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Background Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. Methods This multinational observational cohort study enrolled patients aged >120 days and Results Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%–93.2%), specificity 97.1% (95.0%–98.5%), positive predictive value, 62.5% (43.7%–78.9%), and negative predictive value, 98.8% (97.2%–99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%– 97.1%); specificity, 94.7% (92.0%–96.7%); positive predictive value, 47.5% (31.5%–63.9%); and negative predictive value, 99.2% (97.7%–99.8%). Conclusions T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. Clinical Trials Registration NCT02220790.

Fluoroquinolones are associated with central (CNS) and peripheral (PNS) nervous system symptoms, and predicting the risk of these outcomes may have important clinical implications. Both LASSO and random forest are appealing modeling methods, yet it is not clear which method performs better for clinical risk prediction.To compare models developed using LASSO versus random forest for predicting neurological dysfunction among fluoroquinolone users.We developed and validated risk prediction models using claims data from a commercially insured population. The study cohort included adults dispensed an oral fluoroquinolone, and outcomes were CNS and PNS dysfunction. Model predictors included demographic variables, comorbidities and medications known to be associated with neurological symptoms, and several healthcare utilization predictors. We assessed the accuracy and calibration of these models using measures including AUC, calibration curves, and Brier scores.The underlying cohort contained 16 533 (1.18%) individuals with CNS dysfunction and 46 995 (3.34%) individuals with PNS dysfunction during 120 days of follow-up. For CNS dysfunction, LASSO had an AUC of 0.81 (95% CI: 0.80, 0.82), while random forest had an AUC of 0.80 (95% CI: 0.80, 0.81). For PNS dysfunction, LASSO had an AUC of 0.75 (95% CI: 0.74, 0.76) versus an AUC of 0.73 (95% CI: 0.73, 0.74) for random forest. Both LASSO models had better calibration, with Brier scores 0.17 (LASSO) versus 0.20 (random forest) for CNS dysfunction and 0.20 (LASSO) versus 0.25 (random forest) for PNS dysfunction.LASSO outperformed random forest in predicting CNS and PNS dysfunction among fluoroquinolone users, and should be considered for modeling when the cohort is modest in size, when the number of model predictors is modest, and when predictors are primarily binary.

To assess the potential benefit from the implementation of the Kaiser Permanente early-onset sepsis calculator (EOS-C), in terms of antibiotic use and requested laboratory tests, in a network of neonatal intensive care units (NICUs) in Greece, and to determine the incidence of early-onset sepsis (EOS) in Greek NICUs, a prospective surveillance study was conducted in 7 NICUs between April 2018 and June 2019. Data were collected for all newborns ≥ 34 weeks’ gestation receiving empiric antibiotic therapy within the first 3 days of life. The number of live births and positive blood or cerebrospinal fluid cultures within the first 3 days of life were used for calculation of EOS incidence. Evaluation of possible impact of implementing the calculator was done by comparing the clinicians’ recorded management to the calculator’s suggested course of action. The unit-specific incidence of culture-proven EOS ranged between 0 and 2.99/1000 live births. The weighted incidence rate for all 7 units was 1.8/1000 live births. Management of EOS guided by the calculator could lead to a reduction of empiric antibiotic initiation up to 100% for the group of “well-appearing” neonates and 86% for “equivocal,” lowering exposure to antibiotics by 4.2 and 3.8 days per neonate, respectively. Laboratory tests for blood cultures drawn could be reduced by up to 100% and 68%, respectively. Sensitivity of the EOS-C in identifying neonates with positive blood cultures was high. Conclusion: Management strategies based on the Kaiser Permanente neonatal sepsis calculator may significantly reduce antibiotic exposure, invasive diagnostic procedures, and hospitalizations in late preterm and term neonates.

Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period.Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD.A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%-85.3%), and NPV was over 99% (95% CI: 86.8%-99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%-84.2%) and PPV of 0% (95% CI: 0.0%-6.7%).Fungitell® BDG screening is of limited utility in diagnosing IFD in the post-HCT period, mainly due to high false-positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post-HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low.

INTRODUCTION Vaccination against the flu is the best method for the prevention of illness by influenza viruses. The objective of this study was to assess the impact of the COVID-19 pandemic on the seasonal influenza vaccination attitudes in Greece and to identify factors associated with a positive change in participants’ choice to vaccinate against the flu. METHODS This is a sub-analysis of a cross-sectional nationwide survey (n=1004) that was conducted between 28 April and 3 May 2020 using a mixed methodology for data collection: computer assisted telephone interviewing (CATI) and computer assisted web interviewing (CAWI). Sampling followed a proportionate, stratified by region, systematic procedure to ensure a nationally representative sample of the urban/rural population. Data were collected using a structured questionnaire consisting of four parts: 1) demographics;2) knowledge about COVID-19;3) attitudes toward COVID-19;and 4) practices to control COVID-19 and vaccination against the flu. RESULTS Of the respondents, 66.3% (n=665) had not been vaccinated for seasonal influenza during the 2019–2020 season, the period prior to the COVID-19 pandemic. However, of those, 21.8% showed willingness to receive the vaccine (n=145) the upcoming flu season 2020–2021. Factors independently associated with increased intention to vaccinate in those that had not been vaccinated the previous flu season included: age ≥65 years;the belief that vaccination against the flu is considered preventive against the spread of the coronavirus;not believing that coronavirus was man-made in a laboratory;and not believing that the pandemic will end once a large percentage of the population is infected. CONCLUSIONS Factors that shift public opinion in favor of seasonal flu vaccination can be utilized to design effective strategies to increase vaccination uptake. © 2021 Kopsidas I. et al.

Ceftolozane/tazobactam (C/T), a cephalosporin/beta-lactamase inhibitor combination, was evaluated in vitro vs. 10 comparators against 299 pediatric extended-spectrum-cephalosporin-resistant or carbapenem-resistant (ESC-R/CR) Gram-negative Enterobacteriaceae from three freestanding pediatric centers. Isolates were from urine or other sterile sites of children and adolescents through 21 years of age. Susceptibilities were assayed by microbroth dilution via custom Sensititre plates (Thermo Fisher Scientific). Susceptibility was determined using the Sensititre Vizion® system (Thermo Fisher Scientific). Susceptibility breakpoint criteria were those of the Clinical and Laboratory Standards Institute (CLSI) for 2017, except for colistin (EUCAST 2019). Overall, 87.5% isolates were C/T susceptible (MIC ≤2 μg/ml; MIC50/90, 0.25/4 μg/ml). Susceptibility to C/T was detected more frequently as compared to all other antimicrobials tested except for colistin (95.4%) and meropenem (97.4%). Percent susceptibility to C/T was high for E. coli (91%) and Klebsiella spp. (73.3%). C/T demonstrated good in-vitro activity and high potency against most beta-lactam resistant pediatric Enterobacteriaceae from three geographically diverse U.S. regions.

Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary and, when antibiotics are considered necessary, promoting the use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy and duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs (ASPs); essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient ASPs are provided.

Background Epidemiological data indicate that a large part of population needs to be vaccinated to achieve herd immunity. Hence, it is of high importance for public health officials to know whether people are going to get vaccinated for COVID-19. The objective of the present study was to examine the willingness of adult residents in Greece to receive a COVID-19 vaccine. Methods A cross-sectional was survey conducted among the adult general population of Greece between April 28, 2020 to May 03, 2020 (last week of lockdown), using a mixed methodology for data collection: Computer Assisted Telephone Interviewing (CATI) and Computer Assisted web Interviewing (CAWI). Using a sample size calculator, the target sample size was found to be around 1000 respondents. To ensure a nationally representative sample of the urban/rural population according to the Greek census 2011, a proportionate stratified by region systematic sampling procedure was used to recruit particpants. Data collection was guided through a structured questionnaire. Regarding willingness to COVID-19 vaccination, participants were asked to answer the following question: “If there was a vaccine available for the novel coronavirus, would you do it?” Results Of 1004 respondents only 57.7% stated that they are going to get vaccinated for COVID-19. Respondents aged > 65 years old, those who either themselves or a member of their household belonged to a vulnerable group, those believing that the COVID-19 virus was not developed in laboratories by humans, those believing that coronavirus is far more contagious and lethal compared to the H1N1 virus, and those believing that next waves are coming were statistically significantly more likely to be willing to get a COVID-19 vaccine. Higher knowledge score regarding symptoms, transmission routes and prevention and control measures against COVID-19 was significantly associated with higher willingness of respondents to get vaccinated. Conclusion A significant proportion of individuals in the general population are unwilling to receive a COVID-19 vaccine, stressing the need for public health officials to take immediate awareness-raising measures.

Objective:To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.Participants:The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).Methods:Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.Results:A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.Conclusions:We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.

Background Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD). Methods This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to Results A planned futility analysis demonstrated a low rate of IFD in the comparator triazole arm, so the trial was closed early. A total of 290 eligible patients, with a median age of 9.5 years (range 0.3–20.7), were randomized to caspofungin (n = 144) or a triazole (n = 146; fluconazole, n = 100; voriconazole, n = 46). The day 42 cumulative incidence of proven or probable IFD was 1.4% (95% confidence interval [CI], 0.3%–5.4%) in the caspofungin group vs 1.4% (95% CI, 0.4%–5.5%) in the triazole group (P = .99, log-rank test). When stratified by specific triazole, there was no significant difference in proven or probable IFD at day 42 between caspofungin vs fluconazole (1.0%, 95% CI, 0.1%–6.9%, P = .78) or caspofungin vs voriconazole (2.3%, 95% CI, 0.3%–15.1%, P = .69). Conclusions In pediatric HCT patients, prophylaxis with caspofungin did not significantly reduce the cumulative incidence of early proven or probable IFD compared with triazoles. Future efforts to decrease IFD-related morbidity and mortality should focus on later periods of risk. Trial Registration NCT01503515.

Background Misuse, overuse of antimicrobials and increasing rates of antimicrobial resistance are well-recognized problems throughout Europe. The aim of this survey was to describe the current pediatric antibiotic stewardship (PAS) landscape across Europe and identify gaps, in terms of national programs, networks and guidelines. Methods A survey of 17 questions was circulated in July 2019 among 24 European pediatric infectious disease researchers and clinicians, professors and heads of department on the existence of PAS programs, national networks and meetings, established competencies, metrics and guidelines. Results We received responses from 23 countries. National guidelines on the management of children with common infections treated in hospital settings exist in 15 of 23 (70%); only 8 of 15 (53%) had been updated within the previous 4 years. Most provide guidance on antibiotic initiation and duration (14 of 15, 93%), but few on when to transition from intravenous to oral antibiotics (7 of 15, 47%). National PAS competencies have only been developed in 4 countries; only 1 addressed both community and hospital prescribing. Organized national PAS networks are only established in the United Kingdom and Germany; 21 of 23, 91% countries had no agreed metric for antibiotic prescribing in children; 2 of 23 were based on daily defined doses. Conclusions Fragmented implementation of PAS programs, no agreed metrics, lack of established PAS competencies and national PAS networks along with inexistent funding is alarming in view of existing high rates of antimicrobial resistance in Europe.

Summary Background Healthcare-associated infections (HAIs) in neonatal intensive care units (NICUs) result in increased morbidity, mortality and healthcare costs. HAI rates in Greek NICUs are among the highest in Europe. There is a need to identify the factors that influence the transmission of HAIs and implementation of prevention interventions in this setting. Aim To understand healthcare workers' perceptions about HAI prevention in Greek NICUs. Methods Qualitative interviews were conducted with NICU staff (physicians and nurses) and infection prevention stakeholders (infectious diseases physicians and infection control nurses) working in three hospitals in Athens. Interviews were conducted in Greek, transcribed and translated into English, and analysed using a modified grounded theory approach. Findings Interviews were conducted with 37 respondents (20 physicians and 17 nurses). Four main barriers to HAI prevention were identified: (1) resource limitations leading to understaffing and cramped space; (2) poor knowledge about HAI prevention; (3) Greek-specific cultural norms, including hierarchy-driven decisions, a reluctance for public workers to do more than they are paid for, a belief that personal experience trumps evidence-based knowledge, and reactive rather than proactive approaches to societal challenges; and (4) lack of a national infection prevention infrastructure. Respondents believed that these barriers could be overcome through organized initiatives, high-quality HAI performance data, interpersonal interactions to build engagement around HAI prevention, and leveraging the hierarchy to promote change from the ‘top down’. Conclusion Implementing HAI prevention interventions in Greek NICUs will require consideration of contextual features surrounding the delivery of care, with particular attention paid to national culture.

International audience; Objectives: The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs).Methods: Antibiotic prescriptions and antibiograms for neonates, infants and older children with UTI admitted to a general district hospital in Central Greece were evaluated. Data covering a 5-year period were collected retrospectively from the Paediatric Department's Electronic Clinical Archive. Patients were included based on clinical and microbiological criteria. Antimicrobial susceptibility was determined by the Kirby-Bauer disk diffusion method.Results: A total of 230 patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin/clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous (i.v.) treatments for febrile (mean ± S.D., 5.4 ± 1.45 days) and afebrile UTIs (mean ± S.D., 4.4 ± 1.64 days). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim/sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%); lower resistance rates were identified for third-generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.4%) and amikacin (0.9%). Klebsiella spp. isolates were highly resistant to cefaclor (27.3%).Conclusion: High prescribing rates for amikacin and penicillins (± β-lactamase inhibitors) and prolonged i.v. treatments were observed. Escherichia coli was highly resistant to ampicillin, whilst third-generation cephalosporins exhibited greater in vitro efficacy. Establishment of antimicrobial stewardship programmes and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs.

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of the influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021–2022 season. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during this influenza season. In this technical report, we summarize recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, vaccination coverage, and detailed guidance on storage, administration, and implementation. We also provide background on inactivated and live attenuated influenza vaccine recommendations, vaccination during pregnancy and breastfeeding, diagnostic testing, and antiviral medications for treatment and chemoprophylaxis.

Background Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis. Methods Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). Results Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1–43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. Conclusions The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.

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.

In this study, we evaluated posaconazole use among hospitalized children between October 2006 and September 2015 using data from the Pediatric Health Information System. A total of 878 children (in 1949 admissions) received posaconazole, and administration increased 22% per year overall and 27% per year in children aged

OBJECTIVES: To determine if maternal intrapartum group B Streptococcus (GBS) antibiotic prophylaxis is associated with increased risk of childhood asthma, eczema, food allergy, or allergic rhinitis. METHODS: Retrospective cohort study of 14 046 children. GBS prophylaxis was defined as administration of intravenous penicillin, ampicillin, cefazolin, clindamycin, or vancomycin to the mother, ≥4 hours before delivery. Composite primary outcome was asthma, eczema, or food allergy diagnosis within 5 years of age, identified by diagnosis codes and appropriate medication prescription. Allergic rhinitis was defined by using diagnostic codes only and analyzed as a separate outcome. Analysis was a priori stratified by delivery mode and conducted by using Cox proportional hazards model adjusted for multiple confounders and covariates. Secondary analyses, restricted to children retained in cohort at 5 years’ age, were conducted by using multivariate logistic regression. RESULTS: GBS prophylaxis was not associated with increased incidence of composite outcome among infants delivered vaginally (hazard ratio: 1.13, 95% confidence interval [CI]: 0.95–1.33) or by cesarean delivery (hazard ratio: 1.08, 95% CI: 0.88–1.32). At 5 years of age, among 10 404 children retained in the study, GBS prophylaxis was not associated with the composite outcome in vaginal (odds ratio: 1.21, 95% CI: 0.96–1.52) or cesarean delivery (odds ratio: 1.17, 95% CI: 0.88–1.56) cohorts. Outcomes of asthma, eczema, food allergy, separately, and allergic rhinitis were also not associated with GBS prophylaxis. CONCLUSIONS: Intrapartum GBS prophylaxis was not associated with subsequent diagnosis of asthma, eczema, food allergy, or allergic rhinitis in the first 5 years of age.

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.

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a “low-hanging fruit” approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016–06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002), a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [−45.33, −12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a “low-hanging fruit” approach. In resource-limited settings, similar targeted stewardship interventions can be applied.

Background: \ud While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens.\ud \ud Methods: \ud Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children

BACKGROUND The misuse of antibiotics is a persistent problem in both human and veterinary medicine. While complex social and behavioural factors drive inappropriate use in human medicine, less is known about factors that impact antibiotic use in companion animal medicine. OBJECTIVE To identify the perceptions that veterinarians practicing companion animal medicine hold about the influence of financial considerations on antibiotic use. METHODS Semi-structured qualitative interviews were conducted with veterinarians practicing companion animal medicine in a major metropolitan area in the Eastern United States. Respondents were sampled purposefully, and data were analysed using a thematic analysis approach. RESULTS Interviews were conducted with 36 veterinarians from 19 practices. Veterinarians believed that their clients' willingness to pay for diagnostic testing or treatment interfered with their ability to make appropriate decisions about antibiotic use. Concerns over antibiotic expiration and subsequent financial losses limited which antibiotics veterinarians stocked. Some veterinarians feared that restricting antibiotic use to appropriate uses could harm their business and lead to economic euthanasia of their patients. CONCLUSIONS Veterinarians perceive that financial factors can impede their ability to appropriately prescribe antibiotics. Interventions that address the financial aspects of prescribing have the potential to improve antibiotic decision-making in veterinary medicine.

Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary and, when antibiotics are considered necessary, promoting use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy, duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs; essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient antibiotic stewardship programs are provided.

Objective:To audit clinical practice and implement an intervention to promote appropriate use of perioperative antimicrobial prophylaxis (PAP).Design:Prospective multicenter before-and-after study.Setting:This study was conducted in 7 surgical departments of 3 major Greek hospitals.Methods:Active PAP surveillance in adults undergoing elective surgical procedures was performed before and after implementation of a multimodal intervention. The surveillance monitored use of appropriate antimicrobial agent according to international and local guidelines, appropriate timing and duration of PAP, overall compliance with all 3 parameters and the occurrence of surgical site infections (SSIs). The intervention included education, audit, and feedback.Results:Overall, 1,447 patients were included: 768 before and 679 after intervention. Overall compliance increased from 28.2% to 43.9% (P = .001). Use of antimicrobial agents compliant to international guidelines increased from 89.6% to 96.3% (P = .001). In 4 of 7 departments, compliance with appropriate timing was already >90%; an increase from 44.3% to 73% (P = .001) and from 20.4% to 60% (P = .001), respectively, was achieved in 2 other departments, whereas a decrease from 64.1% to 10.9% (P = .001) was observed in 1 department. All but one department achieved a shorter PAP duration, and most achieved duration of ~2 days. SSIs significantly decreased from 6.9% to 4% (P = .026). After the intervention, it was 2.3 times more likely for appropriate antimicrobial use, 14.7 times more likely to administer an antimicrobial for the appropriate duration and 5.3 times more likely to administer an overall appropriate PAP.Conclusion:An intervention based on education, audit, and feedback can significantly contribute to improvement of appropriate PAP administration; further improvement in duration is needed.

Fluoroquinolone antibiotics have been implicated in cases of metabolic adverse events. This study investigated the causal association between fluoroquinolones and serious hypoglycemia in those with and without diabetes.We conducted a propensity score-matched cohort study using Optum claims data. We included adults dispensed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for specific infections of interest. The outcome was serious hypoglycemia, defined using a validated algorithm. Conditional logistic regression was used to estimate odds ratios (ORs) in diabetes and non-diabetes cohorts after matching on propensity scores fitted using confounding variables of interest.Our cohort contained 119,112 individuals with diabetes and 917,867 individuals without diabetes exposed to a fluoroquinolone, matched 1:1 with a comparator. Matching produced balance (standardized mean difference 0.1) on all variables included in the propensity score. The OR for the association between fluoroquinolones and serious hypoglycemia was 1.28 (95% confidence interval [CI]: 1.04-1.57) in the entire cohort, 1.30 (95% CI: 1.05-1.62) in individuals with diabetes, and 1.06 (95% CI: 0.53-2.13) in individuals without diabetes.Fluoroquinolone users are at an increased risk of serious hypoglycemia relative to comparator antibiotic users. This association was evident only among persons diagnosed with diabetes.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2020-2021 season.The American Academy of Pediatrics (AAP) recommends routine influenza immunization of all children without medical contraindications, starting at 6 months of age. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic. Any licensed, recommended, age-appropriate vaccine available can be administered, without preference for one product or formulation over another.Antiviral treatment of influenza with any licensed, recommended, age-appropriate influenza antiviral medication is recommended for children with suspected or confirmed influenza who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza. Antiviral treatment may be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications in whom an influenza diagnosis is confirmed or suspected, if treatment can be initiated within 48 hours of illness onset, and for children whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza.

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.

Objective:To estimate the attributable mortality, length of stay (LOS), and healthcare cost of pediatric and neonatal healthcare-acquired bloodstream infections (HA-BSIs).Design:A systematic review and meta-analysis.Methods:A systematic search (January 2000–September 2018) was conducted in PubMed, Cochrane, and CINAHL databases. Reference lists of selected articles were screened to identify additional studies. Case–control or cohort studies were eligible for inclusion when full text was available in English and data for at least 1 of the following criteria were provided: attributable or excess LOS, healthcare cost, or mortality rate due to HA-BSI. Study quality was evaluated using the Critical Appraisal Skills Programme Tool (CASP). Study selection and quality assessment were conducted by 2 independent researchers, and a third researcher was consulted to resolve any disagreements. Fixed- or random-effect models, as appropriate, were used to synthesize data. Heterogeneity and publication bias were evaluated.Results:In total, 21 studies were included in the systematic review and 13 studies were included in the meta-analysis. Attributable mean LOS ranged between 4 and 27.8 days; healthcare cost ranged between $1,642.16 and $160,804 (2019 USD) per patient with HA-BSI; and mortality rate ranged between 1.43% and 24%. The pooled mean attributable hospital LOS was 16.91 days (95% confidence interval [CI], 13.70–20.11) and the pooled attributable mortality rate was 8% (95% CI, 6–9). A meta-analysis was not conducted for cost due to lack of eligible studies.Conclusions:Pediatric HA-BSIs have a significant impact on mortality, LOS, and healthcare cost, further highlighting the need for implementation of HA-BSI prevention strategies.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS—Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators.

COACH working group.-- The paper is based on the discussion during the annual meeting of the EPI-Net project in Verona in September 2018., [Objectives] To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings., [Methods] The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS., [Results] The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review., [Conclusions] The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions.

BACKGROUND: Systems for standardizing physician payment have been shown to undervalue cognitive clinical encounters. Because health care reform emphasizes value-based approaches, we need an understanding of the way pediatric cognitive specialties are used to contribute to the provision of high-value care. We sought to investigate how clinical and administrative stakeholders perceive the value of pediatric infectious disease (PID) specialists. METHODS: We conducted qualitative interviews with a purposive sample of physicians and administrators from 5 hospitals across the United States in which children are cared for. All interviews were transcribed and systematically analyzed for common themes. RESULTS: We interviewed 97 stakeholders. Analysis revealed the following 3 domains of value: clinical, organizational, and communicative. Clinically, PID specialists were perceived to be highly valuable in treating patients with unusual infections that respond poorly to therapy, in optimizing the use of antimicrobial agents and in serving as outpatient homes for complex patients. Respondents perceived that PID specialists facilitate communication with patients and their families, the health care team and the media. PID specialists were perceived to generate value by participating in systemwide activities, including antimicrobial stewardship and infection prevention. Despite this, much of the valuable work PID specialists perform is difficult to measure causing some administrative stakeholders to question how many PID specialists are necessary to achieve high-quality care. CONCLUSIONS: With our findings, we suggest that pediatric cognitive specialties contribute value in multiple ways to the health care delivery system. Many of these domains are difficult to capture by using current metrics, which may lead administrators to overlook valuable work and to under-allocate resources.

Candidemia is the leading cause of invasive fungal infections in hospitalised children. The highest rates of candidemia have been recorded in neonates and infants

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).

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.

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.

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).

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