Publications by authors named "Havatzelet Yarden-Bilavsky"

34 Publications

Transient Cardiac Injury in Adolescents Receiving the BNT162b2 mRNA COVID-19 Vaccine.

Pediatr Infect Dis J 2021 Jun 2. Epub 2021 Jun 2.

From the Department of Pediatrics C Department of Pediatrics B Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Cardiology Department, Schneider Children's Medical Center of Israel, Petah Tikva, Israel Pediatric Intensive Care Unit, Dana-Dwek Children's Hospital, Tel-Aviv Medical Center, Tel-Aviv, Israel Pediatric Intensive Care Unit, Meir Medical Center, Kfar Saba, Israel Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Vaccines are paramount in the effort to end the coronavirus disease 2019 global epidemic. BNT162b2 is approved for the vaccination of adolescents over 16 years of age. Systemic adverse events were scarce though the pretested cohort of this age group was relatively small. The aim of the current study is to raise awareness for potential adverse reactions.

Methods: This is a case series of patients diagnosed with perimyocarditis following vaccination. Patients were compiled from 3 pediatric medical centers in Israel through a network of pediatricians and data regarding those cases was collected. In addition, incidence of perimyocarditis during the vaccination period was compared with previous years.

Results: All patients were males 16-18 years old, of Jewish descent, who presented with chest pain that began 1-3 days following vaccination (mean, 2.1 days). In 6 of the 7 patients, symptoms began following the 2nd dose and in 1 patient following the 1st dose. All cases were mild and none required cardiovascular or respiratory support. The incidence of perimyocarditis during the vaccination period was elevated in comparison to previous years.

Conclusions: This case series describes a time association between coronavirus disease 2019 vaccine and perimyocarditis in adolescents. All cases were mild, although only long-term follow-up can reveal the true impact of this cardiac injury. While it seems that the incidence of perimyocarditis during the vaccination campaign period is increased, a more comprehensive data collection on a wider scale should be done. We hope this report will serve as a reminder to report events and allow for analysis of potential adverse reactions.
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http://dx.doi.org/10.1097/INF.0000000000003235DOI Listing
June 2021

Clinical Features and Comparison of Kingella and Non-Kingella Endocarditis in Children, Israel.

Emerg Infect Dis 2021 Mar;27(3):703-709

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.
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http://dx.doi.org/10.3201/eid2703.203022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920667PMC
March 2021

Factors predicting efficacy of ethanol lock therapy as catheter salvage strategy for pediatric catheter-related infections.

Pediatr Blood Cancer 2021 May 22;68(5):e28856. Epub 2020 Dec 22.

Pediatric Infectious Diseases Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: Catheter-related infections are difficult to cure, and failure rates are high. We aimed to evaluate the efficacy and safety of ethanol lock therapy (ELT) as catheter salvage strategy in children with central-line-associated bloodstream infection (CLABSI), and to identify factors associated with treatment failure.

Methods: Data were collected of all the children who received ELT for treatment of CLABSI during 2013-2018 due to failure of standard therapy or multiple catheter-related infections. Univariate and multivariate analyses of risk-factors for ELT failure were performed. Catheter salvage rates were compared to those achieved using systemic antimicrobials alone in an historical control group.

Results: A total of 123 ELT episodes among 95 patients were analyzed. The majority of patients had underlying hemato-oncological disorders. Approximately half the episodes occurred in patients with implantable ports. Early and late treatment failure rates of ELT were 16% (20/123) and 7% (9/123), respectively. Overall, successful catheter salvage was achieved in 78% (96/123) of episodes, compared to 54% using systemic antimicrobials alone (P < .001), including mycobacterium, candida, and most staphylococcus aureus infections. Adverse events were reported in 9% (11/123) of episodes and were mostly mechanical. Multivariate analysis identified four risk factors for ELT failure: Gram-positive bacteria, elevated C-reactive protein, signs of tunnel infection, and low absolute neutrophil counts.

Conclusions: Our findings support the use of ELT for catheter salvage in children with CLABSI who failed standard therapy or had multiple catheter-related infections. The identified variables associated with ELT failure may help identify patients who can most benefit from ELT.
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http://dx.doi.org/10.1002/pbc.28856DOI Listing
May 2021

Efficacy and Safety of a Weight-based Dosing Regimen of Valganciclovir for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients.

Transplantation 2019 08;103(8):1730-1735

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Valganciclovir has been widely used for cytomegalovirus (CMV) prophylaxis in solid-organ transplant recipients. However, the optimal dosing protocol and target exposure in children are still unclear. Specific data as to the efficacy and safety of low-dose/low-exposure regimens are lacking and urgently needed.

Methods: During 2010 to 2015, the clinical efficacy and safety of a weight-based regimen of valganciclovir of 17 mg/kg/day, with a stratified dose reduction for impaired creatinine clearance, given as a CMV prophylaxis for 3 to 6 months, was retrospectively evaluated among pediatric kidney and liver transplant recipients, 12 months posttransplantation. Incidence of CMV infection was assessed by periodic measurements of viral load; adverse events were evaluated.

Results: Eighty-three children who had undergone 86 transplantations and were treated with 17 mg/kg of valganciclovir were included. Median age was 9.77 years (range, 0.6 to 18.9). Twelve (14%) developed CMV infection: 1 during prophylaxis and 11 during follow-up. These events comprised 6 cases of asymptomatic viremia and 6 cases of a clinically significant disease without occurrences of tissue-invasive disease. Treatment-related adverse effects occurred in 7 patients (8%), mostly hematological, resulting in premature drug cessation.

Conclusions: Our results support the use of 17 mg/kg of valganciclovir for CMV prophylaxis in liver and kidney transplanted children as it showed satisfactory long-term efficacy and a good safety profile.
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http://dx.doi.org/10.1097/TP.0000000000002632DOI Listing
August 2019

High tacrolimus trough level variability is associated with rejections after heart transplant.

Am J Transplant 2018 10 13;18(10):2571-2578. Epub 2018 Aug 13.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post-HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post-HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P = .930). Patients in the high variability group exhibited higher long-term rejection rate (median total rejection score: 0.33 vs 0, P = .04) with no difference in rejection scores within the first year post-HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8-fold increased risk for any rejection beyond the first year post-HTx (P = .011). Mortality was associated only with cardiovascular complications (P = .018), with no effect of tacrolimus through level variability.
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http://dx.doi.org/10.1111/ajt.15016DOI Listing
October 2018

Hematologic Adverse Events Associated With Prolonged Valganciclovir Treatment in Congenital Cytomegalovirus Infection.

Pediatr Infect Dis J 2019 02;38(2):127-130

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d.

Methods: A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected.

Results: One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded.

Conclusions: Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.
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http://dx.doi.org/10.1097/INF.0000000000002079DOI Listing
February 2019

Inhaled corticosteroids increase blood neutrophil count by decreasing the expression of neutrophil adhesion molecules Mac-1 and L-selectin.

Am J Emerg Med 2016 Oct 6;34(10):1977-1981. Epub 2016 Jul 6.

Department of Pediatrics A, Schneider Children Medical Center, Israel; Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.

Objective: The objective was to investigate the effect of commonly used inhaled corticosteroids on white blood cell count (WBC) and to examine the mechanisms involved.

Methods: This randomized comparative study comprised 60 healthy adults. We measured the effects of budesonide (by face mask inhalation or aerosol inhaler), fluticasone (by inhaler), and saline inhalation (control) on WBC and the differential leukocyte count, especially the absolute neutrophil count (ANC). To elucidate the mechanisms involved, we measured the expression of the adhesion neutrophil ligands Mac-1 (CD11b) and L-selectin (CD62L), and granulocyte colony-stimulating factor serum levels.

Results: Six hours after a single-dose inhalation of budesonide, mean increases of 23.4% in WBC (95% confidence interval [CI], 11.3-35.4) and 30.1% in ANC (95% CI, 7.2-53.0) were noted. The percentage of neutrophils increased from 54.6% to 58.1% (P< .001). Inhaled fluticasone increased WBC and ANC by 12.6% (95% CI, 1.5-23.7) and 22.7% (95% CI, 6.2-39.2), respectively (P< .01 for both). The absolute lymphocyte and eosinophil counts did not change significantly from baseline. The expression of Mac-1 and L-selectin decreased by 51.0% (P< .01) and 30.9% (P= .02), respectively, following face mask inhalation of budesonide and by 39.8% (P= .01) and 17.4% (P= .17), respectively, following inhalation of fluticasone. No significant changes in granulocyte colony-stimulating factor levels were noted.

Conclusions: Glucocorticoid inhalation increases WBC by increasing ANC. Reduced neutrophil adhesion to the endothelial surface, mediated by decreased adhesion molecule expression on neutrophils, is a plausible mechanism. Physicians should be aware of the effect of inhaled corticosteroids on WBC, as it may influence clinical decisions, especially in the emergency department.
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http://dx.doi.org/10.1016/j.ajem.2016.07.003DOI Listing
October 2016

Extremely elevated C-reactive protein levels are associated with unfavourable outcomes, including death, in paediatric patients.

Acta Paediatr 2016 Jan 23;105(1):e17-21. Epub 2015 Nov 23.

Department of Paediatrics A, Schneider Children's Medical Centre, Petach Tikva (affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv), Israel.

Aim: The aim of this study was to investigate the clinical significance of extremely elevated C-reactive protein (CRP) levels in hospitalised children.

Methods: We searched the electronic database of a tertiary paediatric medical centre for all patients admitted in 2010-2013 with a CRP of ≥ 30 mg/dL, and these comprised the study group. The controls were the other admissions. Data were collected on demographics, admission details, pre-existing conditions, discharge diagnosis, laboratory results and clinical outcomes.

Results: Our study group comprised 435 (0.72%) of the 59,997 patients hospitalised during the study period. The mortality rate and mean hospital stays were significantly higher in the study group, and infectious diseases were the most common diagnoses, affecting 389 patients (89.4%), particularly pneumonia (47.1%). Higher CRP was correlated with low albumin levels (p < 0.01). Bacteraemia was the most prevalent diagnosis (38%) in the 84 oncology patients, with a crude mortality rate of 17.6%.

Conclusion: Infectious diseases, mainly bacterial, were the most common diagnoses in previously healthy children with CRP ≥ 30 mg/dL. Extremely elevated CRP levels were associated with an unfavourable clinical outcome, including high mortality, particularly in oncology patients. Paediatricians should be aware of the significance of extremely elevated CRP levels.
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http://dx.doi.org/10.1111/apa.13226DOI Listing
January 2016

C-Reactive protein levels in children with primary herpetic gingivostomatitis.

Isr Med Assoc J 2014 Nov;16(11):700-2

Emergency Department, Schneider children's Medical Center, Petah Tikva, Israel.

Background: C-reactive protein (CRP) is often used to distinguish bacterial from viral infections. However, the CRP level does have implications, which depend on the clinical scenario and are still under research.

Objectives: To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis.

Methods: The electronic database of a tertiary pediatric medical center was searched for all inpatients with a diagnosis of primary herpetic gingivostomatitis without bacterial coinfection. Background and clinical information was collected and CRP levels were analyzed.

Results: The study group consisted of 66 patients aged 8 months to 7.1 years who met the study criteria. The average CRP was 7.4 mg/dl (normal 0.5 mg/dl). More than a third of the patients had a level higher than 7 mg/dl.

Conclusions: High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections.
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November 2014

Apnea induced by respiratory syncytial virus infection is not associated with viral invasion of the central nervous system.

Pediatr Infect Dis J 2014 Aug;33(8):880-1

From the *Departments of Pediatrics C; †Departments of Pediatrics A, Schneider Children's Medical Center, Petach Tikva; ‡Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; §Central Virology Laboratory, Public Health Services, Israel Ministry of Health, Tel Hashomer; ¶Laboratory of Infectious Diseases, Felsenstein Medical Research Center; and ‖Pediatric Intensive Care Unit, Schneider Children's Medical Center, Petach Tikva, Israel.

We aimed to study whether direct central nervous system invasion is responsible for the neurologic manifestations seen in hospitalized infants with respiratory syncytial virus (RSV) infection. Cerebrospinal fluid from infants with RSV infection was tested for the detection of the following respiratory RNA viruses: RSV, influenza A and B, pandemic influenza H1N1, Parainfluenza-3, human metapneumovirus, adenovirus, parechovirus and enterovirus. All children tested negative for the presence of viral material in the cerebrospinal fluid. Our results support the notion that the mechanism of RSV-induced neurologic manifestations, including apnea, is not direct central nervous system invasion.
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http://dx.doi.org/10.1097/INF.0000000000000311DOI Listing
August 2014

Hospitalization for respiratory syncytial virus bronchiolitis and disease severity in twins.

Isr Med Assoc J 2013 Nov;15(11):701-4

Department of Pediatrics 2C, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease and hospitalization in infants and young children. Infants of multiple births, who are often premature, might be more susceptible to developing a more severe RSV infection than singletons.

Objective: To assess the impact of multiple births on the severity of RSV infection and define risk factors for acquiring RSV infection in infants of multiple birth.

Methods: Clinical data on infants hospitalized with RSV infection between 2008 and 2010 were retrospectively collected.

Results: Twins comprised 7.6% (66/875) of hospitalized infants with RSV bronchiolitis during the study period. Infants in the twin group were younger (122.4 +/- 131.7 vs. 204.5 +/- 278.8 days, P = 0.014), had a lower mean gestational age (35.3 +/- 2.6 vs. 38.6 +/- 2.5 weeks, P < 0.001), and were more likely to have been born prematurely compared with singleton infants (65.6% vs. 13%, P < 0.001). On a multivariable logistic regression analysis, young age, early gestational age and male gender were the only variables identified as risk factors for pediatric intensive care unit admission (P < 0.001, P < 0.001 and P = 0.03, respectively). In contrast, the mere fact of a child being a twin was not found to be a significant risk factor for disease severity. In addition, if one twin is hospitalized due to RSV infection, the other has a 34% chance of also being hospitalized with bronchiolitis. Young age was a significant risk factor for hospitalization of the second twin (P < 0.001) CONCLUSIONS: Our findings suggest that twins hospitalized with RSV bronchiolitis do not have an increased risk for severe infection as compared to singletons. However, a twin of an infant hospitalized with RSV infection has a considerable risk of also being hospitalized with bronchiolitis, thus close monitoring is recommended.
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November 2013

Fever survey highlights significant variations in how infants aged ≤60 days are evaluated and underline the need for guidelines.

Acta Paediatr 2014 Apr;103(4):379-85

Department of Pediatrics A, Schneider Children's Medical Center, Petah Tiqva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Aim: To assess the common practices for evaluating and treating febrile infants aged ≤60 days in a nationwide survey.

Methods: Questionnaires were administrated to inpatient paediatric departments in all 25 hospitals in Israel.

Results: Of the 25 centres surveyed (100% response rate), only 36% had written protocols concerning the approach to young febrile infants. The existence of a written protocol was significantly associated with the level of medical centre (tertiary versus primary and secondary, p = 0.041) and with the number of local paediatric infectious disease specialists (p = 0.034). In 13 (52%) hospitals, a normal white blood cell count was defined as 5000-15 000 cells/mL and 20 (80%) centres use C-reactive protein. Hospitalisation was mandatory in most (96%) centres for all neonates aged ≤28 days. Low-risk infants aged 29-60 days were hospitalised in 68.4% of the primary and secondary hospitals, compared with 33.3% tertiary centres. Ampicillin and gentamicin was the routine empiric antibiotic treatment for febrile infant in 92% of centres.

Conclusion: Significant differences exist among centres in the evaluation of febrile infants aged ≤60 days exist. These differences reflect the lack of, and highlight the need for, national or international guidelines for the evaluation of fever in this age group.
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http://dx.doi.org/10.1111/apa.12560DOI Listing
April 2014

Severe infections in twins.

Pediatr Infect Dis J 2013 Jul;32(7):788-9

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

We describe 4 sets of twins 5 days to 10 weeks of age with a serious bacterial or viral infection. The issue of the occurrence of a simultaneous infection in twins and the clinical dilemma of the appropriate evaluation and treatment of an asymptomatic co-twin of infants with a serious infection is discussed.
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http://dx.doi.org/10.1097/INF.0b013e31828a3277DOI Listing
July 2013

Fusobacterium necrophorum mastoiditis in children - emerging pathogen in an old disease.

Int J Pediatr Otorhinolaryngol 2013 Jan 25;77(1):92-6. Epub 2012 Oct 25.

Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Anaerobic bacteria are uncommon etiologic agents of acute mastoiditis in children. However, recent studies suggest an increase in the incidence of Fusobacterium necrophorum mastoid infections in the last two decades.

Methods: A surveillance study performed over 3.5 years in a tertiary pediatric medical center identified 7 children with acute F. necrophorum mastoiditis. Clinical, laboratory, and treatment data were collected by file review.

Results: Five of the 7 children presented in the last year of the study. All 7 children were less than 26 months old on admission, and none had a history of otogenic infections. All cases were characterized by significantly elevated levels of inflammatory markers. All were diagnosed as complicated mastoiditis with abscess formation. Four children had an epidural abscess, three children had evidence of osteomyelitis beyond the mastoid bone, and four children had imaging evidence of sinus vein thrombosis. All seven children required cortical mastoidectomy with ventilatory tubes insertion and two children required more than one surgical intervention. During follow-up, two children had recurrent episodes of mastoiditis due to other pathogens.

Conclusion: Our data support the literature suggesting that the occurrence of F. necrophorum mastoiditis among children is rising. Acute coalescent mastoiditis due to F. necrophorum is associated with a complicated course and warrants particular attention by pediatricians, infectious disease experts, and ear, nose and throat specialists.
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http://dx.doi.org/10.1016/j.ijporl.2012.10.003DOI Listing
January 2013

Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A Reminder of the Phenomenon of Apparent Vaccine Failure.

Case Rep Infect Dis 2012 16;2012:950107. Epub 2012 Aug 16.

Department of Pediatrics C, Schneider Children's Medical Center, 14 Kaplan Street, 49202 Petach Tikva, Israel.

We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.
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http://dx.doi.org/10.1155/2012/950107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431063PMC
September 2012

Month-by-month age analysis of the risk for serious bacterial infections in febrile infants with bronchiolitis.

Clin Pediatr (Phila) 2011 Nov 17;50(11):1052-6. Epub 2011 Jun 17.

Schneider Children's Medical Center, Petah Tiqva, Israel.

Objective: This study's aim was to assess the risk of serious bacterial infections (SBI) in each of the first 3 months in hospitalizes febrile infants with bronchiolitis.

Patients And Methods: The risk of SBI was compared between hospitalized infant with or without bronchiolitis by age in months.

Results: A total of 1125 febrile infants aged ≤3 months were admitted during the study period, 948 without and 177 with bronchiolitis. The incidence of SBI was significantly lower among infants with bronchiolitis compared with those without (4% vs 12.2%, P < .001). However, within the subgroup of neonates with bronchiolitis aged ≤28 days, the incidence of SBI was 9.7% and was not significantly lower than in neonates without bronchiolitis.

Conclusion: The risk of SBI among febrile infants with bronchiolitis is significantly lower compared with febrile infants without bronchiolitis, but only after the neonatal period in which the risk for urinary tract infection was relatively high (9.7%).
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http://dx.doi.org/10.1177/0009922811412949DOI Listing
November 2011

Adrenal insufficiency during physiological stress in children after kidney or liver transplantation.

Pediatr Transplant 2011 May 28;15(3):314-20. Epub 2011 Mar 28.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

The aim of this study was to assess the prevalence and risk factors of AI in pediatric recipients of kidney or liver transplantation admitted because of a physiological stress episode and to identify patients that might be at risk of adrenal crises by clinical and laboratory parameters at admission. Adrenal function was prospectively evaluated by a standard (250 μg) adrenocorticotropin test in 48 recipients. Data on clinical and laboratory parameters were collected. AI was diagnosed in 11 patients: 10/32 (31.3%) children on long-term steroid treatment and 1/16 (6.25%) untreated. The only risk factor for AI was corticosteroids cumulative dose of >0.15 mg/kg/day during the last six months (p = 0.02, OR 6.67; 95% CI: 0.97-45.79). No correlation was found between clinical or laboratory signs of adrenal crisis on admission and the presence of AI. None of the patients with AI who did not receive stress dose (n = 8) developed adrenal crisis. AI is relatively common in children receiving prolonged corticosteroid treatment after kidney or liver transplantation. Clinical parameters on admission could not reliably identify patients with AI. Universal administration of a stress dose during physiological stress might not be required. However, at this point, the only method to identify patients that will benefit from a stress dose is through the ACTH test.
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http://dx.doi.org/10.1111/j.1399-3046.2010.01466.xDOI Listing
May 2011

A search for the 'Holy Grail' in the evaluation of febrile neonates aged 28 days or less: a prospective study.

Scand J Infect Dis 2011 Apr 20;43(4):264-8. Epub 2010 Dec 20.

Department of Pediatrics C, Schneider Children's Medical Center, Petah Tiqva, Israel.

Objective: To determine the reliability of low-risk criteria to exclude serious bacterial infection (SBI) in febrile neonates aged ≤28 days.

Methods: All febrile neonates who were hospitalized for fever evaluation were prospectively divided into 2 groups by risk status for SBI. The following criteria were used to define low risk: (1) unremarkable medical history; (2) well-appearing; (3) no focal signs of infection; (4) white blood cell count between 5000 and 15,000/mm(3); (5) normal urinalysis; (6) no mucoid or bloody diarrhoea.

Results: Of the 465 enrolled neonates, 177 (38.1%) were considered high risk for SBI and 288 (61.9%) low risk. SBIs were found in 55 (31.1%) neonates in the high-risk group compared to 10 (3.5%) in the low-risk group (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the criteria for all types of SBI were 84.6% (95% confidence interval (CI) 73.9-91.4%), 69.5% (95% CI 64.8-73.8%), 31% (95% CI 27.3-35.1%) and 96.5% (95% CI 94.3-98%), respectively.

Conclusions: The defined criteria are not sufficiently reliable to exclude an SBI or an invasive SBI. We therefore suggest that all febrile neonates in this age group should be hospitalized for complete evaluation and consideration of empirical intravenous antibiotic treatment.
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http://dx.doi.org/10.3109/00365548.2010.544670DOI Listing
April 2011

Serious bacterial infections in neonates with fever by history only versus documented fever.

Scand J Infect Dis 2010 Dec 4;42(11-12):812-6. Epub 2010 Jun 4.

Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

The objective of the study was to assess the risk of serious bacterial infection (SBI) in hospitalized neonates aged ≤ 28 days with fever by history only compared to neonates with documented fever. Data regarding the presence of fever at presentation and during hospitalization, laboratory results and the diagnosis of an SBI were collected prospectively. Of the 399 neonates who met the inclusion criteria, 143 (35.8%) had fever by history only and 256 (64.2%) had documented fever at presentation. SBI was detected in 12 neonates in the history-only group (8.4%; urinary tract infection (UTI) in all cases) compared with 46 neonates with documented fever (18%; UTI in 33, UTI with bacteraemia in 4, isolated bacteraemia in 5 and pneumonia in 4). This difference was statistically significant (p = 0.008). Documented fever on admission was associated with an adjusted odds ratio of 3.23 (95% confidence interval 1.50-6.93, p = 0.003) of having an SBI. In hospitalized neonates aged ≤ 28 days, fever by history only is associated with a significantly lower rate of SBI, and particularly less invasive infections, than in neonates with documented fever. Since the risk is significantly lower, a more conservative approach to neonates without documentation of fever may be appropriate.
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http://dx.doi.org/10.3109/00365548.2010.492783DOI Listing
December 2010

Respiratory syncytial virus-positive bronchiolitis in hospitalized infants is associated with thrombocytosis.

Isr Med Assoc J 2010 Jan;12(1):39-41

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Background: Secondary thrombocytosis is associated with a variety of clinical conditions, one of which is lower respiratory tract infection. However, reports on thrombocytosis induced by viral infections are scarce.

Objectives: To assess the rate of thrombocytosis (platelet count > 500 x 10(9)/L) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection.

Methods: Clinical data on 469 infants aged < or = 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between RSV-positive and RSV-negative infants.

Results: The rate of thrombocytosis was significantly higher in RSV-positive than RSV-negative infants (41.3% vs. 29.2%, P=0.031). The odds ratio of an infant with bronchiolitis and thrombocytosis to have a positive RSV infection compared to an infant with bronchiolitis and a normal platelet count was 1.7 (P= 0.023, 95% confidence interval 1.07-2.72). There was no significant difference in mean platelet count between the two groups.

Conclusions: RSV-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.
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January 2010

Should complete blood count be part of the evaluation of febrile infants aged ≤2 months?

Acta Paediatr 2010 Sep;99(9):1380-4

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

Objective: To determine the utility and importance of total white blood cell count (WBC) and absolute neutrophil count (ANC) as markers of serious bacterial infection (SBI) in hospitalized febrile infants aged ≤2 months.

Patients And Methods: Data on WBC and ANC were collected prospectively for all infants aged ≤2 months who were hospitalized for fever at our centre. The patients were divided into two groups by the presence or absence of SBI.

Results: A total of 1257 infants met the inclusion criteria, of whom 134 (10.7%) had a SBI. The area under the ROC curve was 0.73 (95% CI: 0.67-0.78) for ANC, 0.70 (95% CI: 0.65-0.76) for %ANC and 0.69 (95% CI: 0.61-0.73) for WBC. The independent contribution of these three tests in reducing the number of missed cases of SBI was significant.

Conclusion: Complete blood cell count should remain as part of the routine laboratory assessment in this age group as it is reducing the number of missing infants with SBI. Of the three parameters, ANC and %ANC serve as better diagnostic markers of SBI than total WBC. However, more accurate tests such as C-reactive protein and procalcitonin should also be part of the evaluation of febrile infants in these age group as they perform better than WBC or ANC for predicting SBI.
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http://dx.doi.org/10.1111/j.1651-2227.2010.01810.xDOI Listing
September 2010

[Ill-appearing febrile 5-week-old infant: the rule of empiric treatment].

Harefuah 2009 Nov;148(11):759-60, 794

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

This is a case study of a 5-week-old child, after prolonged hospitalization in the Neonatal Intensive Care Unit, with fever and urinary tract infection caused by extended-spectrum beta-lactamase (ESBL)-producing, gentamicin-resistant, Escherichia coli. This case highlights the importance of taking risk factors for resistant bacterial infection into account in young, ill-appearing infants, and suggests that in some cases empirical antibiotic treatment should be even broader than recommended by current guidelines.
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November 2009

[The relationship between fever magnitude and serious bacterial infections in febrile infants less than two-months-old--a prospective study].

Harefuah 2009 Nov;148(11):752-5, 794

Department of Pediatrics A, Schneider Children's Medical Center, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: The evaluation and treatment of febrile infants below 2 months of age is inconsistent in hospitals in Israel. In some centers fever magnitude is considered to be one of the parameters that influence decision making as well as management.

Objective: To assess the correlation between fever magnitude and the risk of serious bacterial infections (SBI) in hospitalized infants under the age of 2 months.

Patients And Methods: The study group consisted of all infants < or = 2 months hospitalized at the Schneider Children's Medical Center for evaluation of fever from September 2006 to December 2008. Data were collected prospectively regarding the magnitude of fever on admission, during hospitalization, and diagnosis of SBI.

Results: SBI was detected in 90 (10.8%) of the 833 infants that met the inclusion criteria (UTI in 68, bacteremia in 11, pneumonia in 10 and enteritis in one). The mean fever at presentation was 38.4 degrees in the group of infants with SBI compared to 38.3 degrees in the infants without SBI (p=NS). Mean maximal fever during hospitalization was 38.6 degrees in the two groups. No correlation was found between the degree of fever and the type of SBI.

Conclusion: There is no correlation between fever magnitude and the risk of SBI in hospitalized infants aged < or = 2 months. Therefore, we suggest that fever magnitude should not be a factor in the decision of evaluating febrile infants in this age group.
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November 2009

C-reactive protein as a marker of serious bacterial infections in hospitalized febrile infants.

Acta Paediatr 2009 Nov 6;98(11):1776-80. Epub 2009 Aug 6.

Department of Paediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

Objective: To determine the potential predictive power of C-reactive protein (CRP) as a marker of serious bacterial infection (SBI) in hospitalized febrile infants aged < or =3 months.

Patients And Methods: Data on blood CRP levels were collected prospectively on admission for all infants aged < or =3 months who were hospitalized for fever from 2005 to 2008. The patients were divided into two groups by the presence or absence of findings of SBI.

Results: A total of 892 infants met the inclusion criteria, of whom 102 had a SBI. Mean CRP level was significantly higher in the infants who had a bacterial infection than in those who did not (5.3 +/- 6.3 mg/dL vs. 1.3 +/- 2.2 mg/dL, p < 0.001). The area under the ROC curve (AUC) was 0.74 (95% CI: 0.67-0.80) for CRP compared to 0.70 (95% CI: 0.64-0.76) for white blood cell (WBC) count. When analyses were limited to predicting bacteremia or meningitis only, the AUCs for CRP and WBC were 0.81 (95% CI: 0.66-0.96) and 0.63 (95% CI: 0.42-0.83), respectively.

Conclusion: C-reactive protein is a valuable laboratory test in the assessment of febrile infants aged < or =3 months old and may serve as a better diagnostic marker of SBI than total WBC count.
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http://dx.doi.org/10.1111/j.1651-2227.2009.01469.xDOI Listing
November 2009

Clinical, laboratory, and microbiological differences between children with simple or complicated mastoiditis.

Int J Pediatr Otorhinolaryngol 2009 Sep 17;73(9):1270-3. Epub 2009 Jun 17.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: To assess clinical, laboratory, and microbiological differences between children with simple and complicated mastoiditis.

Patients And Methods: Data on all children who were hospitalized at a tertiary center for acute mastoiditis over a 5-year period were collected from the computerized files. Findings were compared between those with simple mastoiditis vs. cases with intra- or extra-cranial complications.

Results: Of the 308 children with acute mastoiditis, 55 (17.9%) had complicated disease. This group was characterized by a significantly higher maximal fever at presentation and higher absolute neutrophil count and C-reactive protein level than the children with simple disease. There was no statistically significant between-group difference in age, history of otitis media, prior antibiotic treatment, days of illness before presentation, absolute leukocyte count, and platelet count. No difference was detected between the groups in the penicillin and ceftriaxone susceptibility of the Streptococcus pneumoniae isolates.

Conclusion: High-grade fever, high absolute neutrophil count, and high C-reactive protein level may serve as clinical and laboratory markers of complicated mastoiditis. Children with these findings warrant close follow-up and perhaps, earlier surgical intervention.
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http://dx.doi.org/10.1016/j.ijporl.2009.05.019DOI Listing
September 2009

Bilateral primary spontaneous pneumothorax: buffalo chest.

Pediatr Emerg Care 2009 Jan;25(1):33-4

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

A case of bilateral primary spontaneous pneumothorax ("buffalo chest") in a previously healthy man is described. The clinical presentation and treatment options are discussed.
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http://dx.doi.org/10.1097/PEC.0b013e318191db2bDOI Listing
January 2009

Are grunting respirations a sign of serious bacterial infection in children?

Acta Paediatr 2008 Aug 6;97(8):1086-9. Epub 2008 May 6.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

Aim: To assess the significance of grunting respirations in children and their potential association with serious bacterial infections, and to identify characteristics unique to this patient group.

Patients And Methods: A prospective case-control design was used. Data were collected on all children who were hospitalized with grunting respirations in our department of paediatrics over a 13-month period. The enrolled patients were divided into three groups: previously healthy children aged 3 months or less, previously healthy children aged more than 3 months and children with chronic illness at any age. The findings were compared to matched controls hospitalized for similar symptoms but without grunting respirations.

Results: Grunting respirations were documented in 149 of the 3334 admissions (4.5%) during the period of study. The incidence was higher in children aged 3 months or less (7.5%) and lower in children older than 3 months (3.9%). Fever and respiratory symptoms were common (83.9% and 65.1%, respectively). Heart rate was the only vital sign that was significantly different between the study and control groups. Serious bacterial infection occurred more frequently in the study group (31.5% vs. 14.8%, p < 0.001, OR 2.14, 95% CI 1.36-3.36). Comparisons between the groups showed that grunting respirations were a sign of serious bacterial infection in previously healthy children older than 3 months (p = 0.007, OR 1.95, 95% CI 1.21-3.13) and in children with a chronic disease of any age (p = 0.033, OR 7.0, 95% CI 1.0-49.7 respectively), but not in previously healthy children younger than 3 months (p = 1).

Conclusion: The incidence and importance of grunting respirations in hospitalized children depend on patient's age and previous medical status. A finding of grunting respirations in a previously healthy child aged over 3 months or in a chronically ill child should alert the physician to seek further evidence of bacterial infection, especially pneumonia.
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http://dx.doi.org/10.1111/j.1651-2227.2008.00839.xDOI Listing
August 2008

Effect of benzathine penicillin treatment on antibiotic susceptibility of viridans streptococci in oral flora of patients receiving secondary prophylaxis after rheumatic fever.

J Infect 2008 Apr 4;56(4):244-8. Epub 2008 Mar 4.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.

Objective: To assess the level of antibiotic resistance of viridans streptococci in the oral flora of children with a history of rheumatic fever, receiving long-term monthly intramuscular benzathine penicillin G prophylaxis.

Patients And Methods: Oral swabs from patients receiving monthly penicillin G prophylaxis for rheumatic fever were cultured and tested for viridans streptococci. The E-test was used to test susceptibility to penicillin G, clindamycin, clarithromycin and rifampin. Findings were compared with samples from healthy children who had not been exposed to antibiotic treatment for at least 2 months.

Results: Twenty-six patients and 20 control children were included in the study. Duration of intramuscular antibiotic treatment ranged from 5 months to 13.5 years. Sixty isolates of viridans streptococci species were obtained, with a similar distribution in the two groups. Intermediate resistance to penicillin (MIC 0.25-2 mg/L) was documented in 10 of the 32 isolates (31.2%) in the study group, and high resistance in none, compared to seven of 28 isolates (25%) with intermediate or high resistance in the control group (p=NS). All isolates in the study group and all but one in the control group were susceptible to clindamycin, and all isolates from both groups were susceptible to rifampin. One isolate (3.1%) in the study group and two (7.1%) in the control group were resistant to clarithromycin.

Conclusion: Monthly Intramuscular penicillin prophylaxis has no effect on the antibiotic susceptibility of viridans streptococci in oral flora in children with a history of rheumatic fever, receiving secondary prophylaxis after rheumatic fever, regardless of the duration of treatment.
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http://dx.doi.org/10.1016/j.jinf.2008.01.006DOI Listing
April 2008