) of eligible infants for GNB infection; 23% of 214 GNB isolates were nonsusceptible to antimicrobial agents, including gentamicin (14.8%), piperacillin-tazobactam (9.9%), third-generation cephalosporin (7.0%), and/or carbapenem agents (4.5%). Gentamicin was the most commonly used antibiotic overall, and much of its use was empiric. However, third-generation cephalosporin agents and cefepime were used more commonly as targeted therapy for identified Gram-negative pathogens., Conclusions: One-quarter of the GNB isolates were nonsusceptible to ≥1 antibiotic. Antimicrobial stewardship strategies for reducing antimicrobial use in NICUs should be implemented., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Rates of colonization with methicillin-resistant Staphylococcus aureus (MRSA) and/or vancomycin-resistant enterococci (VRE) were determined for 1320 infants within 7 days of neonatal intensive care unit discharge. Overall, 4% and 1% of the infants were colonized with MRSA or VRE, respectively. Predictors identified in fixed-effects models were surgery during hospitalization (for MRSA colonization) and prolonged antimicrobial treatment (for VRE colonization)., (© The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The epidemiology of the colonization of infants with antimicrobial-resistant Gram-negative bacilli (GNB) at discharge from the neonatal intensive care unit (NICU) is not well understood., Methods: A multicenter study in which rectal surveillance samples for culture were obtained at NICU discharge from infants hospitalized ≥14 days was performed. Factors associated with colonization with GNB resistant to gentamicin, third/fourth-generation cephalosporin agents, or carbapenem agents were assessed by using a fixed-effects model., Results: Of these infants, 9% (119 of 1320) were colonized with ≥1 antimicrobial-resistant GNB. Prolonged treatment (≥10 days) with meropenem or third/fourth-generation cephalosporin agents or treatment for ≥5 days with a β-lactam/β-lactamase combination agent were associated with an increased risk of colonization with GNB resistant to gentamicin. Surgery and ≥5 days of treatment with third/fourth-generation cephalosporin agents, a β-lactam/β-lactamase combination agent, or metronidazole were associated with an increased risk of colonization with GNB resistant to third/fourth-generation cephalosporin agents. Female sex and prolonged treatment (≥10 days) with meropenem were associated with colonization with GNB resistant to carbapenem agents., Conclusions: Prolonged treatment with broad-spectrum antibiotics was associated with the colonization of infants with antimicrobial-resistant GNB within 7 days of NICU discharge. These findings suggest the potential for dissemination of resistant GNB from colonized infants to other NICUs, the community, or pediatric long-term care facilities. Antimicrobial stewardship efforts aimed at improving appropriate antibiotic use could have a beneficial effect on the emergence of antimicrobial-resistant GNB in the NICU population., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Considerable progress has been made in the prevention, diagnosis, and management of pediatric patients with invasive fungal disease (IFD). The reported decreasing trend in the incidence of invasive candidiasis (IC) over the past 15 years in both neonates and children has been encouraging. Nevertheless, due to the growing number of immunocompromised children at risk for IFD, this disease continues to be associated with significant morbidity and death and with increased financial burden to the health care system. Therefore, it is important to understand the contemporary epidemiology of IFD. Incidence rates of IFD in children are affected by geographical, population, and time variability. There is an ongoing effort to constantly document and update the incidence of IFD and species distribution among different pediatric populations as a means to direct preventative, diagnostic, and therapeutic resources to the most appropriate subset of patients. Children with a hematologic malignancy or a primary or secondary immunodeficiency, those undergoing solid organ or hematopoietic stem cell transplantation, and premature neonates are the major subsets of pediatric patients at risk of developing IFD. In this review, we focus on fungal disease epidemiology with a specific emphasis on the 2 most common pediatric IFDs, IC and invasive aspergillosis (IA)., (© The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antibacterial resistance is increasing globally and has been recognized as a major public health threat. Antibacterial stewardship is the coordinated effort to improve the appropriate use of antibiotics with the aim to decrease selective pressure for multidrug-resistant organisms in order to preserve the utility of antibacterial agents. This article describes the activities of the Antibacterial Resistance Leadership Group (ARLG) in the area of antibacterial stewardship. To date, the ARLG has focused intensely on development of rapid diagnostic tests, which (when coupled with educational and institutional initiatives) will enable the robust stewardship that is needed to address the current crisis of antibacterial resistance. In addition to exploring the effectiveness of stewardship techniques in community hospitals, the ARLG has also developed strategy trials to assess the feasibility of reducing antibacterial usage while preserving patient outcome., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such "top-down" methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Invasive fungal infections cause significant morbidity and mortality for children with acute myeloid leukemia (AML). Data on the comparative effectiveness of antifungal prophylaxis in this population are limited., Methods: A pediatric AML cohort was assembled from the Pediatric Health Information System database using ICD-9 codes and pharmacy data. Antifungal prophylaxis status was determined by pharmaceutical data review within 21 days of starting induction chemotherapy. Patients were followed until end of induction, death, or loss to follow-up. Cox regression analyses compared induction mortality and resources utilized between patients receiving and not receiving antifungal prophylaxis. A propensity score accounted for variation in demographic factors, location of care, and severity of illness at presentation., Results: Eight hundred seventy-one AML patients were identified; the induction case fatality rate was 3.7%. In the adjusted Cox regression model, patients receiving antifungal prophylaxis (57%) had a decreased hazard for induction mortality (hazard ratio [HR], 0.42; 95% confidence interval [CI], .19-.90). Children receiving prophylaxis were less frequently exposed to broad-spectrum gram-positive (incidence rate ratio [IRR], 0.87; 95% CI, .79-.97) and antipseudomonal β-lactam agents (HR, 0.91; 95% CI, .85-.96), had fewer blood cultures (IRR, 0.78; 95% CI, .71-.86), and had fewer chest CT scans (IRR, 0.73; 95% CI, .60-.88)., Conclusions: Antifungal prophylaxis in pediatric AML patients was associated with reduced induction mortality rates and supportive care resources. Further investigation is necessary to determine whether antifungal prophylaxis should include antimold activity.

Background: Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children., Methods: A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects., Results: We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13 years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI, $80 000-$107 200) for HO-CDI., Conclusions: Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children.

Background: The incidence and associated morbidity of Clostridium difficile (CD) infection has been increasing at an alarming rate in North America. Clostridium difficile-associated diarrhea (CDAD) is the leading cause of nosocomial diarrhea in the USA. Patients with CDAD have longer average hospital admissions and additional hospital costs. Evidence has demonstrated that patients with inflammatory bowel disease (IBD) have a higher incidence of CD in comparison to the general population. The aim of this study was to compare the rate of recurrence of CD in hospitalized pediatric patients with IBD compared to hospitalized controls. The secondary aim was to evaluate whether infection with CD resulted in a more severe disease course of IBD., Methods: This was a nested case control retrospective study of hospitalized pediatric patients. Diagnosis of CD was confirmed with stool Toxin A and B analysis. The following data were obtained from the medical records: demographic information, classification of IBD including location of disease, IBD therapy, and prior surgeries. In addition, prior hospital admissions within 1 year and antibiotic exposure were recorded. The same information was recorded following CD infection. Cases were patients with IBD and CD; two control populations were also studied: patients with CD but without IBD, and patients with IBD but without CD., Results: For aim 1, a total of 111 eligible patients with IBD and CD infection and 77 eligible control patients with CD infection were included. The rate of recurrence of CD in the IBD population was 34% compared to 7.5% in the control population (P < 0.0001). In evaluating the effect of CD infection on IBD disease severity, we compared the 111 IBD patients with CD to a second control population of 127 IBD patients without CD. 57% of IBD-CD patients were readmitted with an exacerbation of disease within 6 months of infection with CD and 67% required escalation of therapy following CD infection, compared to 30% of IBD patients without CD (P < 0.001). Of the patients with IBD and CD, 44% of the cases were new-onset IBD, 63% were on immunosuppression therapy, and 33% were on gastric acid suppression prior to infection. In comparing the IBD-CD and control CD populations, there was no significant difference in antibiotic exposure: 33% of IBD patients and 26% of control patients were on antibiotics (P < 0.2). With regard to prior hospitalization, 10% of patients with IBD were hospitalized in the 30 days prior to infection in comparison to 27% of the control CD patients (P < 0.002)., Conclusions: CD infection in patients with IBD results in a higher rate of recurrence and is associated with higher morbidity than the general population. Patients with IBD often required hospitalization and escalation of therapy following infection with CD, suggesting that CD resulted in increased severity of IBD disease. In addition, IBD patients were more likely develop community-acquired CD, while the control patients developed nosocomial infections, indicating a higher susceptibility to CD infection in patients with IBD., (Copyright © 2010 Crohn's & Crohn's & Colitis Foundation of America, Inc.)

Background: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies., Methods: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved., Results: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only., Conclusions: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.