Publications by authors named "Liat Ashkenazi-Hoffnung"

43 Publications

[THE ROLE OF BONE SCINTIGRAPHY IN THE DIAGNOSIS OF CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS IN CHILDREN].

Harefuah 2021 Jul;160(7):429-432

Day Care Department, Schneider Children's Medical Center, Tel Aviv University.

Introduction: This case report presents a teenage girl hospitalized due to fever, left wrist pain and elevated inflammatory markers. These clinical findings, as well as a lytic lesion seen on plain radiographs and MRI in the distal left radius, led to the working diagnosis of acute osteomyelitis. Following 4 weeks of antibiotic therapy, a bone scan was conducted due to inadequate clinical response. It showed additional skeletal lesions and led to the final diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Treatment was changed to anti-inflammatory medications with a good response. This article presents key features of CRMO and emphasizes the role of skeletal scintigraphy in establishing the diagnosis.
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July 2021

Peripheral Venous Catheter-related Bloodstream Infections in Hospitalized Children: The Role of Gram-negative Bacteria.

Pediatr Infect Dis J 2021 Jul 6. Epub 2021 Jul 6.

From the Department of Pediatrics A, Schneider Children's Medical Center, Petah Tikva, Israel Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Infectious Diseases Unit Department of Pediatrics B Department of Pediatrics C Pediatric Heart Institute, Schneider Children's Medical Center, Petah Tikva, Israel Microbiology Laboratory, Rabin Medical Center, Petah Tikva, Israel.

Background: Peripheral venous catheter (PVC) is the most used vascular access device in medicine, allowing administration of intravenous fluids and medications. Known complications associated with PVC include extravasation, phlebitis and rarely bloodstream infection (BSI). Data regarding PVC-related BSI in children are lacking. Our aim was to evaluate the epidemiology, clinical and microbiologic characteristics of pediatric inpatients with PVC-related BSI.

Methods: A retrospective study was conducted in a pediatric tertiary care center. Children with BSI, admitted to general pediatric departments during 2010-2019, were identified and their medical records examined. Patients with BSI and phlebitis were further characterized and included in the analysis. We excluded patients with central venous catheters, other identified source of infection and with BSI upon admission. Data collected included patients' demographics and clinical and microbiologic characteristics.

Results: Twenty-seven children with PVC-related BSI were identified and included in the study, consisting of 0.2% of the total BSI cases. Patient's median age was 24 (range, 1.5-213) months, 14/27 (52%) were female and 6 (22%) were previously healthy while 21 (78%) had prior medical conditions. Sixteen (59.3%) patients had Gram-negative BSI and 6 (22.2%) Gram-positive bacteria. Polymicrobial infection occurred in 4 (14.8%) patients and Candida albicans in 1 (3.7%) patient. The most common isolated bacteria were Klebsiella spp and Staphylococcus aureus. Longer dwell-time was a predictor of Gram-negative bacteria.

Conclusions: PVC-related BSI due to Gram-negative bacteria was more common than to Gram-positive bacteria. Clinicians should consider an initial broad-spectrum antibiotic coverage for PVC-related BSI in hospitalized pediatric patients.
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http://dx.doi.org/10.1097/INF.0000000000003255DOI Listing
July 2021

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

Emerg Infect Dis 2021 03;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

Isavuconazole As Successful Salvage Therapy for Mucormycosis in Pediatric Patients.

Pediatr Infect Dis J 2020 08;39(8):718-724

From the Day Hospitalization Department, Infectious Diseases Unit, Hemato-Oncology Department, Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva.

Background: Mucormycosis is a rare but emerging life-threatening fungal disease with limited treatment options. Isavuconazole is a new triazole that has shown efficacy in adults for primary and salvage treatment of mucormycosis. However, data in children are scarce.

Methods: The demographic and clinical data of pediatric patients with proven mucormycosis who were treated with isavuconazole in 2015 to 2019 at 2 centers were collected.

Results: Four children of median age 10.5 years (range 7-14) met the study criteria. Three had underlying hematologic malignancies, and 1 had sustained major trauma. Isavuconazole was used as salvage therapy in all: in 3 patients for refractory disease, and in 1 after intolerance to another antifungal drug. Isavuconazole was administered alone or combined with other antifungal agents. Following treatment and surgical intervention, complete clinical, radiologic and mycologic responses were documented in all patients. A literature review identified 8 children with mucormycosis who were successfully treated with isavuconazole, as salvage therapy in the majority.

Conclusion: Our limited experience supports the use of isavuconazole as salvage therapy in pediatric mucormycosis.
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http://dx.doi.org/10.1097/INF.0000000000002671DOI Listing
August 2020

Understanding Newborn Hepatitis B Immunization Refusal: One Size Does Not Fit All.

Isr Med Assoc J 2020 Mar;22(3):191-192

Pediatric Infectious Diseases Unit and the Center for Microbiome Research, Shamir Medical Center (Assaf Harofeh), Zerifin, Israel.

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March 2020

Infections in Children With Nephrotic Syndrome: Twenty Years of Experience.

Clin Pediatr (Phila) 2020 06 1;59(7):692-698. Epub 2020 Mar 1.

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

Infections is a common complication of nephrotic syndrome (NS). Our objective was to evaluate the frequency and risk factors for serious bacterial infections (SBI) in febrile children with NS. We reviewed 239 admissions of 107 children with NS who were admitted with fever to a tertiary hospital in Israel, during 1995 to 2016. SBI was diagnosed in 35 admissions (14.6%), most commonly with pneumonia (n = 12), bacteremia/sepsis (n = 8), and urinary tract infection (n = 6). Patients with SBI were more likely to be female (60.0% vs 36.3%, = .008) and have nephrotic-range proteinuria (71.4% vs 43.6%, = .010) and edema (62.9% vs 27.0%, < .001) on admission. No differences were found between the SBI and non-SBI groups in the clinical and histopathological type of NS, immunosuppressive treatment, rate of pneumococcal vaccination, and prophylactic antibiotics. In summary, 1 of 7 children had SBI, most commonly pneumonia, bacteremia/sepsis, and urinary tract infection. Active nephrosis was associated with an increased risk for SBI.
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http://dx.doi.org/10.1177/0009922820908583DOI Listing
June 2020

Q Fever and Kingella kingae Endocarditis in a Toddler: A Rare Coinfection Case.

Pediatr Infect Dis J 2019 12;38(12):e336-e337

From the Department of Pediatrics B.

A toddler after tetralogy of Fallot graft repair in infancy was diagnosed with endocarditis. Blood cultures were positive for Kingella kingae and serology was positive Coxiella burnetii. He was treated medically and surgically. A postoperative specimen polymerase chain reaction confirmed a coinfection. A comprehensive patient history was imperative for identification of an unlikely infection at this age.
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http://dx.doi.org/10.1097/INF.0000000000002469DOI Listing
December 2019

Flavobacteriaceae Bacteremia in Children: A Multicenter Study.

Pediatr Infect Dis J 2019 11;38(11):1096-1099

From the Department of Pediatrics B, Schneider Children's Medical Center, Petach Tikva, Israel.

Background: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections.

Methods: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018.

Results: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin.

Conclusions: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.
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http://dx.doi.org/10.1097/INF.0000000000002449DOI Listing
November 2019

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

Atypical presentation of human ehrlichiosis and anaplasmosis in children in Israel.

Acta Paediatr 2019 09 17;108(9):1727-1728. Epub 2019 Jun 17.

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

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http://dx.doi.org/10.1111/apa.14882DOI Listing
September 2019

Pediatric Infectious Sacroiliitis: Characterization and Differentiation from Noninfectious Etiologies.

Pediatr Infect Dis J 2019 07;38(7):e134-e137

From the Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva.

Background: Pediatric sacroiliitis (SI) is an uncommon entity of infectious or inflammatory etiology. Recent data regarding pediatric SI are scarce. The study objective was to describe and compare the clinical features of pediatric infectious and noninfectious SI.

Methods: We reviewed files of children ≤18 years of age, admitted with SI in 2004-2017. Patients were grouped by etiology, infectious versus noninfectious. Clinical and laboratory indices, imaging, treatment protocols and outcome were compared.

Results: Study population included 40 patients with infectious SI (range: 3-192 months, median age: 15 months, 45% female) and 13 patients with noninfectious SI (range: 30-216 months, median age: 168 months, 62% females). Duration of symptoms before admission averaged 5.9 ± 7.5 days in the infectious group and 54.2 ± 96 days in the noninfectious group (P = 0.003). Symptoms observed solely in the infectious group included refusal to stand (n = 27, 77%); walk or crawl (n = 24, 65%); irritability (n = 20, 50%) and recent constipation event (n = 8, 20%). No significant differences in laboratory results were found. Infectious SI patients had uneventful medical history, rapid response to antibiotics and a higher rate of complete resolution of symptoms without recurrences.

Conclusions: An acute unilateral presentation in young patients ≤2 years of age, without chronic medical conditions, suggests an infectious etiology of SI anticipated to completely resolve with antibiotic treatment, not necessitating further workup for noninfectious etiologies.
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http://dx.doi.org/10.1097/INF.0000000000002340DOI Listing
July 2019

Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases.

J Clin Epidemiol 2019 08 28;112:20-27. Epub 2019 Mar 28.

Department of Pediatric Respiratory Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Objective: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases.

Study Design And Setting: Pediatricians from six countries adjudicated a diagnosis (i.e., bacterial infection, viral infection, or indeterminate) for febrile children. Diagnosis was reached when the majority of panel members came to the same diagnosis, leaving others inconclusive. We evaluated intraobserver and intrapanel agreement with 6 weeks and 3 years' time intervals. We calculated the proportion of inconclusive diagnosis for a three-, five-, and seven-expert panel.

Results: For both time intervals (i.e., 6 weeks and 3 years), intrapanel agreement was higher (kappa 0.88, 95%CI: 0.81-0.94 and 0.80, 95%CI: NA) compared to intraobserver agreement (kappa 0.77, 95%CI: 0.71-0.83 and 0.65, 95%CI: 0.52-0.78). After expanding the three-expert panel to five or seven experts, the proportion of inconclusive diagnoses (11%) remained the same.

Conclusion: A panel consisting of three experts provides more reproducible diagnoses than an individual expert in children with lower respiratory tract infection or fever without source. Increasing the size of a panel beyond three experts has no major advantage for diagnosis reproducibility.
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http://dx.doi.org/10.1016/j.jclinepi.2019.03.010DOI Listing
August 2019

Systemic corticosteroids may be beneficial for managing severe or refractory orbital cellulitis in children.

Acta Paediatr 2018 11 10;107(11):2028-2029. Epub 2018 Jul 10.

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

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http://dx.doi.org/10.1111/apa.14467DOI Listing
November 2018

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Eur J Clin Microbiol Infect Dis 2018 Jul 26;37(7):1361-1371. Epub 2018 Apr 26.

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

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.
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http://dx.doi.org/10.1007/s10096-018-3261-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015097PMC
July 2018

Risk factors for early invasive fungal infections in paediatric liver transplant recipients.

Mycoses 2018 Sep 20;61(9):639-645. Epub 2018 Jun 20.

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

Invasive fungal infections (IFIs) postliver transplantation are a frequent cause of morbidity and mortality; however, studies reporting on these infections in the paediatric population are scarce. To investigate the incidence and risk factors of IFIs in paediatric liver transplant recipients during the early posttransplantation period (≤3 months). Data were collected for all paediatric liver transplant recipients registered in a national transplantation center from 2004 to 2014. Using a stepwise logistic regression to identify independent risk factors for IFIs, a predictive model was formulated. Ten IFIs were identified in 81 liver transplant recipients (12.3%) all occurring during the first month posttransplantation. Candida species were responsible for nine cases (90%), of which four were non-albicans Candida (44%). Significant risk factors were identified; recipient of multiple blood product transfusions during transplantation, prolonged use of indwelling intravenous catheter, prolonged IV antibiotic treatment, surgical complications, pulse steroid treatment and living donor liver transplantation. The predictive model used two clinical parameters to define high-risk patients: a living donor transplantation and duration of IV antibiotic treatment (area under the ROC curve 0.918). IFIs are a significant complication occurring in the first month posttransplantation. Future studies are required to assess efficacy of targeted antifungal prophylaxis in high risk patients.
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http://dx.doi.org/10.1111/myc.12784DOI Listing
September 2018

Fusobacterium necrophorum as an Emerging Pathogen of Acute Mastoiditis.

Pediatr Infect Dis J 2019 01;38(1):12-15

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

Background: Recent reports have reported an increase in the incidence of acute mastoiditis because of Fusobacterium necrophorum. However, the crude incidence and the specific clinical and laboratory characteristics of F. necrophorum mastoiditis in children have not been described. Our aim was to describe these features to identify high-risk patients.

Methods: The electronic medical records of all children with acute mastoiditis at a tertiary medical center between July 2011 and December 2015 were analyzed. Using a stepwise logistic regression to identify independent risk factors for F. necrophorum, we formulated a predictive model.

Results: F. necrophorum was identified in 13% (19/149) of mastoiditis cases with an identifiable agent. Its incidence increased 7-fold from 2.8% in 2012 to 20.4% in 2015 (P = 0.02). F. necrophorum infection had unique clinical, laboratory and prognostic features. The vast majority had complications and underwent surgical intervention. The predictive model used 4 parameters to define high-risk patients for F. necrophorum infection at admission: females, winter/spring season, prior antibiotic treatment and a C-reactive protein value >20 mg/dL (area under receiver operating characteristic curve 0.929).

Conclusions: Clinicians should be aware of the increasing incidence of F. necrophorum mastoiditis and consider anaerobic cultures and specific anaerobic coverage in high-risk patients.
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http://dx.doi.org/10.1097/INF.0000000000002021DOI Listing
January 2019

Group A Streptococcal Brain Abscess in the Pediatric Population: Case Series and Review of the Literature.

Pediatr Infect Dis J 2018 10;37(10):967-970

Pediatric Infectious Disease Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Background: Group A Streptococcus (GAS) is a rare cause of central nervous system infections.

Methods: We describe 3 new cases of GAS brain abscess in previously healthy children treated by us between 2015 and 2016 and review the 5 cases reported in the literature since 1988.

Results: All 8 children received early empiric antibiotic therapy and surgical intervention, and 5 made a full recovery.

Conclusions: GAS brain abscess is a rare infection; however its incidence may be rising. We suggest that if patients show symptoms such as fever, vomiting and lethargy, with contiguous infection such as otitis media, mastoiditis, sinusitis or meningitis, GAS brain abscess should be suspected. Prognosis is expected to be good with early implementation of appropriate treatment.
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http://dx.doi.org/10.1097/INF.0000000000001947DOI Listing
October 2018

Fatal and Near-Fatal Non-allergic Reactions in Patients with Underlying Cardiac Disease Receiving Benzathine Penicillin G in Israel and Switzerland.

Front Pharmacol 2017 21;8:843. Epub 2017 Nov 21.

Pharmaceutical Division, Israeli Ministry of Health, Jerusalem, Israel.

Benzathine Penicillin G (BPG) is commonly used for treatment of penicillin-susceptible infections and secondary prevention of rheumatic fever. Death following administration of BPG is extremely rare-only a handful of cases have been described in the literature since the 1950's. In this case series from Israel and Switzerland, we describe nine cases of serious adverse reactions-six fatal reactions and three near-fatalities-occurring within minutes of receiving intramuscular BPG. Allergic reactions or faulty administration were not implicated in any of the cases; however, all patients had cardiac risk factors. This case series describes a relatively rare risk that should be borne in mind when prescribing BPG.
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http://dx.doi.org/10.3389/fphar.2017.00843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702457PMC
November 2017

Evaluation of two commercial real-time PCR assays for detection of carbapenemase genes in Enterobacteriaceae.

J Med Microbiol 2017 Nov 16;66(11):1612-1615. Epub 2017 Oct 16.

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

The implementation of PCR for the detection of carbapenemase genes enables rapid results with significant epidemiological implications. Two commercial real-time PCR assays, the Hylabs Hy-CRE and Sacace MDR MBL+KPC/OXA, were evaluated for the detection of the genes blaKPC, blaVIM, blaNDM, blaIMP and blaOXA-48-carbapenemasein a collection of 96 carbapenem-resistant Enterobacteriaceae strains with different resistant mechanisms. Both assays exhibited excellent diagnostic performance, with 100 % sensitivity and specificity.
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http://dx.doi.org/10.1099/jmm.0.000618DOI Listing
November 2017

Real-life comparison of three general paediatric wards showed similar outcomes for children with bronchiolitis despite different treatment regimens.

Acta Paediatr 2017 Sep 9;106(9):1507-1511. Epub 2017 Jun 9.

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

Aim: This study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary paediatric facility.

Methods: Patients with bronchiolitis who were younger than two years of age and were randomly allocated to three general wards at Schneider Children's Medical Center, Israel, after admission were included. Different treatment protocols in the wards were retrospectively compared.

Results: The study comprised 286 children. The clinical and laboratory parameters on admission were similar between the wards. In Ward C where nebulised hypertonic saline was infrequently administered (6.7%), the mean number of days with oxygen saturation under 92% and the meanlength of hospital stay (1.8 and 3.8 days) were significantly lower than Ward A (2.8 and 5.3 days) and Ward B, (2.9 and 4.7 days) where nebulised hypertonic saline was given more frequently (38.7%-74.7%). Multivariate analysis indicated that low saturation on admission, leukocytosis and use of nebulised hypertonic saline or adrenalin were independent predictors of a longer period of desaturation and hospital stay.

Conclusion: Different treatment protocols for bronchiolitis were used in three paediatric wards in this real-life study. No treatment regimen proved superior. Inhalations of hypertonic saline or adrenaline were associated with a longer hospital stay.
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http://dx.doi.org/10.1111/apa.13921DOI Listing
September 2017

Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel.

World J Pediatr 2017 Aug 29;13(4):341-345. Epub 2017 Apr 29.

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

Background: Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis of the small vessels occurring at a young age and considered as a benign self-limited disease. Due to its low prevalence, there are limited data on the presentation and complications of this disease.

Methods: All computerized files of children who were hospitalized at a tertiary pediatric center due to AHEI over a 10 year period were reviewed. Clinical, laboratory and histopathological data were collected.

Results: Twenty-six patients were included in our study, accounting for 0.7 cases per 1000 admissions of children aged 2 years or less. Mean age was 12.9 months. More than two thirds of the children had preceding symptoms compatible with a viral infection. Upon admission, all patients presented with typical findings of a rash and edema. Edema was most profound over the lower extremities (73%). Concomitant viral or bacterial infections were found in six children. Skin biopsy was performed in six patients revealing leukocytoclastic vasculitis. Thirteen children (50%) had systemic involvement including joint involvement (n=9), gastrointestinal hemorrhage (n=4), microscopic hematuria (n=1) and compartment syndrome of the limb (n=1). The latter was diagnosed in a patient with familial Mediterranean fever.

Conclusions: Our largest data series highlighted what is known regarding clinical and histological findings in children with AHEI. However, contrary to what was previously reported, we found a higher rate of systemic involvement. Although AHEI is a rare entity, pediatricians should be familiar with its presentation, management and our reported complications.
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http://dx.doi.org/10.1007/s12519-017-0032-7DOI Listing
August 2017

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients: A Prospective Pharmacokinetic Study.

Pediatr Infect Dis J 2017 08;36(8):745-750

From the *Department of Pharmacy, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zriffin, Israel; §Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ¶Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel; and ‖Biochemistry Laboratory, Assaf Harofeh Medical Center, Zriffin, Israel.

Background: Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens.

Methods: The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated.

Results: Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given.

Conclusions: The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.
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http://dx.doi.org/10.1097/INF.0000000000001595DOI Listing
August 2017

Children after renal transplantation hospitalized for fever: Is empirical antibiotic treatment always justified?

Pediatr Transplant 2017 Mar 2;21(2). Epub 2017 Jan 2.

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

Infections are a major cause of morbidity and mortality after renal transplantation. However, data focusing on children are scarce. The objective of this study was to investigate the frequency and predictors of bacterial infection in pediatric renal transplant recipients in a specific setting of hospitalization due to fever. Clinical and laboratory data were retrospectively collected for all pediatric renal transplant recipients hospitalized for fever in a national renal transplantation center from 2004 to 2012. One hundred and sixty-eight hospital admissions for fever of 52 children were analyzed. A bacterial etiology was diagnosed in 85 admissions (50.6%); 49 cases (57.6%) were documented microbiologically and 36 (42.4%) clinically. Risk factors and markers of bacterial infection included older age, presence of a central venous catheter, sonographic findings, and elevated inflammatory indices. C-reactive protein level was a more sensitive marker than white blood cell count and absolute neutrophil count. In patients without identified risk factors, no bacterial infections were diagnosed. Pediatric renal transplant recipients hospitalized for fever are at high risk of bacterial infections and usually require empirical antibiotic treatment at admission. However, there is a minority of low-risk patients in whom clinicians may consider withholding antibiotic treatment with close follow-up.
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http://dx.doi.org/10.1111/petr.12862DOI Listing
March 2017

Pseudomonas aeruginosa identified as a key pathogen in hospitalised children with aspiration pneumonia and a high aspiration risk.

Acta Paediatr 2016 Dec 12;105(12):e588-e592. Epub 2016 Aug 12.

Department of Pediarics B&C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: Data on the causative pathogens and optimal empirical therapy of aspiration pneumonia in children are limited. This study sought to describe the bacteriology of aspiration pneumonia in hospitalised children with a high aspiration risk.

Methods: Respiratory tract specimens were prospectively collected using the induced sputum technique from children with a high aspiration risk who were hospitalised for aspiration pneumonia in a tertiary paediatric medical centre from 2009 to 2014. Clinical, microbiological and treatment data were recorded and analysed for each admission.

Results: The cohort comprised 50 children with 235 hospital admissions. Of the 183 respiratory tract cultures performed, 110 were positive for bacteria, with 169 isolates, mostly Gram-negative. The most common Gram-negative pathogen was Pseudomonas aeruginosa. If patients had Pseudomonas aeruginosa isolation, the risk of them having the pathogen again was 81%. The multivariate analysis showed that the use of antibiotic prophylaxis and number of hospitalisations were significantly associated with Pseudomonas aeruginosa isolation.

Conclusion: Gram-negative bacilli, especially Pseudomonas aeruginosa, were the major causative agents of paediatric aspiration pneumonia in our study. Empiric antipseudomonas treatment should be considered, particularly in patients who are receiving antibiotic prophylaxis, have experienced recurrent hospitalisations or with previous respiratory cultures that showed Pseudomonas aeruginosa isolation.
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http://dx.doi.org/10.1111/apa.13523DOI Listing
December 2016

Using the Rochester criteria to evaluate infantile fever is more effective in males than females.

Acta Paediatr 2016 Aug 22;105(8):e356-9. Epub 2016 Jun 22.

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

Aim: The reliability of low-risk and high-risk criteria in evaluating febrile infants aged up to 60 days has been well documented. The aim of this study was to evaluate gender differences in the reliability of these criteria in order to exclude serious bacterial infection (SBI) in febrile infants.

Methods: This study used the Rochester risk criteria, the study group was divided into low- or high-risk status for SBI, and the data were stratified by gender. SBI was defined as a urinary tract infection, bacteraemia, meningitis or bacterial enteritis.

Results: We enrolled 1896 infants (58.3% males), and SBIs were found in 10.6% of the males and 8% of the females (p = 0.21). The sensitivity of the risk criteria was 91.5% for the males and 73.4% (p < 0.05) for the females, and the positive likelihood ratio was 2.64 in the males versus 2.14 in the females (p < 0.001). A multivariable analysis showed that high-risk male patients were more than two times more likely to develop a bacterial infection than high-risk females.

Conclusion: The Rochester risk criteria had a significantly higher sensitivity and positive likelihood ratio in males. Our findings suggest that clinicians should take gender into account when evaluating febrile infants.
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http://dx.doi.org/10.1111/apa.13471DOI Listing
August 2016

Secondary bacteremia following adenovirus infection.

Infect Dis (Lond) 2016 4;48(5):403-5. Epub 2015 Dec 4.

b Sackler Faculty of Medicine , Tel Aviv University , Tel Aviv ;

Adenovirus is a common pediatric pathogen responsible for a wide variety of infections. Despite this, secondary bacteremia following an adenovirus infection has not been previously systematically described. Herein, we describe seven cases of secondary bacteremia following an adenovirus infection in hospitalized children during an 8-year period. Pediatricians should be informed of this serious complication.
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http://dx.doi.org/10.3109/23744235.2015.1122226DOI Listing
December 2016

Cervical Discitis in Children.

Pediatr Infect Dis J 2015 Jul;34(7):794-5

From the *Department of Pediatrics B, †Pediatric Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ‡Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; §Department of Imaging, and ¶Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Cervical discitis, though rare, should be included in the differential diagnosis of torticollis, neck pain and neurodevelopmental regression in motor skills in children and infants. Magnetic resonance imaging is the diagnostic method of choice. Treatment should be conservative with antibiotics only. The aim of this study was to describe the 10-year experience of a tertiary pediatric medical center with cervical discitis.
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http://dx.doi.org/10.1097/INF.0000000000000725DOI Listing
July 2015

Cholestatic Hepatitis Induced by Epstein-Barr Virus in a Pediatric Population.

Clin Pediatr (Phila) 2015 Oct 12;54(12):1153-7. Epub 2015 Feb 12.

Schneider Children's Medical Center of Israel, Petah Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: We present 5 cases of Epstein-Barr virus (EBV)-induced cholestatic hepatitis (CH) and review all additional pediatric cases from the literature.

Design: The medical records of 5 patients with EBV-induced CH were reviewed. A comprehensive review of the literature was performed.

Results: Including our patients, a total of 17 patients with EBV-induced CH were reviewed. The average age was 11 years (range 1-18 years); male to female ratio was 0.9:1. The most common presenting symptoms included fever, jaundice, and cervical lymphadenopathy. However, a significant number of patients presented with jaundice alone, without other suggestive signs of an EBV infection. Hepatocellular enzyme levels were significantly higher than in classical infectious mononucleosis. In many cases, serum alkaline phosphatase was also elevated, accompanied by direct hyperbilirubinemia.

Conclusion: EBV infection should be included in the differential diagnosis of CH in all age groups. In the vast majority, full recovery is expected.
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http://dx.doi.org/10.1177/0009922815570618DOI Listing
October 2015

Nosocomial respiratory syncytial virus infections in the palivizumab-prophylaxis era with implications regarding high-risk infants.

Am J Infect Control 2014 Sep;42(9):991-5

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

Background: Although respiratory syncytial virus (RSV) infection continues to be a leading cause of infant hospitalization with a high transmission rate, recent data on nosocomial RSV infection are scarce. This study investigated the clinical and epidemiologic characteristics of nosocomial RSV infection in the palivizumab-prophylaxis era.

Methods: The database of a tertiary pediatric medical center was searched for all hospitalized patients with RSV-positive respiratory disease in 2008-2010. Data were compared between patients with community-associated and nosocomial disease, and the qualification of the latter group for palivizumab was evaluated.

Results: Of the 873 children identified, 30 (3.4%) had a nosocomial infection. This group accounted for 0.06% of all admissions during the study period. The nosocomial infection group had higher rates of preterm birth and severe underlying disease than the community-associated RSV group and a longer mean hospital stay. The nosocomial infection group also had higher rates of intensive care unit admission and mechanical ventilation. Although 73% had underlying conditions, most (80%) did not qualify for RSV immunoprophylaxis, including 7 children (23%) with immune deficiency.

Conclusion: Nosocomial RSV infection is a significant cause of morbidity among hospitalized infants, especially those with comorbidities and lengthy hospital stay, and is associated with a complicated clinical course. In addition to strict infection-control measures, extending palivizumab prophylaxis to additional selected high-risk populations should be considered.
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http://dx.doi.org/10.1016/j.ajic.2014.05.030DOI Listing
September 2014
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