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Copyright 2014 by the article author(s).Introduction: Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has emerged as the most common cause of skin and soft-tissue infections (SSTI) in the United States. A nearly three-fold increa

OBJECTIVE: The goal was to compare the clinical effectiveness of monotherapy with beta-lactams, clindamycin, or trimethoprim-sulfamethoxazole in the outpatient management of nondrained noncultured skin and soft-tissue infections (SSTIs), in a methicillin-resistant Staphylococcus aureus (MRSA)-endemic region. METHODS: A retrospective, nested, case-control trial was conducted with a cohort of patients from 5 urban pediatric practices in a community-acquired MRSA-endemic region. All subjects were treated as outpatients with oral monotherapy for nondrained noncultured SSTIs between January 2004 and March 2007. The primary outcome was treatment failure, defined as a drainage procedure, hospitalization, change in antibiotic, or second antibiotic prescription within 28 days. RESULTS: Of 2096 children with nondrained noncultured SSTIs, 104 (5.0%) were identified as experiencing treatment failure and were matched to 480 control subjects. Compared with beta-lactam therapy, clindamycin was equally effective but trimethoprim-sulfamethoxazole was associated with an increased risk of failure. Other factors independently associated with failure included initial treatment in the emergency department, presence or history of fever, and presence of either induration or a small abscess. CONCLUSIONS: Compared with beta-lactams, clindamycin monotherapy conferred no benefit, whereas trimethoprim-sulfamethoxazole was associated with an increased risk of treatment failure in a cohort of children with nondrained noncultured SSTIs who were treated as outpatients. Even in regions with endemic community-acquired MRSA, beta-lactams may still be appropriate, first-line, empiric therapy for children presenting with these infections. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients. METHODS. We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005). RESULTS. Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received >/=3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival. CONCLUSIONS. Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Our goal was to determine the cost of influenza-related hospitalization in children with community-acquired laboratory-confirmed influenza and to identify predictors of high hospitalization costs. PATIENTS AND METHODS: This was a retrospective cohort study of patients 21 years and younger hospitalized at a children's hospital with community-acquired laboratory-confirmed influenza during 4 consecutive influenza seasons (2000-2004). The main outcome measure was the direct medical cost of influenza-related hospitalizations, including the cost of diagnostics, therapeutics, room, and physician services. RESULTS: Electronic billing data were retrievable for 727 (98%) of 745 patients hospitalized for community-acquired laboratory-confirmed influenza during the study period. A total of 478 (66%) children were in a high-risk group for whom the Advisory Committee on Immunization Practices recommended influenza vaccine (patients with Advisory Committee on Immunization Practices-designated chronic medical conditions or aged 6-23 months). The mean total cost of hospitalization for influenza-related illness was 13,159 dollars (39,792 dollars for patients admitted to an ICU; 7030 dollars for patients cared for exclusively on the wards). High-risk patients had higher mean total costs (15,269 dollars) than low-risk patients (9107 dollars). Cardiac, metabolic, and neurologic/neuromuscular diseases and age of 18 to 21 years were independently associated with the highest hospitalization costs (>15th percentile). CONCLUSIONS: The cost of influenza-related hospitalizations in children may be considerably higher than previously estimated. The presence of certain Advisory Committee on Immunization Practices-designated chronic medical conditions is associated with higher influenza-related hospitalization costs. Successfully immunizing patients with these conditions has the potential for significant cost savings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS: We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS: During 2000, there were an estimated 666 pediatric cases of IA among 152,231 immunocompromised children, yielding an annual incidence of 437/100,000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49309 compared with immunocompromised children without IA ($9035). CONCLUSIONS: The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children. [ABSTRACT FROM AUTHOR]

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.

Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown., Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression., Results: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%)., Conclusions: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted., (© The Author(s) 2023. 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 inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines., Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process., Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus., Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VACCELERATE Consortium reports financial support was provided by European Union. VACCELERATE Consortium reports financial support was provided by Federal Ministry of Education and Research Bonn Office., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: 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., Methods: 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., Results: 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%)., Conclusions: 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., (© 2022 Wiley Periodicals LLC.)

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 <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard., 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., Competing Interests: Potential conflicts of interest. B. T. F. receives funding from the Food and Drug Administration, Pfizer, and Merck and serves as a paid chair of a data and safety monitoring board (DSMB) for Astellas. R. H. serves on advisory boards for Quidel and Inflammatix; receives ASM Press book royalties (personal payments); and serves as a member of the board of directors for the Clinical Laboratories Standards Institute and as immediate past president for the Pan-American Society for Clinical Virology (both unpaid). T. E. Z. provides consultant services for T2 Biosystems and Nabriva Therapeutics. D. E. Y.’s institution receives funding from Merck, Astellas, Marion Merrel Dow Fund, Viracor-Eurofins (laboratory testing services to institution for investigator-initiated research), and Chimerix. D. E. Y. is now employed by the National Institute of Allergy and Infectious Diseases, NIH, which has paid for conference registration and fees, but this research was conducted while he was employed by Children’s Mercy Kansas City and the University of Missouri–Kansas City School of Medicine. D. E. Y. also reports serving as unpaid technical advisor to nonprofit organizations Cover the Globe and Maipelo Trust, which provide human immunodeficiency virus services to migrant or displaced children and families in Botswana. A. R. H. has patent 10,160,974 issued (Engineered cytokine- and chemokine-expressing Candida albicans strains and methods of use; no royalties collected); reports grant support from the NIH (grant K08DE026189 from the National Institute of Dental and Craniofacial Research and NIH pass-through via Duke grants [DOMINIC]); and reports serving on the Central Review Board for Non-Invasive Diagnosis of Pediatric Pulmonary Invasive Mold infections (DOMINIC) (unpaid). L. D. I. received institutional support for contracted clinical research from Astellas, Merck, Takeda, Ansun Biopharma, and Viracor-Eurofins; is a paid consultant for Takeda and paid chair of a DSMB for Merck; and serves as president of The International Society for Heart and Lung Transplantation. W. J. M. receives support from Adagio Therapeutics, Ansun Biopharma, Astellas, AstraZeneca, Eli Lilly, Enanta Pharmaceuticals, Janssen, Karius, Merck, Genentech, Gilead, Moderna, Melinta, Nabriva, Tetraphase, and Seqirus; reports consulting fees from Seqirus (to institution), the US Attorney’s Office, Southern District of Illinois (to self), McQuade Blasko Law Offices (to self), Finley Law Firm (to self), Doherty & Progar (to self), Phelan, Tucker, Mullen, Walker, Tucker, Gelman (to self), and Bailes, Craig, Yon & Sellards (to self); and reports participation on DSMB or advisory boards for Adagio Therapeutics and ProventionBio (payments to self). E. R. receives funding from Merck Sharp & Dohme (MSD), Merck, Pfizer, and Gilead; reports consulting fees from MSD and Pfizer (paid to institution); reports honoraria for lectures paid to their institution from Pfizer, MSD, and Gilead; reports travel support/payment of registration from Vianex, Pfizer, and MSD; and reports participation on advisory board(s) for MSD and Pfizer. P. K. S. reports grants from Astellas and Merck (to institution for work as clinical trial site). D. B. was a consultant for Teleflex. D. B. reports consulting fees from Precision Health (consulting agreement as of August 2021), for providing advice on the selection of polymerase chain reaction panels for outpatients in long-term care facilities and educating the Medical Science Liason team on their use) and Karius Diagnostics (where D. B. has been employed full time since 28 June 2021, as medical director in the Medical Affairs Division); Karius offers metagenomic next-generation sequencing for pathogens from plasma). As a full-time Karius employee, D. B. has the option to purchase stocks in the future during the initial public offering (the timing of the initial public offering is not yet known). D. B. continue to have a faculty appointment at Johns Hopkins All Children’s Hospital and hospital privileges (per diem). N. H. was a consultant for Moderna; receives funding from NIH, the Centers for Disease Control and Prevention, Quidel, and Sanofi; and serves as a Pediatric Infectious Diseases Society board member. G. M. receives funding from Astellas. P. S. P. receives support from Pfizer (research grant), Grifols, CSL Behring, Takeda, and Gilead (education and research grants); reports payment/honoraria from Pfizer and Gilead and payment for expert testimony from Gilead; reports participation on DSMB or an advisory board for Pfizer. C. M. S. reports receiving an NIH grant for the BIOPIC study, during the conduct of the study. M. G. reports NIH funding, outside the submitted work; receives royalties for being a textbook editor for Elsevier; reports personal consulting fees from ITB-Med; reports a personal honorarium for a lecture from Medscape; reports personal payments for serving on an advisory board for ATARA Biotherapeutics; and serves on the DSMB and as a consultant for Bristol Myers Squibb. S. B. H. reports honoraria for lectures on coronavirus disease 19 in Texas and office infection control from the Centers for Disease Control and Prevention. W. J. S. serves on the scientific advisory board of Sfunga (personal payments). All other authors report no potential 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) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe., Methods: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements., Results: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months., Conclusions: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: 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., Purpose: To compare models developed using LASSO versus random forest for predicting neurological dysfunction among fluoroquinolone users., Methods: 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., Results: 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., Conclusions: 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., (© 2021 John Wiley & Sons Ltd.)

Coronavirus disease 2019 (COVID-19) has resulted in approximately 5 million deaths around the world with unprecedented consequences in people's daily routines and in the global economy. Despite vast increases in time and money spent on COVID-19-related research, there is still limited information about the factors at the country level that affected COVID-19 transmission and fatality in EU. The paper focuses on the identification of these risk factors using a machine learning (ML) predictive pipeline and an associated explainability analysis. To achieve this, a hybrid dataset was created employing publicly available sources comprising heterogeneous parameters from the majority of EU countries, e.g., mobility measures, policy responses, vaccinations, and demographics/generic country-level parameters. Data pre-processing and data exploration techniques were initially applied to normalize the available data and decrease the feature dimensionality of the data problem considered. Then, a linear ε-Support Vector Machine (ε-SVM) model was employed to implement the regression task of predicting the number of deaths for each one of the three first pandemic waves (with mean square error of 0.027 for wave 1 and less than 0.02 for waves 2 and 3). Post hoc explainability analysis was finally applied to uncover the rationale behind the decision-making mechanisms of the ML pipeline and thus enhance our understanding with respect to the contribution of the selected country-level parameters to the prediction of COVID-19 deaths in EU.

Aim: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance., Objective: To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children., Design, Setting, and Participants: Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020., Intervention: On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic., Main Outcomes and Measures: The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora., Results: A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and β-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03)., Conclusions and Relevance: In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance., Trial Registration: ClinicalTrials.gov Identifier: NCT02891915.

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., (© 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.)

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 <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups., 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 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.)

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., (© 2021 British Veterinary Association.)

Background: Fluoroquinolones, one of the most commonly prescribed antibiotic classes, have been implicated in cases of central nervous system (CNS) and peripheral nervous system (PNS) adverse events, which highlights the need for epidemiologic studies of the neurological safety of fluoroquinolones., Purpose: To evaluate the safety of fluoroquinolones with regard to risk of diagnosed neurological dysfunction., Methods: We conducted a propensity score-matched inception cohort study using claims data from a commercially insured population. Our study included adults prescribed an oral fluoroquinolone or comparator antibiotic between January 2000 and September 2015 for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, uncomplicated urinary tract infection, or acute bronchitis. Our outcomes were CNS dysfunction, and four separate but complementary PNS dysfunction outcomes. Cox proportional hazards models were estimated after matching on propensity scores fitted using the variables age, sex, epilepsy, hereditary peripheral neuropathy, renal dysfunction, diabetes, gabapentinoid use, statin use, isoniazid use, and chemotherapy use., Results: Our cohort contained 976 568 individuals exposed to a fluoroquinolone antibiotic matched 1:1 with a comparator. Matching produced balance (standardized mean difference <0.1) on all variables included in the propensity score. The hazard ratio associated with fluoroquinolone exposure was 1.08 (95% confidence interval 1.05-1.11) for CNS dysfunction, and 1.09 (95% CI 1.07-1.11) for the most commonly occurring PNS dysfunction outcome., Conclusions: Fluoroquinolone antibiotic use was associated with the development of neurological dysfunction versus comparator antibiotic use in the adult population., (© 2021 John Wiley & Sons Ltd.)

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., (© 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.)

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 <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or voriconazole). Prophylaxis was administered from day 0 of HCT to day 42 or discharge. The primary outcome was proven or probable IFD at day 42 as adjudicated by blinded central review. Exploratory analysis stratified this evaluation by comparator triazole., 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., (© The Author(s) 2020. 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: Pressure ulcers are a major problem for national healthcare systems since they frequently occur in hospitalized patients, negatively affecting patients' quality of life and extending duration of hospitalization., Objective: To systematically review the available evidence regarding the incidence, prevalence, attributable length of stay and cost of hospital-acquired pressure ulcers in pediatric populations., Design: A systematic review and meta-analysis., Methods: A systematic search (March 15, 2020) was conducted in PubMed, Scopus, and ProQuest databases. Cross-sectional and cohort studies of neonates and children aged <21 years old were eligible for inclusion when full text was available in English and data for at least one of the following criteria was provided: incidence, prevalence, attributable length of stay or healthcare cost due to hospital-acquired pressure ulcers. Study quality was evaluated using the Joanna Briggs Institute Critical Appraisal Tools. Random effects models were used to synthesize data. Heterogeneity and publication bias were evaluated., Results: From the 1055 studies appeared in literature search, 21 studies were included in the systematic review and 19 were included in the meta-analysis. The overall prevalence ranged from 0.47% to 31.2% and cumulative incidence ranged from 3.7% to 27%. The pooled prevalence was estimated at 7.0% (95% confidence interval (CI): 4.3%-10.4%) and the pooled cumulative incidence at 14.9% (95% CI: 7.7%-23.9%). The pooled prevalence among neonates was 27.0% (95% CI: 22.1%-33.1%) among children aged less than 1 year old was 19.2% (95% CI: 9.4%-31.3%) and among children older than 1 year was 12.3% (95% CI: 2.3%-27.9%). The cumulative incidence of hospital-acquired pressure ulcers in neonates was 9.8% (95% CI: 2.9%-19.8%) and in children aged <1 year old was 11.3% (95% CI: 4.4%-20.7%), while no data was available to estimate this figure for children older than 1 year. The attributable length of stay ranged from 0.9 to 14.1 days and the attributable cost ranged from $894.69 to $98,730.24 (United States dollars; value of a dollar in 2020) per patient with hospital-acquired pressure ulcers., Conclusions and Implications of Key Findings: The results of this meta-analysis indicate that hospital-acquired pressure ulcers occur frequently in pediatric populations with a great variation across different age groups. Moreover, although limited data are available, it seems that hospital-acquired pressure ulcers have significant economic implications for the healthcare systems since they prolong patients' hospitalization stay; these findings further highlight the need for implementation of patient-based prevention strategies., Systematic Review Registration Number: Not registered Tweetable abstract: Hospital-acquired pressure ulcers occur frequently in pediatric populations, prolonging their hospitalization and increasing the healthcare cost., Competing Interests: Declaration of Competing Interest All authors report no conflicts of interest relevant to this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential., Methods: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved., Results: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses., Conclusions: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Healthcare workers' (HCW) seasonal influenza vaccination (SIV) is critical to prevent nosocomial influenza. However, HCW vaccination rates remain unacceptably low in many European institutions. A two-year three-step initiative was implemented at a tertiary-care pediatric hospital with 750 beds in Athens, Greece with the aim of increasing SIV among HCW., Methods: Α cross-sectional anonymous survey of HCWs was conducted during the 2015-16 influenza season with the aim to evaluate attitudes, knowledge, and specific barriers and facilitators for SIV. Stratified analysis was used to identify factors associated with no prior history of influenza vaccination. Multifaceted interventions were implemented in the 2016-2017 season. These included 1) education around influenza disease and SIV, and 2) communication of availability and opportunity (time and place) of SIV. Interventions were designed to target HCWs with the lowest SIV rates in the previous three years., Results: We achieved a 67% response rate, with 363 respondents (106 doctors, 145 nurses, 101 other hospital staff; 11 did not provide their profession). Most (64%) had not been vaccinated in the previous three years; only 14% received the vaccine annually. Non-vaccination rates were significantly higher among nurses (76%) and cleaning and food-service workers (73%) compared to doctors (40%) (P < 0.001). Protection of self, family, patients and colleagues were the most common motivations. Concerns about the safety and effectiveness of the vaccine, the belief that one does not belong to a high-risk group were the most common barriers. The interventions led to an increase in SIV uptake by the HCWs in the hospital, from 19% to 31%., Conclusions: In a country with very low reported rates of vaccination among HCWs, a simple, low-cost, tailor-made intervention strategy can lead to an increase in SIV uptake. Stratifying data according to vaccination history may reveal a diversity of targets for improvement that might otherwise be missed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 <13 years for whom the drug was not approved., (© 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.)

Echinocandins are used for treatment of invasive candidiasis, but data on their use in children are limited. We sought to describe the epidemiology of echinocandin use in hospitalized children in the United States. We performed a retrospective cohort study of children <18 years of age hospitalized between January 2005 and December 2015 and exposed to ≥1 day of a systemic antifungal agent using the Pediatric Health Information System (PHIS) database. Univariate analyses compared recipients of two echinocandin agents, caspofungin and micafungin. Crude prescribing rates of each antifungal group were calculated across hospitals and per year. The rate of antifungal agent prescribing over time was assessed using two-level mixed-effects negative binomial regression, accounting for variability in prescribing by hospital over time. From 2005 to 2015, fluconazole was prescribed most often (n = 148,859, 74.3%), followed by mould-active triazoles (n = 36,131, 18.0%), amphotericin products (n = 29,008, 14.5%), and echinocandins (n = 28,371, 14.2%). The crude rate of systemic antifungal prescribing decreased across all PHIS hospitals from 36.3 to 33.8 per 1000 admissions during the study period, but echinocandin prescribing increased from 2.2 to 7.2 per 1000 admissions. A mixed effects regression model revealed that echinocandin prescribing increased by 15.1% per year (95% CI 11.2-19.2). Echinocandin administration increased from 6.1% to 21.0% of admissions during which a systemic antifungal agent was given. In conclusion, echinocandin use has increased significantly over time, accounting for an increasing proportion of systemic antifungal prescribing in children., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Early-onset sepsis (EOS) remains a serious and often fatal illness among infants born preterm, particularly among newborn infants of the lowest gestational age. Currently, most preterm infants with very low birth weight are treated empirically with antibiotics for risk of EOS, often for prolonged periods, in the absence of a culture-confirmed infection. Retrospective studies have revealed that antibiotic exposures after birth are associated with multiple subsequent poor outcomes among preterm infants, making the risk/benefit balance of these antibiotic treatments uncertain. Gestational age is the strongest single predictor of EOS, and the majority of preterm births occur in the setting of other factors associated with risk of EOS, making it difficult to apply risk stratification strategies to preterm infants. Laboratory tests alone have a poor predictive value in preterm EOS. Delivery characteristics of extremely preterm infants present an opportunity to identify those with a lower risk of EOS and may inform decisions to initiate or extend antibiotic therapies. Our purpose for this clinical report is to provide a summary of the current epidemiology of preterm neonatal sepsis and provide guidance for the development of evidence-based approaches to sepsis risk assessment among preterm newborn infants., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

The incidence of neonatal early-onset sepsis (EOS) has declined substantially over the last 2 decades, primarily because of the implementation of evidence-based intrapartum antimicrobial therapy. However, EOS remains a serious and potentially fatal illness. Laboratory tests alone are neither sensitive nor specific enough to guide EOS management decisions. Maternal and infant clinical characteristics can help identify newborn infants who are at risk and guide the administration of empirical antibiotic therapy. The incidence of EOS, the prevalence and implications of established risk factors, the predictive value of commonly used laboratory tests, and the uncertainties in the risk/benefit balance of antibiotic exposures all vary significantly with gestational age at birth. Our purpose in this clinical report is to provide a summary of the current epidemiology of neonatal sepsis among infants born at ≥35 0/7 weeks' gestation and a framework for the development of evidence-based approaches to sepsis risk assessment among these infants., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Active daily surveillance of central-line days (CLDs) in the assessment of rates of central-line-associated bloodstream infections (CLABSIs) is time-consuming and burdensome for healthcare workers. Sampling of denominator data is a method that could reduce the time necessary to conduct active surveillance., Objective: To evaluate the accuracy of various sampling strategies in the estimation of CLABSI rates in adult and pediatric units in Greece., Methods: Daily denominator data were collected across Greece for 6 consecutive months in 33 units: 11 adult units, 4 pediatric intensive care units (PICUs), 12 neonatal intensive care units (NICUs), and 6 pediatric oncology units. Overall, 32 samples were evaluated using the following strategies: (1) 1 fixed day per week, (2) 2 fixed days per week, and (3) 1 fixed week per month. The CLDs for each month were estimated as follows: (number of sample CLDs/number of sampled days) × 30. The estimated CLDs were used to calculate CLABSI rates. The accuracy of the estimated CLABSI rates was assessed by calculating the percentage error (PE): [(observed CLABSI rates - estimated CLABSI rates)/observed CLABSI rates]., Results: Compared to other strategies, sampling over 2 fixed days per week provided the most accurate estimates of CLABSI rates for all types of units. Percentage of estimated CLABSI rates with PE ≤±5% using the strategy of 2 fixed days per week ranged between 74.6% and 88.7% in NICUs. This range was 79.4%-94.1% in pediatric onology units, 62.5%-91.7% in PICUs, and 80.3%-92.4% in adult units. Further evaluation with intraclass correlation coefficients and Bland-Altman plots indicated that the estimated CLABSI rates were reliable., Conclusion: Sampling over 2 fixed days per week provides a valid alternative to daily collection of CLABSI denominator data. Adoption of such a monitoring method could be an important step toward better and less burdensome infection control and prevention.

Background: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed., Methods: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD., Results: Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts., Conclusions: With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.

Importance: Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment., Objective: To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children., Design, Setting, and Participants: A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts., Exposures: Broad-spectrum antibiotics vs narrow-spectrum antibiotics., Main Outcomes and Measures: In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events., Results: Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868 (35%) were prescribed broad-spectrum antibiotics. Broad-spectrum antibiotics were associated with a slightly worse child quality of life (score of 90.2 for broad-spectrum antibiotics vs 91.5 for narrow-spectrum antibiotics; score difference for full matched analysis, -1.4% [95% CI, -2.4% to -0.4%]) but not with other patient-centered outcomes. Broad-spectrum treatment was associated with a higher risk of adverse events documented by the clinician (3.7% for broad-spectrum antibiotics vs 2.7% for narrow-spectrum antibiotics; risk difference for full matched analysis, 1.1% [95% CI, 0.4% to 1.8%]) and reported by the patient (35.6% for broad-spectrum antibiotics vs 25.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 12.2% [95% CI, 7.3% to 17.2%])., Conclusions and Relevance: Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

Importance: β-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other β-lactam antibiotic. However, few studies have evaluated the safety of this combination for children., Objective: To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal β-lactam antibiotic throughout the first week of hospitalization., Design, Setting, and Participants: This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal β-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.)., Main Outcomes and Measures: The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal β-lactam antibiotic., Results: A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal β-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal β-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14)., Conclusions and Relevance: Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.

Antifungal stewardship refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents in order to achieve the best clinical outcomes and minimize selective pressure and adverse events. Antifungal utilization has steadily risen over time in concert with the increase in number of immunocompromised adults and children at risk for invasive fungal infections (IFI). Challenges in diagnosing IFI often lead to delays in treatment and poorer outcomes. There are also emerging data linking prior antifungal exposure and suboptimal dosing to the emergence of antifungal resistance, particularly for Candida. Antimicrobial stewardship programs can take a multi-pronged bundle approach to ensure suitable prescribing of antifungals via post-prescription review and feedback and/or prior authorization. Institutional guidelines can also be developed to guide diagnostic testing in at-risk populations; appropriate choice, dose, and duration of antifungal agent; therapeutic drug monitoring; and opportunities for de-escalation and intravenous-to-oral conversion.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

Background: Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated., Methods: We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC > 0.12 but ≤ 2 mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC ≤ 0.12 mg/L). The primary treatment outcome was treatment failure within 10 weeks after initiation of FQ therapy., Results: From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p = 0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p = 0.06] and 8.48 [95% CI 1.24-57.97; exact-p = 0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p = 0.04)., Conclusion: Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.

Objectives: To assess whether clinical decision support, using computerized sexually transmitted infection (STI) risk assessments, results in increased STI testing of adolescents at high risk for STI., Study Design: In a 2-arm, randomized, controlled trial conducted at a single, urban, pediatric emergency department, adolescents completed a computerized sexual health survey. For patients assigned to the intervention arm, attending physicians received decision support to guide STI testing based on the sexual health survey-derived STI risk; in the usual care arm, decision support was not provided. We compared STI testing rates between the intervention and usual care groups, adjusting for potential confounding using multivariable logistic regression., Results: Of the 728 enrolled patients, 635 (87.2%) had evaluable data (323 intervention arm; 312 usual care arm). STI testing frequency was higher in the intervention group compared with the usual care group (52.3% vs 42%; aOR 2 [95% CI 1.1, 3.8]). This effect was even more pronounced among the patients who presented asymptomatic for STI (28.6 vs 8.2%; aOR 4.7 [95% CI 1.4-15.5])., Conclusions: Providing sexual health survey-derived decision support to emergency department clinicians led to increased testing rates for STI in adolescents at high risk for infection, particularly in those presenting asymptomatic for infection. Studies to understand potential barriers to decision support adherence should be undertaken to inform larger, multicenter studies that could determine the generalizability of these findings and whether this process leads to increased STI detection., Trial Registration: ClinicalTrials.gov: NCT02509572., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We attempted to validate a previously derived clinical prediction rule for candidemia in the pediatric intensive care unit. This multicenter case control study did not identify significant association of candidemia with most of the previously identified predictors. Additional study in larger cohorts with other predictor variables is needed., (© The Author 2015. 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.)

Objectives: A polymorphism in the gene encoding β-1,3-glucan synthase, the target of the echinocandin class of antifungals, results in increased in vitro MICs of the echinocandins. This has resulted in controversy surrounding use of the echinocandins for treatment of Candida parapsilosis candidaemia. We aimed to compare 30 day mortality in adults with C. parapsilosis candidaemia treated with echinocandins versus fluconazole., Methods: This is a retrospective observational cohort study. We used the Premier Perspective Database to identify adult patients with C. parapsilosis candidaemia treated with only fluconazole or only an echinocandin as definitive therapy. The primary outcome was 30 day mortality. Propensity scores were derived to estimate the probability the patient would have received either an echinocandin or fluconazole. Inverse probability of treatment weighting (IPTW) was used in a weighted logistic regression to calculate odds of 30 day mortality., Results: There were 307 unique patients with C. parapsilosis candidaemia. One hundred and twenty-six (41%) received fluconazole and 181 (59%) received an echinocandin. Age, gender, race, year of admission, need for ICU resources in the week prior to candidaemia onset, and receipt of vasopressors on the day of candidaemia onset were included in the propensity score model used to calculate inverse probability of treatment weights. Weighted logistic regression demonstrated no difference in 30 day mortality between patients receiving an echinocandin as compared with fluconazole (OR 0.82, 95% CI 0.33-2.07)., Conclusions: Our result supports the 2016 IDSA invasive candidiasis guidelines, which no longer clearly favour treatment with fluconazole over an echinocandin for C. parapsilosis candidaemia., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Candidemia causes significant morbidity and mortality among children. Removal of a central venous catheter (CVC) is often recommended for adults with candidemia to reduce persistent and metastatic infection. Pediatric-specific data on the impact of CVC retention are limited., Methods: A retrospective cohort study of inpatients <19 years with candidemia at the Children's Hospital of Philadelphia between 2000 and 2012 was performed. The final cohort included patients that had a CVC in place at time of blood culture and retained their CVC at least 1 day beyond the blood culture being positive. A structured data collection instrument was used to retrieve patient data. A discrete time failure model, adjusting for age and the complexity of clinical care before onset of candidemia, was used to assess the association of CVC retention and 30-day all-cause mortality., Results: Two hundred eighty-five patients with candidemia and a CVC in place at the time of blood culture were identified. Among these 285 patients, 30 (10%) died within 30 days. Central venous catheter retention was associated with a significant increased risk of death on a given day (odds ratio, 2.50; 95% confidence interval, 1.06-5.91)., Conclusions: Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered., (© The Author 2015. 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.)