Search

BackgroundPreliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019.AimWe conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013.MethodsWe analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or 'susceptible, increased exposure' from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013-2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events.ResultsFive K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event.ConclusionThe recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.

Antimicrobial resistance (AMR) in Greece is among the highest across the European Union/European Economic Area (EU/EEA), with high AMR rates even to last-line antibiotics. To better understand the clinical microbiology laboratory practices and capacities in species identification and antimicrobial susceptibility testing (AST) across public healthcare establishments in Greece, we sent a questionnaire to 98 of 128 public hospital microbiology laboratories between 1 February and 1 April 2022. Of the 73.5% (72/98) that responded, 51.4% (37/72) reported using EUCAST guidelines. Two of three laboratories used an automated instrument for species identification and AST for all laboratory samples. Broth microdilution for colistin susceptibility testing was used by 46 of the laboratories, more frequently in larger (> 400 beds) versus smaller (< 400 beds) hospitals (90.5% (19/21) vs 52.9% (27/51) respectively, p = 0.011). MALDI-TOF mass spectrometry was available in one of 10 laboratories, and more often in larger compared to smaller hospitals (p = 0.035). Although the majority of laboratories had a laboratory information system (LIS) in place, only half had the capacity to extract data directly from the LIS for the purpose of AMR surveillance; 73.6% (53/72) used restrictive antibiograms. Public microbiology laboratory AMR capacities in Greece require improvement, prioritising interventions for EUCAST guidelines implementation.

Importance: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI)., Objective: To compare the efficacy of standard-course and short-course therapy for children with UTI., Design, Setting, Participants: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials., Intervention: Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy)., Main Outcome Measures: The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms., Results: Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms., Conclusions and Relevance: In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01595529.

After the near absence of influenza and other respiratory viruses during the first 2 years of the COVID-19 pandemic, an increased activity of mainly influenza A(H3N2) was detected at the beginning of August 2022 in Greece on three islands. Of 33 cases with respiratory symptoms testing negative for SARS-CoV-2 with rapid antigen tests, 24 were positive for influenza: 20 as A(H3N2) subtype and four as A(H1N1)pdm09 subtype. Phylogenetic analysis of selected samples from both subtypes was performed and they fell into clusters within subclades that included the 2022/23 vaccine strains. Our data suggest that influenza can be transmitted even in the presence of another highly infectious pathogen, such as SARS-CoV-2, with a similar transmission mode. We highlight the need for implementing changes in the current influenza surveillance and suggest a move from seasonal to continuous surveillance, especially in areas with a high number of tourists. Year-round surveillance would allow for a timelier start of vaccination campaigns and antiviral drugs procurement processes.

In May 2022, for the first time, multiple cases of mpox were reported in several non-endemic countries. The first ever case of the disease in Greece was confirmed on 8 June 2022, and a total of 88 cases were reported in the country until the end of April 2023. A multidisciplinary response team was established by the Greek National Public Health Organization (EODY) to monitor and manage the situation. EODY's emergency response focused on enhanced surveillance, laboratory testing, contact tracing, medical countermeasures, and the education of health care providers and the public. Even though management of cases was considered successful and the risk from the disease was downgraded, sporadic cases continue to occur. Here, we provide epidemiological and laboratory features of the reported cases to depict the course of the disease notification rate. Our results suggest that measures for raising awareness as well as vaccination of high-risk groups of the population should be continued.

Background: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network., Objective: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design., Methods: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes., Results: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community., Conclusions: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials., (©Christos D Argyropoulos, Janina Leckler, Jon Salmanton-García, Marinos Constantinou, Alexandra Alexandrou, Sophia Themistocleous, Evgenia Noula, George Shiamakkides, Andria Nearchou, Fiona A Stewart, Kerstin Albus, Markela Koniordou, Ioannis Kopsidas, Orly Spivak, Margot Hellemans, Greet Hendrickx, Ruth Joanna Davis, Anna Maria Azzini, Paula Valle Simon, Antonio Javier Carcas-Sansuan, Helena Hervius Askling, Sirkka Vene, Jana Baranda Prellezo, Elena Álvarez-Barco, Alan J Macken, Romina Di Marzo, Catarina Luís, Ole F Olesen, Jesus A Frias Iniesta, Imre Barta, Krisztina Tóth, Murat Akova, Marc M J Bonten, Miriam Cohen-Kandli, Rebecca Jane Cox, Lenka Součková, Petr Husa, Ligita Jancoriene, Odile Launay, Jens Lundgren, Patrick Mallon, Charis Armeftis, Laura Marques, Pontus Naucler, Jordi Ochando, Evelina Tacconelli, Pierre van Damme, Theoklis Zaoutis, Sanne Hofstraat, Patricia Bruijning-Verhagen, Markus Zeitlinger, Oliver A Cornely, Zoi Dorothea Pana. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 03.04.2023.)

Objective: To assess the effect of new legislation on the dispensing of antimicrobials without prescription from pharmacies in Greece., Design: In-person survey., Setting: The study included 110 pharmacies in the greater Athens Metropolitan area., Methods: Volunteer collaborators visited 110 pharmacies in the greater Athens Metropolitan area in December 2021 and January 2022. They asked for either ciprofloxacin or amoxicillin-clavulanate acid (6:5 ratio) without providing a prescription, without simulating symptoms, and without offering justification or insisting. Fluoroquinolones have additional dispensing restrictions in Greece. Results were compared to a 2008 study. In 2020, legislation allowed the dispensing of antibiotics from pharmacies only with an electronic prescription, overriding the 1973 forbidding the dispensing of all medications without prescriptions., Results: All pharmacists refused to dispense ciprofloxacin without a prescription. Only 1 pharmacy dispensed amoxicillin-clavulanate without a prescription. Compared to the 2008 study, dispensing of amoxicillin-clavulanate without a prescription dropped from 100% in 2008 to 1% in 2021 and dispensing ciprofloxacin without a prescription dropped from 53% in 2008 to 0% in 2021., Conclusions: A new and enforced law that requires electronic prescribing led to a dramatic reduction of antibiotic dispensing without prescription compared to 12 years ago. Similar initiatives could help solve the problem of antibiotic consumption and resistance in Greece and elsewhere., Competing Interests: No author has any relevant conflicts of interest to declare related to this article., (© The Author(s) 2023.)

Our study aims to describe the global distribution and dispersal patterns of the SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from the CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, and BA.5* variants by geographic region. BA.1* increased in November 2021 in South Africa, with a similar increase across all continents in early December 2021. BA.1* did not reach 100% dominance in all continents. The spread of BA.2*, first described in South Africa, differed greatly by geographic region, in contrast to BA.1*, which followed a similar global expansion, firstly occurring in Asia and subsequently in Africa, Europe, Oceania, and North and South America. BA.4* and BA.5* followed a different pattern, where BA.4* reached high proportions (maximum 60%) only in Africa. BA.5* is currently, by Mid-August 2022, the dominant strain, reaching almost 100% across Europe, which is the first continent aside from Africa to show increasing proportions, and Asia, the Americas, and Oceania are following. The emergence of new variants depends mostly on their selective advantage, translated as enhanced transmissibility and ability to invade people with existing immunity. Describing these patterns is useful for a better understanding of the epidemiology of the VOCs' transmission and for generating hypotheses about the future of emerging variants.

A unified surveillance mechanism for hand hygiene and hospital-acquired infections for pediatric wards is lacking in Europe. We managed to setup such a mechanism in 9 pediatric intensive care units in 7 European countries, using World Health Organization's definitions and common methodology which allows for benchmarking among units and countries. Median hand hygiene compliance was found high 82.3% (interquartile range 71.6-94.5%), but gaps in practices were identified., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Early identification of COVID-19 cases has been vital for reducing transmission and enabling treatment. In Greece, in autumn 2021 when Delta was the predominant circulating variant, unvaccinated citizens had to be tested before attending activities, and self-testing was required twice a week for students (5−17 years). Here, we describe the time of diagnosis by age group and possible exposure to assess testing strategies (September to November 2021). Information on the presence of symptoms at the time of diagnosis was available for 69,298 cases; 24,855 (36%) were asymptomatic or tested the same day as onset (early diagnosis), 21,310 (31%) reported testing one day after, and 23,133 (33%) did so two or more days after the onset of symptoms. The median lag was 2 days (1−14). Early diagnosis significantly differed among age groups (p-value < 0.001) and was higher among children. For every one-year increase of age, the odds of an early diagnosis were reduced by 1%. Cases exposed during training activities or in settings such as accommodation centers and hospitals were more frequently diagnosed early. The percentage of persons having a positive self-test before a rapid test/PCR diagnosis ranged from 7% in the age group of 60 years and above to 86% in the age group of 5−17 years. The provision of self-tests in schools and increased testing in closed settings led to an earlier diagnosis and probably to a decreased transmission of the virus in the period during which Delta was the predominant variant in Greece. However, more effort is needed for early diagnosis of adults in the community, especially after the onset of symptoms.

Objective: We surveyed antimicrobials used in Greek pediatric hematology-oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients., Design: Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017., Intervention: In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated., Setting: Five of the 6 PHO units in Greece and the single pediatric BMT unit participated., Participants: Admitted children in each unit who received the first 15 new antibiotic courses each month., Results: Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children's hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P = .032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P = .008)., Conclusions: We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement., (© The Author(s) 2022.)

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. What is Known: • Neonates are frequently exposed to antibiotics for presumed EOS. • The Kaiser Permanente sepsis calculator can reduce antibiotic exposure in neonates.. What is New: • EOS calculator can be an effective antibiotic stewardship tool in a high prescribing country and can reduce invasive diagnostic procedures and mother-baby separation. • Incidence of EOS in Greece is higher compared to other European countries., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Aiming to the containment of the coronavirus disease 2019 (COVID-19) pandemic, governments worldwide have implemented a series of non-pharmaceutical interventions. Many of them and especially school closures have impacted the circulation of multiple airborne pathogens among children and adolescents. This study investigates the incidence of influenza and invasive meningococcal disease among children aged 0-14 years in Greece during the COVID-19 pandemic., Methods: Data regarding the number of influenza-like illness cases, influenza-related paediatric intensive care unit (PICU) admissions and invasive meningococcal disease cases among children 0-14 years old were obtained from the National Public Health Organization. The incidence of the two diseases during the COVID-19 pandemic period (2020/2021) was compared with that of the six preceding seasons (2014-2019)., Results: A notable decrease was observed in both influenza and invasive meningococcal disease cases during the period 2020/2021 compared with the years 2014-2019. The mean annual rate of influenza-like illness cases and influenza-related PICU admissions in children 0-14 years old has reduced by 66.9% and 100%, respectively, while the mean annual invasive meningococcal disease rate has declined by 70%. Both weekly influenza-like illness and monthly invasive meningococcal disease rates were significantly decreased., Conclusions: The activity of influenza and invasive meningococcal disease in the children and adolescents of Greece has decreased during the COVID-19 pandemic period. Reduced transmission is likely related to the public health measures that were implemented to control the pandemic. The value of these measures may have relevance to the future management of influenza or invasive meningococcal disease epidemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hospitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupation differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75-12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy.

Central line-associated bloodstream infections (CLABSIs) are the most frequent pediatric hospital-acquired infections and significantly impact outcomes. The aim of this study was to estimate the attributable mortality for CLABSIs in pediatric and neonatal patients in Greece. A retrospective matched-cohort study was performed, in two tertiary pediatric hospitals. Inpatients with a central line in neonatal and pediatric intensive care units (NICUs and PICUs), hematology/oncology units, and a bone marrow transplantation unit between June 2012 and June 2015 were eligible. Patients with confirmed CLABSI were enrolled on the day of the event and were matched (1:1) to non-CLABSI patients by hospital, hospitalization unit, and length of stay prior to study enrollment (188 children enrolled, 94 CLABSIs). Attributable mortality was estimated. During the study period, 22 patients with CLABSI and nine non-CLABSI patients died (23.4 vs. 9.6%, respectively, p  = 0.011), leading to an attributable mortality of 13.8% (95% confidence interval [CI] = 3.4-24.3%). Children in PICUs were more likely to die, presenting an attributable mortality of 20.2% (95% CI = - 1.4-41.8%), without reaching, however, statistical significance. After multiple logistic regression, patients with CLABSI were four times more likely to die (odds ratio [OR] = 4.29, 95% CI = 1.28-14.36, p  = 0.018). Survival analysis showed no difference in time to death after study enrollment between patients with CLABSI and non-CLABSI patients (log-rank p  = 0.137, overall median survival time = 7.8 months). Greek pediatric mortality rates are increased by the CLABSI occurrence, highlighting the importance of infection prevention strategies., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

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

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; MIC 50/90, 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.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

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.

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.

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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Bryan is a Canadian Agency for Drugs and Technologies in Health (Ottawa, ON, Canada) employee. The current work was unrelated to his employment and Canadian Agency for Drugs and Technologies in Health had no role in the funding, design, or oversight of the work reported; the other authors have indicated they have no potential conflicts of interest to disclose. ACKNOWLEDGEMENT: We thank Dr Joseph Chou, MD, PhD (Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA) for generating the birth anthropometric percentiles for the study population. Dr Chou did not receive any compensation for their assistance., (Copyright © 2021 by the American Academy of Pediatrics.)

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.

Fungal lung disease in the paediatric population occurs with distinct features in the immunocompetent, in immunocompromised patients and in people with cystic fibrosis. Pulmonary mycoses are the least prevalent in immunocompetent children, with the most common diseases being the endemic mycoses and Aspergillomas. Filamentous fungi such as Aspergillus and Scedosporium have been isolated with increased frequency in recent years from the respiratory secretions of individuals with cystic fibrosis. Undoubtedly, fungal respiratory infections are encountered with increased frequency and severity in patients with impaired immune systems, such as patients with malignancies, solid organ or bone marrow transplants and immunodeficiencies [1]., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Aim of the Work: Since December 2019, the world has been facing the coronavirus (COVID-19) pandemic crisis. The rapid and effortless spread of the virus has led the World Health Organization to adopt unprecedented large-scale preventive measures. Our aim is to investigate the impact of COVID-19 on the mental health of medical students, and to evaluate their awareness and aptitude for contributing to the fight against COVID-19 contagion., Methods: PubMed electronic database was employed for the research using the following terms: "medical students and COVID-19", "mental health of medical students and COVID-19", "knowledge of medical students and COVID-19", "preventive behavior of medical students and COVID-19"., Results: Twenty-one articles were included; ten assess the knowledge of medical students on COVID-19, seven present whether they demonstrate appropriate preventive behavior according to global guidelines, seven examine the impact of the pandemic on their mental health, five examine their role on the side of trained healthcare workers. Some articles combine more than one of the above mentioned domains., Conclusions: Medical students seem to demonstrate an adequate level of knowledge upon COVID-19 and implement proper strategies to prevent its spread. Further training is essential to improve some aspects in this field. Social media has proven to be the optimal source of information for medical students, which is incompatible with their future careers as doctors. The pandemic had a negative impact on medical students, expressed as fear regarding the virus spread; nevertheless, many have felt the need to assist healthcare systems under appropriate precautions.

Background: 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., Methods: Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression., Results: Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics., Conclusions: Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Antibiotic stewardship programs proved to be effective in improving prescribing appropriateness. This multicenter quasi-experimental study, aimed to assesses the stewardship impact on antibiotics prescribing in different semesters from 2014 to 2019 in three pediatric emergency departments (Center A, B, and C) in Italy. All consecutive patients diagnosed with acute otitis media or pharyngitis were evaluated for inclusion. Two different stewardship were adopted: for Center A and B, clinical pathways were implemented and disseminated, and yearly lectures were held, for Center C, only pathways were implemented. Broad-spectrum prescription rates decreased significantly by 80% for pharyngitis and 29.5 to 55.2% for otitis after the implementation. In Center C, rates gradually increased from the year after the implementation. Amoxicillin dosage adjusted to pharyngitis recommendations in Center C (53.7 vs. 51.6 mg/kg/die; p = 0.011) and otitis recommendations in Center A increasing from 50.0 to 75.0 mg/kg/die ( p < 0.001). Days of therapy in children < 24 months with otitis increased from 8.0 to 10.0 in Center A, while in older children decreased in Center A (8.0 vs. 7.0; p < 0.001) and Center B (10.0 vs. 8.0; p < 0.001). Clinical pathways combined with educational lectures is a feasible and sustainable program in reducing broad-spectrum antibiotic prescribing with stable rates over time.

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.

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

Background: Our objectives were to (1) characterize patient and clinical characteristics of adults hospitalized with meningitis; (2) describe meningitis hospitalization outcomes, including 30- and 90-day readmissions; and (3) determine whether clinical, patient, or index hospitalization characteristics are associated with readmission and readmission outcomes., Methods: This retrospective study of the 2014 National Readmissions Database extracted data on hospitalized adults with a principal diagnosis of meningitis and examined hospitalization outcomes using descriptive statistics. Logistic regression models were built to determine whether characteristics were associated with 30- or 90-day readmissions., Results: For the 30-day readmission analyses, 18,883 adults qualified. Meningitis hospitalizations commonly involved adults 25 to 54 years of age who were insured by private carriers. The readmission rates were 7.0% at 30 days and 11.4% at 90 days. Readmission was associated with greater comorbidity burden (2 conditions: adjusted odds ratio [AOR] = 1.60, range 1.24-2.08; 3 conditions: AOR = 1.92, range 1.43-2.58; 4+ conditions: AOR = 2.68, range 2.04-3.51 vs 0 or 1 condition), public insurance (Medicare: AOR = 1.85, range 1.30-2.62; Medicaid: AOR = 1.48, range 1.16-1.90 vs private insurance), and medical error (AOR = 1.43, range 1.07-1.91). Readmissions were most often for meningitis, septicemia, or medical complications., Conclusions: Readmission after hospitalization for meningitis is associated with both fixed and modifiable factors. More research is needed to determine which post-meningitis readmissions are preventable., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background-Appropriate perioperative antibiotic prophylaxis (PAP) is essential to prevent surgical site infections (SSIs) and to avoid antibiotics misuse. Aim-The aim of this study is to determine the effectiveness and long-term sustainability of an antimicrobial stewardship program (ASP), based on a clinical pathway (CP) and periodic education, to improve adherence to the guidelines for PAP in a tertiary care pediatric surgery center. Methods-We assessed the changes in PAP correctness and its effect on SSIs between the six months before and the 24 months after the implementation of ASP in the Pediatric Surgery Unit of the Department of Women's and Children's Health of Padova. The ASP was addressed to all surgeons and anesthesiologists of the Pediatric Surgery Unit. The primary outcome was appropriateness of PAP (agent, timing of the first dose, and duration). SSI rate was the secondary outcome. Results-1771 patients were included in the study and 676 received PAP. The overall correctness of the PAP, in terms of agent, timing, and duration, increased significantly after the CP implementation. What changed most was the PAP discontinuation within 24 h ( p < 0.001). Cefazolin was the most used antibiotic, with a significant increase in the post-intervention period ( p < 0.001) and with a reduction in the use of other broad-spectrum antibiotics. No variations in the incidence of SSIs were reported in the five periods ( p = 0.958). Conclusion-The implementation of an ASP based on CP and education is an effective and sustainable antimicrobial stewardship tool for improving the correct use of PAP.

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

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: Children, adolescents, and young adults with acute myeloid leukemia are at high risk of life-threatening invasive fungal disease with both yeasts and molds., Objective: To compare the efficacy of caspofungin vs fluconazole prophylaxis against proven or probable invasive fungal disease and invasive aspergillosis during neutropenia following acute myeloid leukemia chemotherapy., Design, Setting, and Participants: This multicenter, randomized, open-label, clinical trial enrolled patients aged 3 months to 30 years with newly diagnosed de novo, relapsed, or secondary acute myeloid leukemia being treated at 115 US and Canadian institutions (April 2011-November 2016; last follow-up June 30, 2018)., Interventions: Participants were randomly assigned during the first chemotherapy cycle to prophylaxis with caspofungin (n = 257) or fluconazole (n = 260). Prophylaxis was administered during the neutropenic period following each chemotherapy cycle., Main Outcomes and Measures: The primary outcome was proven or probable invasive fungal disease as adjudicated by blinded central review. Secondary outcomes were invasive aspergillosis, empirical antifungal therapy, and overall survival., Results: The second interim efficacy analysis and an unplanned futility analysis based on 394 patients appeared to have suggested futility, so the study was closed to accrual. Among the 517 participants who were randomized (median age, 9 years [range, 0-26 years]; 44% female), 508 (98%) completed the trial. The 23 proven or probable invasive fungal disease events (6 caspofungin vs 17 fluconazole) included 14 molds, 7 yeasts, and 2 fungi not further categorized. The 5-month cumulative incidence of proven or probable invasive fungal disease was 3.1% (95% CI, 1.3%-7.0%) in the caspofungin group vs 7.2% (95% CI, 4.4%-11.8%) in the fluconazole group (overall P = .03 by log-rank test) and for cumulative incidence of proven or probable invasive aspergillosis was 0.5% (95% CI, 0.1%-3.5%) with caspofungin vs 3.1% (95% CI, 1.4%-6.9%) with fluconazole (overall P = .046 by log-rank test). No statistically significant differences in empirical antifungal therapy (71.9% caspofungin vs 69.5% fluconazole, overall P = .78 by log-rank test) or 2-year overall survival (68.8% caspofungin vs 70.8% fluconazole, overall P = .66 by log-rank test) were observed. The most common toxicities were hypokalemia (22 caspofungin vs 13 fluconazole), respiratory failure (6 caspofungin vs 9 fluconazole), and elevated alanine transaminase (4 caspofungin vs 8 fluconazole)., Conclusions and Relevance: Among children, adolescents, and young adults with acute myeloid leukemia, prophylaxis with caspofungin compared with fluconazole resulted in significantly lower incidence of invasive fungal disease. The findings suggest that caspofungin may be considered for prophylaxis against invasive fungal disease, although study interpretation is limited by early termination due to an unplanned interim analysis that appeared to have suggested futility., Trial Registration: ClinicalTrials.gov Identifier: NCT01307579.

Background: There is ongoing debate about the best strategy to treat patients with tetralogy of Fallot who are symptomatic in the neonatal period., Objectives: The aim of this study was to compare the outcomes of complete versus staged surgery (i.e., initial palliative procedure for possible later complete repair)., Methods: A retrospective cohort study was performed using the Pediatric Health Information System database, including patients who underwent complete or staged tetralogy of Fallot repair prior to 30 days of age. The primary outcome was death during 2-year follow-up after the initial procedure. Inverse probability-weighted Cox and logistic regression models were used to examine the association between surgical approach group and mortality while accounting for patient- and hospital-level factors. Causal mediation analyses examined the role of intermediate variables., Results: A total of 2,363 patients were included (1,032 complete and 1,331 staged). There were 239 deaths. Complete neonatal repair was associated with a significantly higher risk for mortality during the 2-year follow-up period (hazard ratio: 1.51; 95% confidence interval: 1.05 to 2.06), between 7 and 30 days after the initial procedure (hazard ratio: 2.29; 95% confidence interval: 1.18 to 4.41), and during the initial hospital admission (odds ratio: 1.72; 95% confidence interval: 1.15 to 2.62). Post-operative cardiac complications were more common in the complete repair group and mediated the differences in 30-day and 2-year mortality., Conclusions: Complete surgical repair for neonates with tetralogy of Fallot is associated with a significantly higher risk for early and 2-year mortality compared with the staged approach, after accounting for patient and hospital characteristics. Post-operative cardiac complications mediated these findings., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sweden enjoys a favourable situation with regard to antimicrobial resistance. However, healthcare costs are expected to increase exponentially, along with increased morbidity and mortality, due to the emergence of resistant bacterial strains. Our aim was to design an antimicrobial stewardship programme suitable for Scandinavian settings. Methods: A quasi-experimental pre-post study was conducted in a Swedish paediatric emergency department, evaluating adherence to national guidelines for acute otitis media and acute tonsillitis. The programme consisted of educational outreach, decision support, feedback, and a minor reward upon reaching a pre-defined adherence rate. Results: The largest impact, significant for both diagnoses, was on the practice of refraining from antibiotic use when recommended. The other variables evaluated showed no significant improvement for either condition; however, in most cases, pre-interventional adherence was already high. Conclusions: This relatively easily implementable ASP intervention showed a significant effect on correctly refraining from the use of antibiotics. Previous interventions in Scandinavia either failed to accomplish this or have been more logistically difficult. The combination of education, decision support, email-based feedback and a minor reward, offers an alternative. Future research will be needed to assess whether the result is sustainable, as well as to identify additional barriers to the judicious use of antibiotics not addressed in this study.

Objective: To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece., Design: Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies., Setting: 16 NNUs in Greece participating in the neonIN infection surveillance network PATIENTS: Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics., Results: 459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). Coagulase-negative Staphylococci (80%) were the most common Gram-positive organisms causing LOS and Klebsiella spp (39%) the most common Gram-negative. Nearly half (45%) of the Klebsiella spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS., Conclusions: This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Central line-associated bloodstream infections (CLABSIs) are the most frequent pediatric hospital-acquired infections and are associated with significant morbidity and healthcare costs. The aim of our study was to determine the attributable length of stay (LOS) and cost for CLABSIs in pediatric patients in Greece, for which there is currently a paucity of data., Methods: A retrospective matched-cohort study was performed in two tertiary pediatric hospitals. Inpatients with a central line in neonatal and pediatric intensive care units, hematology/oncology units, and a bone marrow transplantation unit between June 2012 and June 2015 were eligible. Patients with confirmed CLABSI were enrolled on the day of the event and were matched (1:1) to patients without CLABSI (non-CLABSIs) by hospital, unit, and LOS prior to study enrollment (188 children enrolled, 94 CLABSIs). The primary outcome measure was the attributable LOS and cost. Baseline demographic and clinical characteristics were recorded. Attributable outcomes were calculated as the differences in estimates of outcomes between CLABSIs and non-CLABSIs, after adjustment for propensity score and potential confounders., Results: There were no differences between the two groups regarding their baseline characteristics. After adjustment for age, gender, matching characteristics, central line management after study enrollment, and propensity score, the mean LOS and cost were 57.5days and €31,302 in CLABSIs versus 36.6days and €17,788 in non-CLABSIs. Overall, a CLABSI was associated with a mean (95% CI) adjusted attributable LOS and cost of 21days (7.3-34.8) and €13,727 (5,758-21,695), respectively. No significant difference was detected in LOS and cost by hospitalization unit., Conclusions: CLABSIs were found to impose a significant economic burden in Greece, a finding that highlights the importance of implementing CLABSI prevention strategies., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART ® PneumoVir kit (GENOMICA, Spain). Α detailed questionnaire including demographics and medical history was also completed. Samples were processed in batches, results were communicated as soon as they became available. Children recruited in whom no virus was detected composed the no virus detected group. Viral prevalence was 38.4% in children presenting with respiratory illness. A single virus was found in 30.4%, with RSV being the most frequent. Viral coinfections were detected in 8%. Children with viral infection were more likely to be febrile upon enrollment and to present with lower respiratory signs/symptoms. They had longer duration of illness and they were more likely to receive antibiotics/antifungals. Only 22% of children with influenza received oseltamivir. Mortality was low (2.7%), however, pediatric intensive care unit (PICU) admission and death were correlated with virus detection. In our study mortality was low and PICU admission was related to virus identification. Further research is needed to clarify whether antibiotics in virus-proven infection are of value and underline the importance of oseltamivir's timely administration in influenza.

Purpose: This study aims to determine the effectiveness of an Antimicrobial Stewardship Program based on a Clinical Pathway (CP) to improve appropriateness in perioperative antibiotic prophylaxis (PAP)., Materials and Methods: This pre-post quasi-experimental study was conducted in a 12 month period (six months before and six months after CP implementation), in a tertiary Pediatric Surgical Centre. All patients from 1 month to 15 years of age receiving one or more surgical procedures were eligible for inclusion. PAP was defined appropriate according to clinical practice guidelines., Results: Seven hundred sixty-six children were included in the study, 394 in pre-intervention and 372 in post-intervention. After CP implementation, there was an increase in appropriate PAP administration, as well as in the selection of the appropriate antibiotic for prophylaxis, both for monotherapy (p = 0.02) and combination therapy (p = 0.004). Even the duration of prophylaxis decreased during the post-intervention period, with an increase of correct PAP discontinuation from 45.1 to 66.7% (p < 0.001). Despite the greater use of narrow-spectrum antibiotic for fewer days, there was no increase in treatment failures (10/394 (2.5%) pre vs 7/372 (1.9%) post, p = 0.54)., Conclusions: CPs can be a useful tool to improve the choice of antibiotic and the duration of PAP in pediatric patients., Competing Interests: All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee. Informed consent was obtained from all individual participants included in the study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Antibiotics are commonly prescribed for children with acute respiratory infections (ARIs). This study describes the distribution of ARI diagnoses and specifically quantifies antibiotic dispensing for bronchitis and upper respiratory infection (URI) by treatment setting and specialty., Methods: This retrospective, observational cross-sectional study used data from the HealthCore Integrated Research Environment containing claims from 14 commercial health plans for 2012 to 2014. Children (2-17 years) with first-episode ARI were identified by diagnosis of acute otitis media (AOM), sinusitis, pharyngitis, bronchitis or URI with no competing infections or chronic illnesses. Treatment setting was where diagnoses were made: primary care offices, urgent care centers (UCC), retail health clinics (RHCs) or emergency departments. Primary outcome measure was antibiotic prescription fills from pharmacies within 2 days of start of ARI episode., Results: For URI, the highest proportions in antibiotic dispensing were ordered by office-based or UCC family physicians (28% and 30%, respectively) and office-based or UCC nurse practitioners/physician assistants (30% and 29%, respectively). Across all settings and specialties, there was high proportion of antibiotic dispensing for bronchitis (75%). Overall, 48% of 544,531 children diagnosed with ARI filled antibiotics. Nurse practitioners/physician assistants in RHC made the most diagnoses of AOM (24%) and streptococcal pharyngitis (22%)., Conclusions: Outreach efforts to decrease antibiotic dispensing for URI can be focused on office-based and UCC family physicians and nurse practitioners/physician assistants. All specialties need widespread interventions to reduce antibiotic dispensing for bronchitis. RHC nurse practitioners/physician assistants can be targeted to reduce high proportion of AOM and streptococcal pharyngitis diagnoses.

Purpose: Urinary tract infections (UTIs) are common bacterial infections among children., Objective: To systematically review the antimicrobials used for febrile UTIs in paediatric clinical trials and meta-analyse the observed cure rates and reasons for treatment failure., Materials and Methods: We searched Medline, Embase and Cochrane central databases between January 1, 1990, and November 24, 2016, combining MeSH and free-text terms for: "urinary tract infections", AND "therapeutics", AND "clinical trials" in children (age range 0-18 years). Two independent reviewers assessed study quality and performed data extraction. The major outcome measures were clinical and microbiological cure rates according to different antibiotics., Results: We identified 2762 published studies and included 30 clinical trials investigating 3913 cases of paediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n = 2602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant UTIs have been tested in randomised clinical trials, mainly aminoglycosides. The average point cure rate of all investigational drugs was estimated to 95.3% (95% CI 93.5-96.9%). Among 3002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3002) had microbiological failure., Conclusions: We observed high treatment cure rates, regardless of the investigational drug chosen, the route of administration, duration and dosing. This suggests that future research should prioritise observational studies and clinical trials on children with multi-drug-resistant infections.

In this multicenter study, we identified an increased risk of 30-day mortality among hospitalized children with carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical cultures compared with those with carbapenem-susceptible Enterobacteriaceae. We additionally report significant variation in antibiotic treatment for children with CRE infections with infrequent use of combination therapy.

Background: Although Italian pediatric antimicrobial prescription rates are among the highest in Europe, little action has been taken to improve the appropriateness of antimicrobial prescriptions. The primary aim of this study was to assess changes in antibiotic prescription before and after acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis Clinical Pathway (CP) implementation; secondary aims were to compare treatment failures and to assess change in the total antibiotics costs before and after CP implementation., Methods: Pre-post quasi-experimental study comparing the 6-month period before CP implementation (baseline period: October 15, 2014, through April 15, 2015) to the 6 months after intervention (postintervention: October 15, 2015, through April 15, 2016)., Results: Two hundred ninety-five pre- and 278 postintervention emergency department visits were associated with AOM. After CP implementation, there was an increase in "wait and see" approach and a decrease in overall prescription of broad-spectrum antibiotics from 53.2% to 32.4% (P < 0.001). One hundred fifty-one pre- and 166 postimplementation clinic visits were associated with GAS pharyngitis, with a decrease in broad-spectrum prescription after CP implementation (46.4% vs. 6.6%; P < 0.001). For both conditions, no difference was found in treatment failure, and total antibiotics cost was significantly reduced after CP implementation, with a decrease especially in broad-spectrum antibiotics costs., Conclusions: A reduction in broad-spectrum antibiotic prescriptions and a reduction in the total cost of antibiotics for AOM and GAS pharyngitis along with an increase in "wait and see" prescribing for AOM indicate effectiveness of CP for antimicrobial stewardship in this setting.

Candidemia is the leading cause of invasive fungal infections in hospitalised children. The highest rates of candidemia have been recorded in neonates and infants <1 year of age. Candidemia is more frequent in neonates and young infants than in adults, and is associated with better clinical outcomes, but higher inpatient costs. Over the last 10 years, a declining trend has been noted in the incidence of paediatric candidemia in the US and elsewhere due to the hospital-wide implementation of central-line insertion and maintenance bundles that emphasise full sterile barrier precautions, chlorhexidine skin preparation during line insertion, meticulous site and tubing care, and daily discussion of catheter necessity. Additional interventions aiming at reducing gut-associated candidemia are required in immunocompromised and critically ill children., (© 2018 Blackwell Verlag GmbH.)