Search

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients' group compared to the healthy control group ( p < 0.001, in all comparisons). SuPAR levels at baseline were associated with the m-EASIX scores calculated at the same time point ( p = 0.020), while suPAR and GDF-15 concentrations were correlated with EASIX scores at day 14 post-infusion ( p < 0.001 in both comparisons). Moreover, sC5b-9 levels were correlated with the s-EASIX scores at infusion ( p = 0.008) and the EASIX scores at day 14 ( p = 0.005). In our study, sC5b9, suPAR, and GDF-15 levels were found to reflect endothelial injury in CAR-T cell recipients.

Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT. Results: In terms of severe aGvHD, most of the patients (19/28) responded to ECP treatment, while the five-year overall survival (OS) was 34%. After adjustment for several confounder factors, the reduction in immunosuppression ( p = 0.026) and number of ECP sessions ( p < 0.001) were associated with improved OS. Regarding chronic GvHD, only 19 patients failed to respond to ECP treatment; though significantly lower rates of response were presented in patients with visceral involvement ( p = 0.037) and earlier post-transplant GVHD diagnosis ( p = 0.001). Over a follow-up period of 45.2 [interquartile range (IQR): 5.6-345.1] months, the 5-year cumulative incidence (CI) of cGvHD-related mortality was 21.2% and was significantly reduced in patients with ECP response ( p < 0.001), while the 5-year OS was 65.3%. Conclusions: Our results confirm the safety and efficacy of ECP in patients with GvHD and provide sufficient data for further investigation and the best combination drugs needed such that GvHD will not be the major barrier of allo-HCT in the near future.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition that may occur following SARS-CoV-2 infection. This retrospective, descriptive study of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) in 12 tertiary care centers from 3/11/2020 to 12/31/2021. Demographics, clinical and laboratory characteristics, treatment and outcomes are described. Among 145 patients (95 males, median age 8.2 years) included, 123 met the WHO criteria for MIS-C, while 112 (77%) had serological evidence of SARS-CoV-2 infection. Fever was present in 99%, gastrointestinal symptoms in 77%, mucocutaneous involvement in 68% and respiratory symptoms in 28%. Fifty-five patients (38%) developed myocarditis, 29 (20%) pericarditis and 19 (13%) coronary aneurysms. Among the above cases 11/55 (20%), 1/29 (3.4%) and 5/19 (26.3%), respectively, cardiac complications had not fully resolved at discharge. Underlying comorbidities were reported in 18%. Median CRP value was 155 mg/l, ferritin 535 ng/ml, PCT 1.6 ng/ml and WBC 14.2 × 10 9 /mm 3 . Most patients had elevated troponin (41.3%) and/or NT-pro-BNP (49.6%). Intravenous immunoglobulin plus corticosteroids were used in 117/145 (80.6%), monotherapy with IVIG alone in 13/145 (8.9%) and with corticosteroids alone in 2/145 (1.3%). Anti-IL1 treatment was added in 15 patients (10.3%). Thirty-three patients (23%) were admitted to the PICU, 14% developed shock and 1 required ECMO. Mortality rate was 0.68%. The incidence of MIS-C was estimated at 0.69/1000 SARS-CoV-2 infections. Patients who presented with shock had higher levels of NT-pro-BNP compared to those who did not (p < 0.001). Acute kidney injury and/or myocarditis were associated with higher risk of developing shock., Conclusion: MIS-C is a novel, infrequent but serious disease entity. Cardiac manifestations included myocarditis and pericarditis, which resolved in most patients before discharge. Timely initiation of immunomodulatory therapy was shown to be effective. NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. Further research is required to elucidate the pathogenesis, risk factors and optimal management, and long-term outcomes of this clinical entity., What Is Known: • MIS-C is an infrequent but serious disease entity. • Patients with MIS-C present with multi-organ dysfunction, primarily involving the gastrointestinal and cardiovascular systems., What Is New: • NT-pro-BNP levels may provide a better prediction and monitoring of the disease course. • Acute kidney injury and/or myocarditis were associated with higher risk of developing shock., (© 2024. The Author(s).)

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) and graft-versus-host disease (GvHD) represent life-threatening syndromes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both conditions, endothelial dysfunction is a common denominator, and development of relevant biomarkers is of high importance for both diagnosis and prognosis. Despite the fact that soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings, their role in HSCT-related complications remains unexplored. In this context, we used immunoenzymatic methods to measure suPAR and GDF-15 levels in HSCT-TMA, acute and/or chronic GVHD, control HSCT recipients, and apparently healthy individuals of similar age and gender. We found considerably greater SuPAR and GDF-15 levels in HSCT-TMA and GVHD patients compared to allo-HSCT and healthy patients. Both GDF-15 and suPAR concentrations were linked to EASIX at day 100 and last follow-up. SuPAR was associated with creatinine and platelets at day 100 and last follow-up, while GDF-15 was associated only with platelets, suggesting that laboratory values do not drive EASIX. SuPAR, but not GDF-15, was related to soluble C5b-9 levels, a sign of increased HSCT-TMA risk. Our study shows for the first time that suPAR and GDF-15 indicate endothelial damage in allo-HSCT recipients. Rigorous validation of these biomarkers in many cohorts may provide utility for their usefulness in identifying and stratifying allo-HSCT recipients with endothelial cell impairment.

The purpose of this study was to investigate knowledge, principles, and practices concerning the management of children with febrile seizures among pediatricians in Greece. A cross-sectional study was performed across Greece. Pediatricians completed an anonymous and voluntary 11-item questionnaire about their knowledge, attitudes, and practices with respect to the management of febrile seizures; the survey also collected demographic data. It was first administered in paper form in October 2017. This was followed by an online survey performed between June and August of 2018 and publicized by medical boards across Greece. Descriptive statistics and comparisons between groups were conducted with the significance level set at p ≤ 0.05. We recorded 457 responses. Pediatricians admitted to modifying their advice to the parents of children with febrile seizures by suggesting more "aggressive" fever management at low temperatures or systematically (63%), referral to a specialist after any episode of febrile seizures (63%), or hospitalization in a subsequent episode (67%), even though 72% admitted these practices were of no efficacy. Almost one in three pediatricians (28%) believed aggressive management of fever could delay the onset of febrile seizures; increasing age was associated with this perception. A minority (28%) would make parents aware of febrile seizures before a first episode regardless of family history; 38% would do so in the event of family history., Conclusions: Several pediatricians in Greece use outdated and ineffective practices for the management of febrile seizures, despite the availability of updated evidence-based guidelines. Further training of practitioners is needed to bridge this gap., What Is Known: •Aggressive management of fever at low temperatures with antipyretics, referral to a neurologist, and hospitalization are not supported by evidence or recent guidelines on childhood febrile seizures. •Febrile seizures are especially disturbing to uninformed parents, who may be inclined to pursue aggressive but ineffective treatments as a result., What Is New: •Pediatricians in Greece use non-evidence-based practices for the management of febrile seizures, even when they are aware that these practices are not effective. •Older age increases the likelihood that a pediatrician will pursue guideline non-compliant practices in Greece. At the same time, physicians with over 20 years of experience are more likely to inform parents in advance about febrile seizures., (© 2023. The Author(s).)

Objectives: Mass vaccination is the most effective strategy for controlling the COVID-19 pandemic. This study aimed to evaluate the 6-month immunogenicity after BNT162b2-COVID-19 vaccination in adolescents with JIA on TNFi treatment., Methods: This single-centre study included adolescents with JIA treated with TNFi for at least 18 months. Patients received two doses of COVID-19 vaccine (Pfizer-BioNTech) from 15 April to 15 May 2021. Quantitative measurement of IgG antibodies to SARS-CoV-2-spike-protein-1 was performed at 1, 3 and 6 months post-vaccination., Results: Overall, 21 adolescents with JIA in clinical remission at the time of vaccinations were enrolled. None of them discontinued TNFi/MTX treatment at the time of vaccine administration or during the follow-up period. All patients developed a sustained humoral response against SARS-CoV-2 at 1 and 3 months after vaccination (P < 0.05). The antibody levels decreased significantly at 6 months post-vaccination (P < 0.01). The type of JIA did not reveal any differences in the humoral response at 3 (P = 0.894) or 6 months post-vaccination (P = 0.72). No difference was detected upon comparison of the immunogenicity between the different treatment arms (adalimumab vs etanercept) at 3 (P = 0.387) and 6 months (P = 0.526), or TNFi monotherapy vs combined therapy (TNFi plus methotrexate) at 3 (P = 0.623) and 6 months (P = 0.885)., Conclusions: Although mRNA vaccines develop satisfactory immunogenicity at 1 month and 3 months post-vaccination in adolescents with JIA on TNFi, SARS-CoV-2 antibody titres decrease significantly overtime, remaining at lower levels at 6 months. Further collaborative studies are required to determine long-term immunogenicity, real duration of immune protection and the need for a booster vaccine dose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this nationwide retrospective study, a substantial decline in the incidence of multisystem inflammatory syndrome in children over 3 successive pandemic waves characterized by different severe acute respiratory syndrome coronavirus 2 variants was documented-from 3.4 of 1000 to 1.1 of 1000 and finally to 0.25 of 1000 confirmed severe acute respiratory syndrome coronavirus 2 positive cases (P < 0.0001), respectively, whereas clinical findings and severity did not significantly vary., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

This study aims to describe the clinical characteristics and outcome of 92 infants (aged <12 months) with community-acquired coronavirus disease 2019 (COVID-19) between March, 2020 and June, 2021 at a single center in Athens. Infants with COVID-19 developed mild disease (89, 96.7%), and were infected mostly by their household contacts (74, 80.4%). Disease complications were rare, indicating that hospitalization is the result of low threshold for admission rather than disease severity.

Aim: This study aims to construct and validate a new score for diagnosis of complicated appendicitis in children, complicated appendicitis pediatric score (CoAPS), to guide residents' clinical decision-making on choosing the correct patients for immediate surgery, reducing the emergency negative surgeries., Methods: This prospective observational study enrolled two cohorts of patients 5-15 years old. Four hundred and seven consecutive patients were enrolled for the derivation cohort. Demographic data, clinical features, and histopathology data were collected. The outcome measure was the histological diagnosis of gangrenous appendicitis with or without perforation. The score was next validated in a separate cohort of 312 consecutive patients who were classified according to their risk of complicated appendicitis. The diagnostic performance of the score and the potential for the risk stratification to select patients for diagnostic imaging, emergency operative management, and reduce emergency negative operation rates were quantified., Results: A positive "jumping up" test, vomiting, white blood cell >13.5 × 10^3/ml, lymphocytes <18%, and C-reactive protein >50 mg/dl were independent predictors for complicated appendicitis. The final prediction model exhibited an area under the curve of 0.890 (95% confidence interval: 0.859-0.922). The low-risk group demonstrated high sensitivity (90.4%) for complicated appendicitis, while scores 6 or more were very specific (95%) for the disorder. Describing the potential utility of the score, emergency ultrasound imaging would have been postponed in 14.5% of patients ( P = 0.0016), and emergency negative explorations would have been cut by 87%., Conclusion: The CoAPS score could guide residents in emergency management of children with complicated appendicitis reducing hospitalizations and urgent surgeries., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Indian Association of Pediatric Surgeons.)

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: Identifying potential predictive factors for the type of bacteremia (Gram-negative vs. Gram-positive) in children with cancer would be crucial for the timely selection of the appropriate empiric antibiotic treatment., Materials and Methods: Demographic, clinical, and laboratory characteristics of children with cancer and a bacterial bloodstream infection (BSI) (February 1, 2011 to February 28, 2018) in a tertiary pediatric oncology department were retrospectively examined and were correlated with the type of isolated bacteria., Results: Among 224 monomicrobial bacterial BSI episodes, Gram-negative and Gram-positive bacteria were isolated in 110 and 114 episodes, respectively. Gram-negative bacteria were isolated significantly more frequently in girls (Gram-negative/Gram-positive ratio 1.7:1) versus boys (Gram-negative/Gram-positive ratio 0.72:1), P=0.002, in patients with previous BSI episodes (1.4:1) versus those without (0.8:1), P=0.042, and in children with hematologic malignancy (1.3:1) versus those who suffered from solid tumors (0.52:1), P=0.003. Gram-negative BSI episodes were more frequently correlated with a lower count of leukocytes, P=0.009, neutrophils, P=0.009 and platelets, P=0.002, but with significantly higher C-reactive protein (CRP) levels, P=0.049. Female sex, hematologic malignancy, and higher CRP levels remained independent risk factors for Gram-negative BSI in the multivariate analysis. Among neutropenic patients, boys with solid tumors and a recent central venous catheter placement appear to be at increased risk for Gram-positive BSI in the multivariate analysis., Conclusions: Although Gram-negative and Gram-positive BSIs are close to balance in children with cancer, Gram-negative bacteria are more likely to be isolated in girls, children with hematologic malignancies and those with higher CRP level at admission. In contrast, neutropenic boys with solid tumors and a recently placed central venous catheter may be at increased risk for Gram-positive BSI indicating probably the need for initially adding antibiotics targeting Gram-positive bacteria., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rapid antigen detection (RAD) tests for the detection of SARS-CoV-2 are simpler, faster, and less expensive than the reverse-transcription polymerase chain reaction (RT-PCR) that is currently considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19). The objective of this study was to determine the performance of the PANBIO COVID-19 Ag RAD (Abbott) test, a lateral flow immunoassay that detects the nucleocapsid protein, using as a reference RT-PCR method the Cobas®8800 System (Roche Diagnostics). This prospective study was conducted in a tertiary Children's Hospital and included individuals aged ≤16 years with COVID-19-related symptoms or epidemiological criteria for COVID-19. Two nasopharyngeal samples were collected to perform the PANBIO RAD test and RT-PCR. Of 744 children included, 51 (6.86%) had a positive RT-PCR result. The RAD test detected 42 of 51 PCR-positive children while there were no false-positive results. The overall sensitivity and specificity were 82.35% (95% CI, 71.9%-92.8%) and 100%, respectively. Sensitivity was >95% in symptomatic children. The assay performed poorly in asymptomatically infected children. In agreement with previous studies in adults, the PANBIO RAD test can be useful in screening for COVID-19 in children admitted with symptoms suggestive of the disease, especially in the first days of the illness., (© 2021 Wiley Periodicals LLC.)

Children and adolescents with severe acute respiratory syndrome coronavirus 2 infection usually have a milder illness, lower mortality rates and may manifest different clinical entities compared with adults. Acute effusive pericarditis is a rare clinical manifestation in patients with COVID-19, especially among those without concurrent pulmonary disease or myocardial injury. We present 2 cases of acute pericarditis, in the absence of initial respiratory or other symptoms, in adolescents with COVID-19., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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

Background: 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.

The Bacille Calmette-Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23-0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15-0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13-4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27-9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case.

We evaluate a new clinical test, jumping up (J-up) test, to diagnose easier appendicitis in children. A total of 407 patients, aged 5 to16 years, with right lower quadrant abdominal pain were asked to jump rising both hands and trying to reach a toy hanging down from the ceiling of the examination room. Bieri pediatric Face Pain Scale was used for recording the pain response. J-up test has sensitivity of 87% and specificity of 70%. A positive J-up test combined with leukocytosis (white blood cells count >12 000/mm 3 ), neutrophilia >75%, neutrophil/lymphocyte >2, and C-reactive protein >5 mg/dL, achieved a posttest probability of appendicitis of 85%. A negative J-up test combined with the aforementioned blood markers within normal range had a posttest probability for non-appendicitis of 92%. J-up test is a reliable clinical test, which could be used even by an inexperienced doctor. Combined with classical blood markers, it could successfully predict which child is in urgent need or not of surgery., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

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: Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children., Aim: To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs)., Methods: Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms., Findings: A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems., Conclusion: Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions., (Copyright © 2018 The Healthcare Infection Society. All rights reserved.)

We report the case of an 11-year-old immunocompetent patient presenting with a 2-week history of upper back pain, diagnosed with thoracic vertebral osteomyelitis and a paraspinal abscess caused by Bartonella henselae. He was treated with gentamicin and doxycycline followed by oral rifampicin and doxycycline with favorable outcome.

Background: Visceral leishmaniasis (VL) remains an important public health problem in endemic regions. Current antileishmanial agents share several limitations including potentially serious side effects and the risk of clinical failure., Objectives: Aim of this study was to examine the effectiveness and safety of short-course liposomal amphotericin B (L-AmB) regimens in the treatment of childhood VL in our area., Methods: The cases of 43 VL patients (20 males; 23 females; mean age: 4.6 years) treated at a tertiary children's hospital over an 11-year period were retrospectively reviewed. Diagnosis was confirmed with identification of Leishmania spp. in bone marrow samples and/or a positive serologic test. All patients were treated with 5 different L-AmB regimens at a dose of 18-22 mg/kg., Results: Initial response to treatment was attained in all patients (100%), while definitive cure at 6 months was achieved in 98% of patients. Adverse effects were recorded in 14 children and consisted mostly of infusion reactions and electrolyte disorders. Self-limiting nephrotoxicity was observed in 3 patients including a 12-year-old girl in whom acute kidney injury was developed. In addition, ventricular arrhythmias developed in a 13-year-old boy necessitating drug discontinuation. Although side effects were more frequent with the 2-day regimen, the difference with regard to toxicity between dosing regimens was not significant., Conclusions: Short-course L-AmB regimens are effective and safe for the treatment of childhood VL in our area. Our findings suggest that large L-AmB doses can possibly account for a higher rate of adverse events including nephrotoxicity.

Skin and soft tissue infections (SSTIs) caused by mupirocin-resistant Staphylococcus aureus strains have recently increased in number in our settings. We sought to evaluate the characteristics of these cases over a 43-month period. Data for all community-acquired staphylococcal infections caused by mupirocin-resistant strains were retrospectively reviewed. Genes encoding products producing high-level resistance (HLR) to mupirocin ( mupA ), fusidic acid resistance ( fusB ), resistance to macrolides and lincosamides ( ermC and ermA ), Panton-Valentine leukocidin (PVL) ( lukS/lukF -PV), exfoliative toxins ( eta and etb ), and fibronectin binding protein A ( fnbA ) were investigated by PCRs in 102 selected preserved strains. Genotyping was performed by SCC mec and agr typing, whereas clonality was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 437 cases among 2,137 staphylococcal infections were recorded in 2013 to 2016; they were all SSTIs with the exception of 1 case of primary bacteremia. Impetigo was the predominant clinical entity (371 cases [84.9%]), followed by staphylococcal scalded skin syndrome (21 cases [4.8%]), and there were no abscesses. The number of infections detected annually increased during the study years. All except 3 isolates were methicillin susceptible. The rates of HLR to mupirocin and constitutive resistance to clindamycin were 99% and 20.1%, respectively. Among the 102 tested strains, 100 (98%) were mupA positive and 97 (95%) were fusB positive, 26/27 clindamycin-resistant strains (96.3%) were ermA positive, 83 strains (81.4%) were lukS/lukF positive, 95 (93%) carried both eta and etb genes, and 99 (97%) were fnbA positive. Genotyping of methicillin-sensitive S. aureus (MSSA) strains revealed that 96/99 (96.7%) belonged to one main pulsotype, pulsotype 1, classified as sequence type 121 (ST121). The emergence of a single MSSA clone (ST121) causing impetigo was documented. Resistance to topical antimicrobials and a rich toxinogenic profile confer to this clone adaptability for spread in the community., (Copyright © 2017 American Society for Microbiology.)

Objectives: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV., Methods: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events., Results: 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated., Conclusions: Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

We analyzed the use of low-dose alemtuzumab in a cohort of 158 consecutive patients who underwent allogeneic PBSC transplantation. Patients with high-risk acute leukemia were prospectively screened for prophylactic donor lymphocyte infusion (pDLI). Lymphocytes were administered repeatedly at low and non-escalating doses (0.5-1 × 10 6 /kg). Low-dose alemtuzumab was effective in prevention of acute GvHD after sibling or well-matched unrelated transplantation, whereas a more intensified approach was needed after mismatched transplantation. The cumulative incidence of chronic moderate/severe chronic-GvHD (cGvHD) was 15.6%. In total, 63 high-risk leukemia patients were eligible for pDLI. Only 1 out of the 39 pDLI recipients relapsed as compared with 7 out of the 24 recipients, who did not receive pDLI due to logistical hurdles. In multivariate analysis, the use of adjuvant lymphocyte therapy was significantly associated with reduced incidence of relapse and improved disease-free survival. In summary, low-dose alemtuzumab confers to a low cGvHD incidence and the administration of pDLIs in this context is very likely to reduce relapse risk in high risk leukemia patients. This is translated in an estimated 5-year probability of GvHD-free and relapse-free survival of 43.3% for the 136 leukemia patients.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To assess interferon-gamma inducible protein 10 (IP-10) as a diagnostic marker for tuberculous infection in children, particularly in relation to its differential diagnostic performance in young children., Design and Results: A case-control study was conducted among 161 children and adolescents (mean age 6.3 years ± standard deviation 1.7; males n = 79, 49%). Fifty-four (33.5%) had active TB, 53 (33%) had latent tuberculous infection (LTBI), and 54 (33.5%) were non-LTBI controls. Unstimulated IP-10 levels did not differ between groups (P > 0.05 for all comparisons). TB-specific antigen stimulated IP-10 levels were more profoundly increased in infected groups than in controls (P < 0.001 for all comparisons). None of the IP-10-based diagnostic indexes demonstrated the ability to discriminate active disease from LTBI. A value of IP-10 ⩾ 1222 pg/ml had 83.3% sensitivity, 79.6% specificity, 80.4% positive predictive value and 82.7% negative predictive value for the diagnosis of LTBI. IP-10 based indexes demonstrated a trend towards better performance in the population group aged <5 years., Conclusion: The IP-10 assay could be useful in improving the diagnosis of LTBI in patients aged <5 years in combination with existing interferon-gamma release assays.

Objectives: The objectives of this study were to provide a nationally representative analysis of antibiotic prescribing in outpatient paediatrics and to assess overall and class-specific antibiotic costs in Greece., Methods: Data on antibiotic prescriptions for patients aged ≤19 years old between July 2010 and June 2013 in Greece were extracted from the IMS Health Xponent database. Antibiotics were grouped into narrow- and broad-spectrum agents. The number of prescribed antibiotics and census denominators were used to calculate prescribing rates. The total costs associated with prescribed antibiotics were calculated., Results: More than 7 million antibiotics were prescribed during the study period, with an annual rate of 1100 antibiotics/1000 persons. Prescribing rates were higher among children aged <10 years old. Acute respiratory tract infections (ARTIs) accounted for 80% of prescribed antibiotics, with acute otitis media (22.3%), acute tonsillitis (19.5%) and acute bronchitis/bronchiolitis (13.9%) being the most common clinical diagnoses. Cephalosporins (32.9%), penicillins (32.3%) and macrolides (32.1%) were the most commonly prescribed antibiotic classes. The majority (90.4%) of antibiotics were broad spectrum. Antibiotic expenditures totalled ∼€50 million., Conclusions: Broad-spectrum antibiotic prescribing is common in outpatient paediatric patients. These data provide important targets to inform the development of an outpatient antimicrobial stewardship programme targeting specific practices, providers and conditions., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Hand hygiene (HH) is the most effective way to prevent health care-associated infections and the spread of antimicrobial-resistant pathogens. The aim of our study was to assess the existing HH resources and current HH practices at 2 hospitals in Athens, Greece., Methods: Observational HH data and an inventory of HH resources were collected from 13 wards including medical/surgical, oncology/transplant and intensive care units, during 65, 1-hour observations periods., Results: A total of 1271 HH opportunities were observed during the study period, including 944 of Health Care Workers (HCW) and 327 of visitors and parents. The nursing HH compliance was highest (49%) followed by medical compliance (24%, P < 0.001). HCW HH compliance was highest in intensive care units and the transplant unit (64-87%). The rate of appropriate HH for HCW was 22.6%. HCW most commonly used soap and water (76.1%). The HH procedure was more likely to be appropriate when soap and water were used as compared with alcohol based hand rub (64.6% and 47.5%, P = 0.006). A marginally significant association was identified between the HH compliance rate and the number of alcohol based hand rub dispensers per room (P = 0.057). In visitors and parents, the HH compliance was found to be 19%, whereas the rate of appropriate HH was 8.9%., Conclusions: Low levels of HH were observed.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib-based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL-pPCL and 17 with secondary PCL-sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR-group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow-up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow-up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: Hepatitis B is a vaccine preventable disease with intermediate endemicity in Greece. Patients with juvenile idiopathic arthritis (JIA) on immunomodulating therapy are prone to infection or reactivation of hepatitis B virus (HBV). The aim of this study is to define the immune status against HBV in children newly-diagnosed with JIA., Methods: Case-control prospective study including 89 JIA patients and 89 controls matched for age and gender. Eighty-nine JIA patients were included in the study (22 males), with a mean age of 6.8 years. Sera were tested for hepatitis B surface antigen, hepatitis B core antibody, and anti-HBs. Patients with anti-HBs titers ≥10 IU/L were considered immune. Data were analysed with SPSS 18.0 version., Results: In the JIA group 55% were HBV immune (anti-HBs level ≥10 IU/L) while in the control group 92% were immune against HBV (p<0.001). Antibody levels in the patient group were significantly lower compared to the control group. The mean concentration of anti-HBs levels in JIA patients was 18.3 IU/L versus 82.6 IU/L in the control group (p<0.001)., Conclusions: Antibody titers against HBV in fully vaccinated JIA patients due to start treatment are significantly lower compared to matched healthy children in this study. Diagnosis of JIA and older age were associated with the absence of protective antibodies. Although there is no evidence to support the introduction of a booster HBV dose in healthy children who mount low antibody response following immunisation, further studies are required to address this question in patients with JIA.

Setting: A hospital referral center for childhood tuberculosis (TB)., Objective: To evaluate the epidemiological and clinical features of childhood TB in the Greater Athens area in the last decade., Design: We retrospectively reviewed the medical records of patients aged <14 years treated for active TB between January 2000 and December 2009 at our pediatric TB clinic and compared the results with the patient turnover during the previous decade (1990-1999). Data concerning demographic and clinical characteristics were analyzed., Results: A total of 321 children (median age 5.57 years, 157 males) with active TB were identified. About one third originated from areas where TB was previously recognized to be highly endemic. Twenty-three children (7%) had extra-pulmonary TB, and 61% of them originated from TB-endemic areas. Bacteriological confirmation was obtained in 40% of patients from whom specimens were obtained: 1 of 26 (3.8%) strains was multidrug-resistant. Most cases with drug-resistant Mycobacterium tuberculosis were noted among immigrant children. The average annual TB incidence was estimated at 5.37 per 100 000 for children aged <14 years in the Greater Athens area. Time trend analysis for the 20-year period revealed a significant reduction in the total number of TB cases (P = 0.002) and in TB among children from low-incidence countries (P < 0.0001)., Conclusions: In our settings, active TB is decreasing among children of Greek origin; disease epidemiology and drug resistance is influenced by the increasing influx of immigrants from areas where the disease is highly prevalent.

Objectives: The WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) methodology is a standardized method of comparing antimicrobial use. The ATC/DDD is defined as the average maintenance daily dose of a drug used in a 70 kg adult, ignoring the considerable differences in body weight of neonates and children. The aim of this study was to develop a new standardized way of comparing rates of antimicrobial prescribing between European children's hospitals., Methods: This pilot study at four European children's hospitals (in the UK, Greece and Italy) collected data including demographics, antibiotic use, dosing and indication in children and neonates over a 14 day period., Results: A total of 1217 antibiotic prescriptions were issued with 47 different antibiotics used. Approximately half of all children and a third of all neonates received antibiotics, with wide variation between centres in the type and dose of antibiotic used. We propose a new pragmatic three-step algorithm. The first step includes a simple comparison of the proportion of hospitalized children on antibiotics by weight bands and the number of antimicrobials that account for 90% of total DDD drug usage (DU90%). The second step is a comparison of the dosing used (mg/kg/day). The third step is to compare overall drug exposure using DDD/100 bed days for standardized weight bands between centres., Conclusions: This novel method has the potential to be a useful tool to provide antibiotic use comparator data and requires validation in a large prospective point prevalence study.

Meningococcal disease remains a significant global cause of morbidity and mortality despite the availability of polysaccharide and conjugate vaccines. The implementation of monovalent meningococcal serogroup C vaccine in developed countries has significantly decreased the incidence of meningococcal disease, while the recent introduction of monovalent serogroup A conjugate vaccine in the African meningitis belt aims to reduce the incidence of high endemic disease in this area. Three quadrivalent meningococcal vaccines have already been licensed; a polysaccharide (MenACWY-PS) and two conjugated (MenACWY-DT and MenACWY-CRM) vaccines. An investigational MenACWY-TT vaccine is described in this article. Clinical trials in infants older than 9 months of age, toddlers, children, adolescents and adults have indicated that this vaccine is well tolerated and immunogenic. The inclusion of a spacer molecule coupled with the polysaccharide (for serogroups A and C) and tetanus toxoid as the carrier protein aims to elicit robust immune responses. The tolerability of this vaccine is comparable to that of polysaccharide quadrivalent vaccines and monovalent meningococcal serogroup C vaccines. More importantly, the immunogenicity, antibody persistence and induction of immune memory aim to provide protection to a wide range of susceptible subjects.

Objective: To evaluate the performance of the Gen-Probe Amplified MTD® Test (AMTD) for childhood tuberculosis (TB) diagnosis compared to conventional culture., Design: We retrospectively studied 121 childhood cases (73 males; median age 7 years, range 1-16). Pulmonary samples (104/152, 68%) included gastric aspirates (n = 53), induced sputum samples (n = 43), bronchial aspirates and bronchoalveolar lavage (n = 8). Extra-pulmonary samples (48/152, 32%) included lymph nodes (n = 34) and other sterile fluids (n = 14). Specimens were examined using acid-fast bacilli (AFB) microscopy, AMTD and bacterial culture using BACTEC™ MGIT™ 960 and Löwenstein-Jensen (LJ) media., Results: A clinical diagnosis of TB was made in 50/121 (41%) children (43/50 pulmonary disease). AFB microscopy was positive in 6%; Mycobacterium tuberculosis was recovered by culture from 16/50 (32%) and AMTD was positive in 29/50 (58%). AMTD sensitivity, specificity, positive predictive value and negative predictive value compared to culture were respectively 100%, 85%, 50% and 100%. For pulmonary vs. extra-pulmonary disease, the performance of AMTD compared to culture was respectively 100%, 77%, 46% and 100% vs. 100%, 97.5%, 75% and 100%., Conclusions: Nucleic acid amplification tests are more sensitive and very specific methods for the rapid detection of M. tuberculosis. The AMTD technique increases TB detection in children compared to conventional culture.

Background: Upper respiratory tract infections (URTIs) are common in children. The cause of URTIs is usually viral, but parents' attitudes often contribute to inappropriate prescription of antibiotics, promoting antibiotic resistance. The objective of this study was to document and analyse parental beliefs on antibiotic use for children with URTIs in Greece, a country with high levels of antibiotic use and antibiotic resistance., Methods: A knowledge-attitude-practice questionnaire was developed and distributed to Greek parents caring for children who were 5-6 years old, between January and July of the same school year. The sample of the study contained parents from all geographic areas of Greece., Results: The majority of Greek parents (80%) believed that UTRIs are mostly self-limited, although 74% of them expected to receive antibiotics when such a diagnosis was given. Earache was the most common reason for which parents expected antibiotics (45%). Greek parents rarely gave antibiotics to their children without medical advice (10%) and most (88%) believed that unnecessary antibiotic use drives antibiotic resistance and they were happy to receive symptomatic therapy if instructed by their physician. Almost 70% of parents confused antibiotics with other medicines used for symptomatic therapy for a child with URTI., Conclusion: Greek parents have a trusted relationship with their paediatrician and rarely give antibiotics without medical advice, indicating that parents contribute less than expected to antibiotic misuse. Parents also appreciate the benign course of most URTIs and the fact that unnecessary antibiotic use is harmful. More time needs to be invested in educating mostly physicians on the potential benefit from reducing antibiotic prescribing for children with URTI.

Objective: Antibiotics are the drugs most frequently prescribed for children, and most of them lack patent protection. The aim of this study was to evaluate off-label antibiotic use in three European countries., Methods: Data relating to all patients admitted to the neonatal intensive care units (NICUs) and paediatric wards of the participating centres were collected by the same investigator over a 2-week survey period between February and May 2009. The data included age, date of birth, weight, relevant medical history and diagnosis, together with details of all of the antibiotics prescribed (compound, route of administration, dose, and indication for use)., Results: The study involved 616 children (110 admitted to NICUs: 62 in the UK, 38 in Italy and 10 in Greece; 506 admitted to general paediatric wards: 265 in the UK, 94 in Italy and 147 in Greece). A total of 1,244 antibiotic prescriptions were issued (290 in NICUs and 954 in paediatric wards). The results showed that off-label antibiotic use is very common among European paediatric patients, with generally only slight, but sometimes significant differences between countries. However, this use relates almost exclusively to doses and indications, and rarely to age. The only antibiotics found to be used off-label in an age-related manner in paediatric clinical practice are meropenem for neonates and quinolones or linezolid for older children, which represent priorities for future studies., Conclusion: European-wide educational programmes are urgently needed to meet the objectives of improving paediatricians' working knowledge of the recommendations surrounding licensed antibiotics-use in children, and of reducing uncontrolled patterns of prescribing.

During 1997-2006, general practitioner consultations for skin conditions for children <18 years of age in England increased 19%, from 128.5 to 152.9/1,000 child-years, and antistaphylococcal drug prescription rates increased 64%, from 17.8 to 29.1/1,000 child-years. During the same time period, hospital admissions for Staphylococcus aureus infections rose 49% from 53.4 to 79.3/100,000 child-years.

Objective: To analyse changes in clinical indications for community antibiotic prescribing for children in the UK between 1996 and 2006 and relate these findings to the new NICE guidelines for the treatment of upper respiratory tract infections in children., Study Design: Retrospective cohort study., Method: The IMS Health Mediplus database was used to obtain annual antibiotic prescribing rates and associated clinical indications in 0-18-year-old patients between 1 January 1996 and 31 December 2006 in the UK., Results: Antibiotic prescribing declined by 24% between 1996 and 2000 but increased again by 10% during 2003-2006. Respiratory tract infection was the most common indication for which an antibiotic was prescribed, followed by "abnormal signs and symptoms", ear and skin infections. Antibiotic prescriptions for respiratory tract infections have decreased by 31% (p<0.01) mainly because of reduced prescribing for lower respiratory tract infections (56% decline, p<0.001) and specific upper respiratory tract infections including tonsillitis/pharyngitis (48% decline, p<0.001) and otitis (46% decline, p<0.001). Prescribing for non-specific upper respiratory tract infection increased fourfold (p<0.001). Prescribing for "abnormal signs and symptoms" increased significantly since 2001 (40% increase, p<0.001)., Conclusion: There has been a marked decrease in community antibiotic prescribing linked to lower respiratory tract infection, tonsillitis, pharyngitis and otitis. Overall prescribing is now increasing again but is associated with non-specific upper respiratory tract infection diagnoses. General practitioners may be avoiding using diagnoses where formal guidance suggests antibiotic prescribing is not indicated. The new NICE guidance on upper respiratory tract infections is at risk of being ignored.