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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 Hos-pitals, 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 occupa-tion 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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. © Author(s) (or their employer(s)) 2022.

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]. © 2020

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. © 2021 Infection Control and Hospital Epidemiology. All rights reserved.

Background and aim of the work: Since December 2019, the world has been facing the coronavirus disease 2019 (COVID-19) pandemic. Medical students could not remain uninvolved. Our aim is to investigate the impact of COVID-19 on their mental health, and to evaluate their awareness and aptitude for contributing to the fight against COVID-19. Methods: An in-depth search of the literature was performed in Pubmed database, for studies investigating the preferred source of information about COVID-19, the knowledge on virus transmission, COVID-19 clinical symptoms and preventive measures against its spread, and the impact of COVID-19 on mental health among medical students. Their potential roles during the COVID-19 pandemic were also investigated. Results: Twenty studies were included. The majority of medical students prefer social media to acquire knowledge about COVID-19. They are adequately informed about COVID-19 transmission and symptoms, as well as preventive measures against COVID-19, although wear-ing a face-mask is not so popular among them. Their mental health is affected, mainly expressed as a fear of infection. Possible alternative roles of students during pandemic may be providing information to the public and tracing contacts of infected people. Conclusions: Medical students have an adequate level of knowledge upon COVID-19 and implement proper strategies to prevent its spread. Further training is essential to im-prove some aspects in this field. Despite the negative impact of COVID-19 on their mental health, they could assist healthcare systems under appropriate precautions. (www.actabiomedica.it). © Mattioli 1885.

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Objectives\ud The aim of this study was to describe antibiotic prescribing patterns and resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs).\ud \ud Methods\ud We evaluated antibiotic prescriptions and antibiograms for neonates, infants and older children with a UTI admitted to a general district hospital in central Greece. Data was collected retrospectively from the Paediatric Department’s Electronic Clinical Archive, covering a 5-year period. Patients were included based on clinical and microbiological criteria. Sensitivity to antimicrobials was determined using the Kirby-Bauer disk diffusion method.\ud \ud Results\ud Two hundred and thirty patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin-clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous treatments for febrile (mean 5.4 days; SD 1.45) and afebrile UTIs (mean 4.7 days; SD 1.34). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim-sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%). Lower resistance rates were identified for 3rd generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.3%) and amikacin (0.9%). Klebsiella sp. isolates were highly resistant to cefaclor (27.3%).\ud \ud Conclusion\ud We observed high prescribing rates for amikacin and penicillins (+/-beta lactamase inhibitors) and prolonged intravenous treatments. E.coli appeared to be highly resistant to ampicillin, whilst 3rd generation cephalosporins exhibited higher in vitro efficacy. The establishment of antimicrobial stewardship programs and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs.

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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: The aim of this study was to describe antibiotic prescribing patterns and antimicrobial resistance rates in hospitalised children with febrile and afebrile urinary tract infections (UTIs). Methods: Antibiotic prescriptions and antibiograms for neonates, infants and older children with UTI admitted to a general district hospital in Central Greece were evaluated. Data covering a 5-year period were collected retrospectively from the Paediatric Department's Electronic Clinical Archive. Patients were included based on clinical and microbiological criteria. Antimicrobial susceptibility was determined by the Kirby–Bauer disk diffusion method. Results: A total of 230 patients were included in the study. Among 459 prescriptions identified, amikacin (31.2%) was the most common antibiotic prescribed in this population, followed by amoxicillin/clavulanic acid (17.4%) and ampicillin (13.5%). Children received prolonged intravenous (i.v.) treatments for febrile (mean ± S.D., 5.4 ± 1.45 days) and afebrile UTIs (mean ± S.D., 4.4 ± 1.64 days). A total of 236 pathogens were isolated. The main causative organism was Escherichia coli (79.2%) with high reported resistance rates to ampicillin (42.0%), trimethoprim/sulfamethoxazole (26.5%) and amoxicillin/clavulanic acid (12.2%); lower resistance rates were identified for third-generation cephalosporins (1.7%), nitrofurantoin (2.3%), ciprofloxacin (1.4%) and amikacin (0.9%). Klebsiella spp. isolates were highly resistant to cefaclor (27.3%). Conclusion: High prescribing rates for amikacin and penicillins (± β-lactamase inhibitors) and prolonged i.v. treatments were observed. Escherichia coli was highly resistant to ampicillin, whilst third-generation cephalosporins exhibited greater in vitro efficacy. Establishment of antimicrobial stewardship programmes and regular monitoring of antimicrobial resistance could help to minimise inappropriate prescribing for UTIs. © 2019 International Society for Chemotherapy of Infection and Cancer

Background: 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 (EnprEMA), in collaboration with the Paediatric European Network for Treatments of AIDS – Infectious Diseases (PENTA-ID) network (www.penta-id.org), recently developed a Working Group (WG) on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. Objectives: 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 (I) 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; (II) key components of safety that should be reported in paediatric antibiotic CTs; (III) standardised sample sizes for safety studies. Results: 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. Conclusion: 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 clinical trials networks and regulators.

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.

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide. Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H). Results: Of 17693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America). Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children., peer-reviewed

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 57.5 days and €31,302 in CLABSIs versus 36.6 days and €17,788 in non-CLABSIs. Overall, a CLABSI was associated with a mean (95% CI) adjusted attributable LOS and cost of 21 days (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. © 2018 The Authors

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. © 2019 Elsevier Ltd

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. © 2019, © 2019 Taylor & Francis Group, LLC.

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. © 2019 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC.

ObjectiveTo assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics.DesignParticipating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children.Results84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy.ConclusionsComprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.

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. © 2018, Springer Nature Switzerland AG.

Context: Urinary tract infections (UTIs) represent a common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist. Objective: To assess the criteria used for patients selection and the efficacy endpoints in febrile pediatric UTI CTs. Data Sources: Medline, Embase, Cochrane central databases and ClinicalTrials.gov between January 1, 1990, and November 24, 2016. Study Selection: We combined MeSH and free-text terms for: “urinary tract infections”, AND “therapeutics”, AND “clinical trials” in children (0–18 years), identifying 3,086 papers. Data Extraction: Two independent reviewers assessed study quality and performed data extraction. Results: Forty CTs investigating 4,381 cases of pediatric febrile UTIs were included. Positive urine culture and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria and colonies thresholds were highly variable. Clinical and microbiological endpoints were assessed in 88% and 93% of the studies, respectively. Timing for endpoints assessment was highly variable, and only 3 studies (17%), out of the 18 performed after the Food and Drug Administration 1998 guidance publication, assessed primary and secondary endpoints consistently with this guidance. Limitations: Mixed population of healthy children and with underlying condition. Six trials studied a subgroup of patients with afebrile UTI. Conclusions: We observed a wide variability in the microbiological inclusion criteria and the timing for endpoints assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is required.

Objectives: Previously, web-based tools for cross-sectional antimicrobial point prevalence surveys (PPSs) have been used in adults to develop indicators of quality improvement. We aimed to determine the feasibility of developing similar quality indicators of improved antimicrobial prescribing focusing specifically on hospitalized neonates and children worldwide. Methods: A standardized antimicrobial PPS method was employed. Included were all inpatient children and neonates receiving an antimicrobial at 8:00 am on the day of the PPS. Denominators included the total number of inpatients. A web-based application was used for data entry, validation and reporting. We analysed 2012 data from 226 hospitals (H) in 41 countries (C) from Europe (174H; 24C), Africa (6H; 4C), Asia (25H; 8C), Australia (6H), Latin America (11H; 3C) and North America (4H). Results: Of 17 693 admissions, 6499 (36.7%) inpatients received at least one antimicrobial, but this varied considerably between wards and regions. Potential indicators included very high broad-spectrum antibiotic prescribing in children of mainly ceftriaxone (ranked first in Eastern Europe, 31.3%; Asia, 13.0%; Southern Europe, 9.8%), cefepime (ranked third in North America, 7.8%) and meropenem (ranked first in Latin America, 13.1%). The survey identified worryingly high use of critically important antibiotics for hospital-acquired infections in neonates (34.9%; range from 14.2% in Africa to 68.0% in Latin America) compared with children (28.3%; range from 14.5% in Africa to 48.9% in Latin America). Parenteral administration was very common among children in Asia (88%), Latin America (81%) and Europe (67%). Documentation of the reasons for antibiotic prescribing was lowest in Latin America (52%). Prolonged surgical prophylaxis rates ranged from 78% (Europe) to 84% (Latin America). Conclusions: Simple web-based PPS tools provide a feasible method to identify areas for improvement of antibiotic use, to set benchmarks and to monitor future interventions in hospitalized neonates and children. To our knowledge, this study has derived the first global quality indicators for antibiotic use in hospitalized neonates and children. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Background/Purpose Appropriate antimicrobial prophylaxis (PAP) prevents surgical site infections (SSI). The aim of this study was to evaluate the effectiveness of an educational intervention to improve adherence to PAP guidelines in pediatric patients. Methods A three-phase prospective study with a pre-post design was conducted from April 2013 to December 2014. All patients who underwent one or more surgical procedures were enrolled. A modified Centers for Disease Control's (CDC) Denominator for Procedure form was used to collect clinical and PAP data. The educational intervention was targeted at all pediatric surgeons in the department. Outcomes assessed were the appropriateness of the agent selected for PAP (according to international guidelines) and appropriate termination of PAP within 24 h of surgery completion. SSI rates were calculated before and after the intervention. Results During the study period 889 children were enrolled (219 in the preintervention and 670 in the postintervention period). The percentage of patients receiving appropriate PAP improved from 6.2% to 77.1% after the educational intervention (p

Objective: To assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics. Design: Participating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children. Results: 84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy. Conclusions: Comprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.

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.

BackgroundMucormycosis 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.MethodsFrom 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). The author group based in 17 time zones, relied on electronic media including video tutorial on methodology, and central document repository with several daily updates.FindingsSigns and symptoms of mucormycosis depend on organ patterns and underlying conditions. 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.InterpretationManagement 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.