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We aimed to elucidate variables associated with coronavirus disease 2019 (COVID-19) vaccine compliance in adolescents and devise targeted interventions. Our secondary aim was to compare the rates of severe acute respiratory syndrome coronavirus 2 infection, hospitalizations and deaths between vaccinated and unvaccinated adolescents.A retrospective review of electronic medical records was performed on all adolescents 12-17 years of age registered at Clalit Health District in Israel during January 1, 2021, to November 18, 2021, with characterization by vaccination status against COVID-19. Univariate and multivariable analyses were employed to identify predictors of vaccination.Of the 43,919 subjects included in the study, 28,207 (64.2%) were vaccinated. Non-ultraorthodox Jewish adolescents had a higher vaccination rate than the minorities Arabs or ultraorthodox Jews (72.5%, 66.2% and 40.5%, respectively, Plt; 0.001). Adolescents of high socioeconomic status had nearly 2-fold higher vaccination rates than those of low socioeconomic status (80.4% vs 42.3%; Plt; 0.0001). Adolescents 16-17 years old had a higher rate of COVID-19 vaccination than those 12-15 years old (72.5% vs 60.6%, Plt; 0.001), as were girls versus boys (64.7% vs 63.8%, P = 0.047). Multivariate analysis identified 3 independent variables that were significantly ( Plt; 0.001) associated with low vaccination: ultraorthodox sector, Arab population, and underlying obesity (hazard rations 0.42, 0.72 and 0.84, respectively). Vaccination was significantly associated with reduced severe acute respiratory syndrome coronavirus 2 infection, hospitalization and death ( Plt; 0.001).This study highlights several pediatric populations with low COVID-19 vaccine compliance. Targeted interventions aimed at these populations are suggested with consideration of their special cultural, social and societal characteristics.

Shigella remains in the top four pathogens responsible for moderate to severe diarrhoea in children below 5 years of age. The shigella O-specific polysaccharide (O-SP) is a promising vaccine target. We developed a conjugate vaccine prototype incorporating a unique well defined synthetic oligosaccharide hapten, chemically designed for optimal antigenic, conformational, structural, and functional mimicry of the O-SP from Shigella flexneri 2a (SF2a). We aimed to assess the safety, tolerability, and immunogenicity of this original synthetic oligosaccharide-based vaccine candidate, SF2a-TT15, conceived to drive the antibody response towards the key protective determinants of the native lipopolysaccharide antigen, in a first-in-human phase 1 study.We did a first-in-human, dose-escalating, single-blind, observer-masked, randomised, placebo-controlled study at the Clinical Research Center of Tel Aviv Sourasky Medical Center (Israel). Participants were healthy adults aged 18-45 years with low titres of serum SF2a-specific IgG antibodies. 64 eligible participants were assigned to one of two cohorts. 32 participants in each of the two cohorts were randomly assigned via computer-generated algorithm in a stepwise manner to receive the 2 μg (cohort 1) and 10 μg oligosaccharide dose (cohort 2) of the SF2a-TT15 vaccine candidate non-adjuvanted or adjuvanted with aluminium hydroxide (alum) or matching placebos. The vaccine was administered as three single intramuscular injections into the arm, 28 days apart. The primary outcome was the incidence and severity of adverse events, which were assessed in the intention-to-treat safety population analysis including all participants who were randomly assigned and received at least one vaccine or placebo injection. The immunogenicity endpoints were secondary outcomes and were analysed in all participants who were randomly assigned, received all of the assigned injections before the time of the immunogenicity assessment, and provided blood samples for immunological follow-up (per-protocol immunogenicity analysis). The study is registered with ClinicalStudies.gov, NCT02797236 and is completed.Of 203 volunteers initially screened, 64 participants were enrolled between Sept 20, 2016, and Sept 26, 2017. In each of the two cohorts, 12 participants received the adjuvanted vaccine, 12 received the non-adjuvanted vaccine and eight received the matching placebo (four each). The SF2a-TT15 glycoconjugate was well tolerated at both doses. No serious or severe adverse events occurred. Overall, seven (88%) of eight to 12 (100%) of 12 in each group of volunteers had one adverse event or more after receiving the study agents with the majority of adverse events, 300 (98%) of 307, considered mild in intensity. Of the seven adverse events defined as moderate in severity, one (nausea) was suspected to be related to the vaccine candidate. At all post-immunisation days and for both oligosaccharide doses, whether adjuvanted or not, SF2a-TT15 induced significantly higher serum IgG anti-SF2a lipopolysaccharide geometric mean titres (GMTs) as compared with baseline or with the corresponding GMTs in placebo recipients (p0·01). After one injection, the non-adjuvanted 10 μg oligosaccharide dose induced a 27-times increase in IgG GMT (5080 vs 189) and the non-adjuvanted 2 μg oligosaccharide dose induced a five-times increase (1411 vs 283), compared with baseline. Alum enhanced the specific IgG response at 2 μg oligosaccharide dose after the third injection (GMTs 3200 vs 1176, p=0.045).SF2a-TT15 was safe and well tolerated and induced high titres of anti-SF2a LPS IgG antibodies. These results support further evaluation of this original synthetic oligosaccharide-protein conjugate vaccine candidate for safety, immunogenicity, and protective efficacy in target populations.The European Union Seventh Framework Programme.

Serum antibody levels to SARS-CoV-2 in infants born to mothers who had received 2 doses of the BNT2b2 vaccine during pregnancy correlated positively with increasing gestational age at vaccination (P < .01) and negatively with increasing time from vaccination (P < .01), with a significant drop in infants aged >60 days (P = .045).

Sentinel lymph node (SLN) biopsy is an integral part of treatment planning for a variety of cancers as it evaluates whether a tumor has metastasized, an event that significantly reduces survival probability. However, this invasive procedure is associated with patient morbidity, and misses small metastatic deposits, resulting in the removal of additional nodes for tumors with high metastatic probability despite a negative SLN biopsy. To prevent this over-treatment and its associated morbidities for patients that were truly negative, we propose a tissue oxygen imaging method called Photoacoustic Lifetime Imaging (PALI) as an alternative or supplementary tool for SLN biopsy. As the hyper-metabolic state of cancer cells significantly depresses tissue oxygenation compared to normal tissue even for small metastatic deposits, we hypothesize that PALI can sensitively and specifically detect metastases. Before this hypothesis is tested, however, PALI’s maximum imaging depth must be evaluated to determine the cancer types for which it is best suited. To evaluate imaging depth, we developed and simulated a phantom composed of tubing in a tissue-mimicking, optically scattering liquid. Our simulation and experimental results both show that PALI’s maximum imaging depth is 16 mm. As most lymph nodes are deeper than 16 mm, ways to improve imaging depth, such as directly delivering light to the node using penetrating optical fibers, must be explored.

Background Facing the global health crisis of COVID-19, health systems are increasingly supporting the use of telemedicine in ambulatory care settings. It is not clear whether the increased use of telemedicine will persist after the pandemic has resolved. The aims of this study were to assess the use of telemedicine by Israeli pediatricians before and during the first lockdown phase of the pandemic, and to elucidate how they foresee telemedicine as a medium of medical practice in the post-pandemic era. Methods A web-based survey was distributed among Israeli pediatricians in May 2020, soon after the end of first lockdown was announced. The survey assessed the frequency of telemedicine use as well as its influence on clinical decision making before and during the first COVID-19 lockdown, using two hypothetical clinical scenarios. The same scenarios were also used to assess how the pediatricians foresaw telemedicine in the post-pandemic period. In addition, administrative data from Maccabi on telemedicine use before, during and after the first lockdown were retrieved and analyzed. Results One hundred and sixty-nine pediatricians responded to the survey (response rate = 40%). The percentage of respondents who reported daily use of text messages, pictures and videoconferencing increased from 24, 15 and 1% before COVID-19 to 40, 40 and 12% during the lockdown, respectively (p p p p p Maccabi administrative data indicated that during the lockdown, there was an increase in phone visits and a decrease in in-person visits compared to the pre-lockdown levels of use. One month after the end of the first lock-down there was a partial return to baseline levels of in-person visits and a sustained increase in phone visits. Phone visits accounted for 0% of pediatrician visits before the first lockdown, 17% of them during the lockdown, and 19% of them 1 month after the lockdown relaxation. Conclusions The study indicates that use of telemedicine technologies by primary care pediatricians increased substantially during the first COVID-19 lockdown. The study also found that pediatricians expected that use levels will recede after the pandemic. As the pandemic continues and evolves, it will be important to continue to monitor the level of telemedicine use as well as expectations regarding post-pandemic use levels.

Background: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infection, with a high global health burden. There are no effective treatments available. ALX- 0171 is a novel trivalent Nanobody with antiviral properties against RSV. We aimed to assess the safety and antiviral activity of nebulised ALX- 0171 in children admitted to hospital with RSV lower respiratory tract infection. Methods: This double-blind, randomised, placebo- controlled, phase 2b trial was done in 50 hospital paediatric departments across 16 countries. Previously healthy children aged between 28 days to younger than 24 months who were admitted to hospital with RSV acute severe lower respiratory tract infection were randomly assigned in three sequential safety cohorts (3:1) to receive nebulised ALX-0171 (cohort 1 received 3 mg/kg, cohort 2 received 6 mg/kg, and cohort 3 received 9 mg/kg) or placebo once daily for 3 days using web- based randomisation in the sequential safety part (first block size 12, subsequently four). In a parallel part of the study, participants (cohort 4) were randomly assigned (parallel 1:1:1:1) to receive nebulised ALX-0171 3 mg/kg, 6 mg/kg, 9 mg/kg, or placebo (blocks of eight by restricted randomisation). Study drug masking was by two consecutive nebulisations (each either ALX-0171 or placebo) depending on assigned treatment group. The primary outcome was to evaluate time for the RSV viral load to drop to below quantifiable limit, measured by plaque assay on mid-turbinate nasal swabs. Safety, clinical efficacy, pharmacokinetics, viral load by RT-qPCR, and immunogenicity were secondary outcomes. Analysis, including of the primary outcome, was by modified intention to treat (participants receiving at least one dose of study drug as assigned), and safety was assessed in all children who received at least one administration of study drug, as treated. This trial is registered with EudraCT, 2016-001651-49. Findings: Between Jan 10, 2017, and April 26, 2018, 175 children (median age 4·8 months [IQR 2·0-10·8]), received at least one dose of study drug (45 received 3 mg/kg of ALX-0171, 43 received 6 mg/kg of ALX-0171, 45 received 9 mg/kg of ALX- 0171, and 42 received placebo ; the modified intention-to-treat population) commencing at a mean 3·3 days (SD 1·1) from symptom onset. Median time for the viral load to drop to below quantifiable limit on plaque assay was significantly faster for the 3 mg/kg group (median 14·2 h [IQR 5·0-28·0]), 6 mg/kg group (5·1 h [4·7- 28·5]), and 9 mg/kg group (5·1 h [4·6-5·9]) than the placebo group (46·1 h [25·2-116·7] ; hazard ratio [HR] all ALX-0171 groups vs placebo 2·6 [1·7-3·9] ; p92% for 4 h in room air and adequate oral feeding) in ALX-0171 groups and the placebo group (median 43·8 h [IQR 21·7-68·5] vs 47·9 h [22·5-76·4] ; HR 1·1 [95% CI 0·8-1·6]) or change in the global severity score from baseline to 5 h post-dose on day 2 (-4 [IQR -6 to -2] vs -4 [-6 to -1] ; difference in least- squares mean -0·45 [95% CI -1·39 to 0·49]). Serum concentrations of ALX-0171 on day 2 exceeded the concentration estimated to give full RSV neutralisation in the lung at 6 mg/kg and 9 mg/kg doses. Treatment-emergent antidrug antibodies were detected at day 14 in 46 (34%) of 135 patients who received ALX-0171 and ten (26%) of 39 patients who received placebo. Serious adverse events were reported in five (13%) of 40 children in the placebo group and ten (7%) of 135 children in all ALX-0171 groups, leading to study drug discontinuation in three children (two in the 3 mg/kg group and one in the 6 mg/kg group). 13 of 15 serious adverse events (three of four in the 3 mg/kg group, two of three in the 6 mg/kg group, three of three in the 9 mg/kg group, and five of five in the placebo group) were related to worsening respiratory status, and none were considered to be related to the study drug. Interpretation: Antivirals against RSV might be unable to improve clinical course once RSV lower respiratory tract infection is established. Future studies of RSV antivirals should focus on earlier intervention and more precise measurement of objective outcomes before the onset of significant lower respiratory tract inflammation.

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

Aim This study evaluated the effectiveness of three different treatments for bronchiolitis in a tertiary pediatric 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 days and 3.8 days) were significantly lower than Ward A (2.8 days and 5.3 days) and Ward B, (2.9 days and 4.7 days) where nebulised hypertonic saline was given more frequently (38.7% to 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. This article is protected by copyright. All rights reserved.

Respiratory syncytial virus (RSV)-related bronchiolitis is a common cause of morbidity in young infants. The recommendations for its passive prevention by palivizumab are currently under intensive debate.To elucidate the optimal prevention strategy by studying the morbidity of RSV disease under the current recommendations for palivizumab prophylaxis in Israel.We collected demographic and clinical data of all children hospitalized with microbiologically confirmed RSV bronchiolitis during 2015-2016 at Schneider Children's Medical Center. The seasonality of RSV disease was also studied for the period 2010-2017 in sentinel clinics scattered throughout Israel.Of the 426 hospitalized children, 106 (25%) had underlying diseases but were not eligible for palivizumab prophylaxis according to the current criteria in Israel. Their course was severe, with a mean hospital stay of 6.7 days and a 12% admission rate to the pediatric intensive care unit (PICU). Palivizumab-eligible children who did not receive the prophylaxis before hospitalization had the most severe course, with 22% admitted to the PICU. More children were diagnosed with RSV disease in October than in March among both hospitalized and ambulatory children; 44% of the palivizumab-eligible hospitalized children were admitted in the last 2 weeks of October, before 1 November which is the recommended date for starting palivizumab administration in Israel.According to the results of the present study we suggest advancing RSV prophylaxis in Israel from 1 November to mid-October. The precise palivizumab-eligible categories should be reconsidered.

Physician burnout and depression have been recognized as serious international problems and the secondary costs of poor physician mental health are substantial. Interventions to address this problem can be split into two categories: those focusing on the individual, and those addressing the work environment. Individual-focused programs often include instruction in mindfulness, nutrition, and exercise, while those in the work environment have focused largely on stressors such as administrative burden, electronic health records, and productivity pressures. The recent IJHPR article entitled “Burnout and intentions to quit the practice among community pediatricians: Associations with specific professional activities”, by Grosman et al., offers an additional path to address burnout and well-being in pediatricians through increasing of hours in more satisfying professional activities. While “satisfaction” was the metric in this study, what lay at the root of that satisfaction may be deeper and more profound. What the study does not measure is that the less-burned out physicians who felt greater satisfaction may have also felt a greater sense of meaning in their lives. Grossman et al. rightly urge health care managers to encourage diversification of the pediatrician’s job by enabling greater engagement in the identified ‘anti- burnout’ professional activities, however more can and should be done. Physicians themselves should take an active role in both the seeking of, and connection to, meaning. Burnout and frustration, understandably, may have led some doctors to possess a sense of cynicism that has obscured meaning in their lives. If physicians cannot find a path to meaning on their own, they should seek colleague partners, coaches, or therapists to assist. Physicians can advocate for programs to reduce work-force stressors, but they can also advocate for formal programs such as Healers Arts programs, Schwartz rounds, and narrative medicine programs to help reconnect to meaning in their daily clinical work. Brief courses in cognitive behavioral techniques may also help in combating problematic mindsets endemic in medicine such as negativity bias, maladaptive perfectionism, and pessimistic explanatory style. With effort, a growth mindset, and when needed, guidance and some reinforcement, these negative and toxic mindsets can diminish; they can fade, and further open physicians to the healing power of meaning.

Background Vaccines are one of the most important achievements of modern medicine. However, their acceptance is only partial, with vaccine hesitancy and refusal representing a major health threat. Influenza vaccines have low compliance since repeated, annual vaccination is required. Influenza vaccines stimulate discussions both in the real world and online. Social media is currently a significant source of health and medical information. Elucidating the association between social media engagement and influenza vaccination is important and may be applicable to other vaccines, including ones against COVID-19. Objective The goal of this study is to characterize profiles of social media engagement regarding the influenza vaccine and their association with knowledge and compliance in order to support improvement of future web-associated vaccination campaigns. Methods A weblink to an online survey in Hebrew was disseminated over social media and messaging platforms. The survey answers were collected during April 2020. Anonymous and volunteer participants aged 21 years and over answered 30 questions related to sociodemographics; social media usage; influenza- and vaccine-related knowledge and behavior; health-related information searching, its reliability, and its influence; and COVID-19-related information searching. A univariate descriptive data analysis was performed, followed by multivariate analysis via building a decision tree to define the most important attributes associated with vaccination compliance. Results A total of 213 subjects responded to the survey, of whom 207 were included in the analysis; the majority of the respondents were female, were aged 21 to 40 years, had 1 to 2 children, lived in central Israel, were secular Israeli natives, had higher education, and had a salary close to the national average. Most respondents (128/207, 61.8%) were not vaccinated against influenza in 2019 and used social media. Participants that used social media were younger, secular, and living in high-density agglomerations and had lower influenza vaccination rates. The perceived influence and reliability of the information on social media about COVID-19 were generally similar to those perceptions about influenza. Conclusions Using social media is negatively linked to compliance with seasonal influenza vaccination in this study. A high proportion of noncompliant individuals can lead to increased consumption of health care services and can, therefore, overload these health services. This is particularly crucial with a concomitant outbreak, such as COVID-19. Health care professionals should use improved and targeted health communication campaigns with the aid of experts in social media. Targeted communication, based on sociodemographic factors and personalized social media usage, might increase influenza vaccination rates and compliance with other vaccines as well.

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

The number of children accompanying their parents in international travel is increasing steadily, and with the rising global migration, children more frequently accompany their parents or caregivers for visiting friends or relatives (VFR). As compared to travel for tourism, VFR children are at higher risk of acquiring local diseases, as they more often stay in rural areas in resource-poor locations, have longer periods of visit, are less likely to attend pre-travel consultations, and less frequently adhere to recommended precautions. Travelers's diarrhea (TD) is the most common travel-associated illnesses in children. This review updates the existing knowledge on TD in children, regarding its distinctive epidemiology, risk factors, preventive measures, clinical manifestations, complications, causative microorganisms and management. Despite the limited focused research on pediatric TD, which challenges the formulation of children-oriented evidence-based guidelines, practical recommendations are suggested.

Aims This study aimed to evaluate the use of the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) among children admitted in a paediatric hospital, and assess its impact on the nutritional status awareness among the medical staff and on health outcomes at discharge. Methods STAMP performed by nurses on admission was compared with full nutritional assessment performed by a dietitian. Area under the receiving operating characteristic (AUROC) curve was used to evaluate validity of the tool. To assess how the tool affected awareness among the staff, information on nutritional status was compared prior to and following the intervention period. Therewith, health outcomes at discharge were compared for the children who had been screened by STAMP and the children who had not. Results The analysis was performed for a total of 60 children (38 boys, 63%). The mean age was 7.8 ± 4.7 years. Malnutrition was found in 16% of patients, segregating equally between acute and chronic malnutrition. Sensitivity, specificity, positive predictive value and negative predictive value were 95.7% (95% confidence interval, CI = 85.75-98.83%), 76.9% (95% CI = 49.74-91.82%), 93.7 and 83.3, respectively. AUROC was 0.863 (95% CI = 0.72-1). There was no difference either in malnutrition awareness among the medical staff before and after the intervention period or in health outcomes at discharge. Conclusions STAMP is a valid tool for malnutrition screening in hospitalised children; however, its use does not influence admitted patients' nutritional status awareness among the medical staff nor their outcomes at discharge.

Leukemoid reaction (WBC 30,000/μL) may indicate significant medical conditions, mostly infectious. Prompted by the lack of population-based data on the presentation, characteristics, and necessary workup in children with leukemoid reaction, we searched the database of a tertiary pediatric medical center for all children presented with at least one WBC count of ≥ 30,000/μL in 2009-2014. Demographic, clinical, and laboratory parameters were recorded. Children admitted with WBC 30,000/μL served as controls. Pneumonia was the most common diagnosis in the leukemoid reaction group, with a 5.5-fold higher prevalence of pleuropneumonia than in the control group. The leukemoid group had a longer average hospital stay (7.5 vs. 5.5 days). Patients with WBC ≥ 50,000/μL had a sixfold higher rate of leukemia than patients with a lower count. There was a significant association of leukemia with low platelet count, low levels of C-reactive protein, and high levels of uric acid and lactate dehydrogenase.Children presented with a leukemoid reaction are at high risk of pneumonia, especially pleuropneumonia, and a long hospital stay. Those with WBC ≥ 50,000/μL have a sixfold higher risk of leukemia. For prompt diagnosis, clinicians should be aware of the variables associated with leukemia. What is Known: • Leukemoid reaction has been associated with infectious diseases. • Leukemoid reaction at presentation in adults is correlated with high morbidity and mortality. What is New: • Children with leukemoid reaction are at high risk of pleuropneumonia. • We did not observe increased mortality in children with a leukemoid reaction.

Shigella flexneri (S. flexneri) 6 has emerged as an important cause of shigellosis. Our efficacy study of Shigella sonnei and S. flexneri 2a O-specific polysaccharide (O-SP) conjugates in 1–4 year-olds had too few S. flexneri 2a cases for efficacy evaluation but surprisingly showed protection of 3–4 year-olds, S. flexneri 2a-recipients, from S. flexneri 6 infection. To investigate this cross-protection antibodies to both Shigella types were investigated in all sera remaining from previous studies. Twenty to 30% of 3–44 year-old humans injected with S. flexneri 2a conjugate responded with ≥4-fold increases of IgG anti type 6, p < 0.00001. The specificity of these antibodies was shown by inhibition studies. S. flexneri 6 infection of 2 children induced besides S. flexneri 6, also S. flexneri 2a antibodies, at levels of S. flexneri 2a vaccinees. S. flexneri 2a antibodies induced by S. flexneri 6 conjugates could not be studied since no such conjugate was assessed in humans and mice responded almost exclusively to the O-SP of the injected conjugate, with no cross-reactive antibodies. Our results indicate induction of cross-reactive protective antibodies. The O-acetylated disaccharide shared by S. flexneri 6 and 2a O-SPs, is the likely basis for their cross-reactivity. S. flexneri 6 O-SP conjugates, alone and in combination with S. flexneri 2a, merit further investigation for broad S. flexneri protection.

Background The aim of this open-label, active-controlled, parallel group, phase 2 follow-up study was to assess the long-term immunogenicity of Epaxal Junior, the pediatric dose of an aluminum-free virosomal inactivated hepatitis A virus (HAV) vaccine, in children receiving routine childhood vaccines (RCV). Methods Healthy children (12-15 months old, ≥8 kg weight) were randomized (1:1:1) to group A: Epaxal Junior + RCV (day 1); group B: Epaxal Junior (day 1) + RCV (day 29) and group C: Havrix 720 + RCV (day 1). All 3 groups received 2 doses of HAV vaccines 6 months apart. Children who completed the primary study were followed up from 18 months to 7.5 years post booster. Results Of 291/327 randomized children who had completed the primary study, 157 were followed for the 7.5-year analysis (group A: 50; group B: 54; and group C: 53). Of these, 152 children had protective levels of anti-HAV antibodies [≥10 mIU/mL; 98% (group A); 96.3% (group B); 96.2% (group C)]. Anti-HAV geometric mean concentrations were similar in groups A and B at all the time points (1.5-, 2.5-, 3.5-, 5.25- and 7.5-year time point) but slightly lower in group C. Predictions of the median duration of persistence of seroprotective antibody levels, using the linear mixed model were similar in all groups: (group A: 19.1 years, group B: 18.7 years, group C: 17.3 years). Conclusions Immunization with Epaxal Junior administered with RCVs at 12 months elicited protective response beyond 7.5 years in almost all children. Assessing the kinetic of anti-HAV antibody titers decline over time, the moment to reach antibody concentrations below the accepted protective level may occur earlier than previously estimated.

Background: Infective endocarditis (IE) in children is continuously changing in regard to underlying conditions, predisposing factors, etiologic agents, clinical manifestations, treatment, and outcome. We describe current characteristics and compare healthcare-associated and community-associated disease. Patients and Methods: All children (

This study sought to expand current knowledge on the clinical and epidemiological characteristics of persistent coagulase-negative Staphylococcus (CoNS) bacteremia in very-low-birth-weight (VLBW) infants. Background and disease-related data were collected prospectively on 143 VLBW infants diagnosed with CoNS bacteremia at a pediatric tertiary medical center in 1995-2003. Findings were compared between those with persistent (positive blood cultures for72 h under appropriate treatment ) and nonpersistent disease. Fifty-eight infants (40.6%) were found to have persistent bacteremia. There were no between-group differences in maternal characteristics, mode of delivery, newborn characteristics, dwell time of central venous and umbilical catheters, complications of prematurity, or mean hospital stay. The persistent bacteremia group had significantly higher rates of hypothermia at presentation (37.9% vs. 17.6%, p 0.04), creatinine1.2 mg% on treatment day 7 (13.7% vs. 2.4%, p 0.02; transient phenomenon), and endocarditis (p 0.03); one infant had an aortic thrombus. Predominantly breast-fed infants had a higher rate of negative cultures within 72 h of appropriate treatment than predominantly formula-fed infants (60% vs. 19%, p 0.02). In conclusion, persistence of CoNS bacteremia is common in VLBW infants. Endocarditis should be excluded in all infants with persistent disease. Breast-feeding is associated with a shorter disease duration.

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.

Data on the risk factors for typhlitis in children with cancer are limited. The aim of the study was to define the epidemiologic and clinical features of typhlitis and to elucidate predisposing factors for its development. The medical records of pediatric patients with cancer who were diagnosed with typhlitis from 1995 to 2005 were reviewed for clinical, laboratory, and imaging findings. The results were compared with a group of patients with cancer but without typhlitis who were hospitalized during the same period. Of the 843 cancer patients, 42 (5%) had episodes of typhlitis; 32 of them (76%) were being treated for hematologic malignancies. The incidence was highest in patients with Burkitt's lymphoma (15%) and acute myeloblastic leukemia (12%). Work-up included abdominal x-ray in all patients; abdominal ultrasonography and computed tomography were performed in 23% and 11% of patients, respectively. No cases were missed by plain x-ray when compared with computed tomography and ultrasonography. The typhlitis was treated without surgery and survival was 100%. On multivariate analysis, mucositis [odds ratio (OR) = 30.7], stem cell transplantation (OR = 58.9), and receipt of chemotherapy in the previous 2 weeks (OR = 12.9) were significantly associated with the occurrence of typhlitis. We conclude that most children with typhlitis may be treated without surgery in most cases with favorable outcome. A high index of suspicion may be warranted in patients after stem cell transplantation or chemotherapy and patients with mucositis.

We describe an outbreak of bloodstream infections due to Mycobacterium mucogenicum involving five patients in a paediatric haematology-oncology ward over a six-month period. Specimens from faucets on the floor indicated that an automatic faucet was the probable source of infection and identity between strains was confirmed using molecular techniques. Levels of chlorine in the water were intermittently low and may have contributed towards bacterial growth. A review of infection control practices revealed that the exit sites of central venous catheters (CVCs) of children were not properly covered during bathing, which may have facilitated CVC colonisation. Replacing the contaminated faucets, optimal water chlorination and proper coverage of the CVC exit site using impermeable dressings terminated the outbreak. This investigation emphasises the three major factors that should be investigated in outbreaks due to a waterborne pathogen: source of the infection, water supply and infection control practices.

Summary. For many years hepatitis A was one of the most common vaccine preventable diseases in Israel. In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objectives of the present study were to study trends in disease incidence after the implementation of the new vaccination policy and to assess vaccination coverage among children and adults in Israel. We used the databases of the second largest HMO in Israel (1.7 million members) to identify patients who had evidence of hepatitis A in 1998 and 2007 and to collect information on all subjects who received at least one dose of hepatitis A vaccine during the study period. Hepatitis A vaccination coverage in children

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

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.To evaluate the distribution of CRP levels in children with primary herpetic gingivostomatitis.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.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.High values of CRP are prevalent in patients with primary herpetic gingivostomatitis, similar to adenoviral infections and some bacterial infections.

Young children have a high incidence of influenza and influenza-related complications. This study compared the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) with trivalent inactivated influenza vaccine (TIV) in young children with a history of recurrent respiratory tract infections (RTIs).Children 6 to 71 months of age were randomized to receive 2 doses of CAIV-T (n = 1101) or TIV (n = 1086), 35 +/- 7 days apart before the start of the 2002-2003 influenza season and were followed up for culture-confirmed influenza, effectiveness outcomes, reactogenicity, and adverse events.Overall, 52.7% (95% confidence interval [CI] = 21.6%-72.2%) fewer cases of influenza caused by virus strains antigenically similar to vaccine were observed in CAIV-T than in TIV recipients. Greater relative efficacy for CAIV-T was observed for the antigenically similar A/H1N1 (100.0%; 95% CI = 42.3%-100.0%) and B (68.0%; 95% CI = 37.3%-84.8%) strains but not for the antigenically similar A/H3N2 strains (-97.1%; 95% CI = -540.2% to 31.5%). Relative to TIV, CAIV-T reduced the number of RTI-related healthcare provider visits by 8.9% (90% CI = 1.5%-15.8%) and missed days of school, kindergarten, or day care by 16.2% (90% CI = 10.4%-21.6%). Rhinitis and rhinorrhea, otitis media, and decreased appetite were the only events that were reported more frequently in CAIV-T subjects. There was no difference between groups in the incidence of wheezing after vaccination.CAIV-T was well tolerated in these children with RTIs and demonstrated superior relative efficacy compared with TIV in preventing influenza illness.

Background Currently hospitalization for children with urinary tract infections (UTIs) is reserved for severe or complicated cases. Changes may have taken place in the characteristics and causative uropathogens of hospital-treated community-acquired UTI. Objectives To study children hospitalized in a tertiary center with community-acquired UTI, compare Escherichia coli and non-E. coli UTI, define predictors for non-E. coli UTI and elucidate the appropriate therapeutic approach. Patients and methods A prospective clinical and laboratory study from 2001 through 2002 in a tertiary pediatric medical center. Patients were divided by results of the urine culture into E. coli and non-E. coli UTI groups, which were compared. Results Of 175 episodes of culture-proved UTI, 70 (40%) were caused by non-E. coli pathogens. Non-E. coli UTI was more commonly found in children who were male (P = 0.005), who had underlying renal abnormalities (P = 0.0085) and who had received antibiotic therapy in the prior month (P = 0.0009). Non-E. coli uropathogens were often resistant to antibiotics usually recommended for initial therapy for UTI, including cephalosporins and aminoglycosides; 19% were initially treated with inappropriate empiric intravenous antibiotics (compared with 2% for E. coli UTI, P = 0.0001), with a longer hospitalization. Conclusions Current treatment routines are often inappropriate for hospitalized children with non-E. coli UTI, which is relatively common in this population. The defined risk factors associated with non-E. coli UTIs and its antimicrobial resistance patterns should be considered to improve empiric antibiotic therapy for these infections.

This study highlights the less common presentations of Hirschsprung disease (HD) and HD-associated enterocolitis (HAE) in neonates and infants. We present three infants whose diagnosis was delayed because of atypical presenting features, especially with failure to gain weight, decreased appetite, episodes of diarrhoea and vomiting and hypoalbuminaemia. The reported incidence of HAE ranges from 0 to 16.2%. To avoid complications of life-threatening HAE, primary care physicians require a high index of suspicion of the more unusual presentations of HD in neonates and infants.

Objective: To determine the serum nitric oxide levels in healthy neonates and in infants with bacteremia. Methods: We performed a prospective study in a tertiary neonatal intensive care unit. The serum nitric oxide levels were measured in all infants at birth (basal) and in the infected neonates also on the first 2 days of bacteremia. Results: Thirty-three neonates (10 term, 23 preterm) were included. Eleven preterm infants (mean gestational age 27 weeks) had bacteremia. The main blood culture isolates included coagulase-negative staphylococci (n = 4), Klebsiella pneumoniae (n = 3), and Escherichia coli (n = 3). The serum nitric oxide levels increased during infection in 10 infants (p < 0.008). The mean nitric oxide level before infection was 44 µM and during infection 96 µM (p = 0.008). In the healthy babies, the mean nitric oxide level was 26 µM in those with a gestational age M in those born between 28 and 36 weeks of gestation, and 63 µM in term infants. Conclusions: Bacteremic preterm infants produce significantly higher amounts of nitric oxide. The basal nitric oxide levels at birth may be correlated with gestational age.

Hospital and community-clinic workers were tested for hepatitis A virus antibodies (HAV)-IgG to identify variables associated with presence of (HAV-IgG) and to determine whether sociodemographic background may explain all differences in HAV seropositivty among healthcare workers. Logistic regression analysis was used to identify variable associated with HAV-immunity. Multivariate logistic regression analysis revealed that HAV-seroprevalence correlated significantly (P0.01) with age, siblings, residence in rural areas and origin. Nurse aides had an increased risk for HAV seropositivity (OR=5.04; 95% CI: 1.49-17.08) whereas physicians had a lower risk (OR=0.54: 95% CI: 0.30-0.98). Age and socioeconomic background were independently correlated with HAV immunity but did not explain all difference in HAV-seroprevalence. The higher susceptibility and elevated incidence of hepatitis A amongst physicians, prioritize primary prevention in this group.

Hepatitis A is an important infectious disease in Israel. The high incidence of hepatitis A, the declining prevalence of antibodies against hepatitis A virus throughout the past decade, and the availability of an active immunization for hepatitis A have engendered the identification of occupations in which workers are at increased risk of acquiring the disease. A prevalence study for hepatitis A antibodies was conducted during the first half of 1998 in a random sample of 37 day-care centers in different parts of Israel. A short interview was conducted, and serum samples were then collected from each worker. The control group comprised a sample of factory workers, blood donors, and women in maternity wards. Ninety percent (402 of 446) of the day-care workers had antibodies to hepatitis A. In a logistic-regression analysis, seropositivity was associated with increased age, minimal education, and lack of military service. When the authors compared a subsample of workers aged 18-40 yr with the control group, seropositivity was associated with the following: birth in Israel, duration of residence in Israel, very minimal education, military service, and employment in a day-care center. These results, together with earlier reports, indicate that day-care workers are at high risk of occupational exposure to hepatitis A. These results may imply that seronegative workers have a 2-fold chance of acquiring hepatitis A. Appropriate preventive measures should be considered, and active immunization of susceptible workers should be undertaken.

To determine the impact of early surgical intervention on long-term survival in patients with infective endocarditis (IE), charts of all patients who had IE from January 1987 through December 1996 were reviewed. A total of 252 patients with definite or possible IE were included. Forty-four patients (17.5%) had early surgery on median hospital day 2 (range, 0‐30 days), and 208 patients (82.5%) received medical treatment alone. On multivariate analysis, several variables, including early surgical intervention, improved long-term survival rates (hazard ratio, 1.5; ), mainly in patients with Staphylococcus aureus etiology ( ). When patients P p .03 P p .04 with prosthetic devices were excluded, the median duration of survival for patients who had early surgery was 1150 months, compared with 61.5 months for patients in the medical group ( ). Early surgical P p .1 intervention compared with medical therapy alone is associated with increased short- and long-term survival rates in patients with IE, primarily when IE is caused by S. aureus. In the era before antibiotics, infective endocarditis (IE) was always fatal. More than 50 years after the introduction of antibiotic therapy, and more than 30 years after the first successful valve replacement, the reported early mortality rate of IE remains considerable (14%‐ 31%), and late mortality rates after 5-year follow-up range from 25% to 60% [1‐4]. Only a few large series on the long-term outcome of patients with IE have been reported, and even fewer have studied the impact of early surgery on long-term outcome [1, 5‐16]. The purposes of the present study were to determine long-term survival rates after an episode of IE, to delineate risk factors for mortality, and to focus on the impact of surgery performed during the active phase of IE on the long-term survival rate.

Optimal treatment of acute bronchiolitis is currently unclear. In a double-blind study, we found no significant differences between inhaled epinephrine and nasal decongestant in hospitalized infants with acute bronchiolitis regarding length of hospitalization, need for oxygen supplementation, or intravenous fluids and clinical score. Nasal decongestant is as effective as inhaled epinephrine in acute bronchiolitis.

In this 1 year cross-sectional study of personnel being discharged from compulsory military service, an available database of health-related information was used to examine the association of meningococcal carriage with socio-demographic factors. A representative, systematic sample of 1632 personnel was interviewed and had throat cultures taken. The overall meningococcal carriage rate was 16%. Serogroups B and Y accounted for 76% and 13% of the isolates respectively. In univariate analysis, carriage was associated with male gender (PP=0·002), smoking (P=0·014), and service at a ‘closed’ base, reflecting greater interpersonal contact (P

The database of a major microbiology laboratory in Israel was searched to determine the prevalence of nontuberculous mycobacterial lymphadenitis in immunocompetent children. We observed a 4-fold increase in nontuberculous mycobacteria isolates during 1985–2006, which was attributable mainly to increased detection of Mycobacterium haemophilum starting in 1996.

Some studies have demonstrated that in infective endocar-ditis (IE) older age is associated with a higher mortality rate[1, 2], higher frequency of mitral-valve involvement [3],renal failure, and cerebral embolism [4]. In the studypresented here, we aimed to analyze the clinical features ofIE and to delineate short- and long-term outcome of IE inchildren, young adults and elderly patients. Charts of allpatients definitively diagnosed with IE from January 1987through December 1996 were identified (n=228) andgrouped according to age: group I included patients aged1–15 years; group II, patients aged 16–40 years; group III,patients aged 41–60 years; and group IV, patients aged≥61 years. For each patient, data on demographics, clinicalfeatures, and outcome were collected. Statistical analyseswere performed using ANOVA, chi-square, and Coxregression for multivariable analysis of survival (SPSSCorporation, Chicago, IL, USA).None of the 228 patients analyzed had a history ofintravenous drug abuse. There were 13 patients in group I,25 in group II, 57 in group III, and 133 in group IV. Nosignificant differences in clinical symptoms, rate of surgicalintervention, and length of hospitalization were foundamong the groups (Table 1). As expected, congenital heartanomalies were common (62%) in group I, while native-valve involvement (rheumatic and degenerative heartdisease) was more frequent in the other groups (40% ingroup II and 47% in groups III and IV; p=0.001).Prosthetic-valve IE occurred more commonly in groups IIand III (36 and 32%, respectively) than in groups I (8%)and IV (16%) (p

Full-time work has long been perceived as a cornerstone of medical residency, the consensus being that a resident must apply the bulk of his time and attention to his professional training. Demographic and cultural changes that have taken place over the last several years, specifically the rise in the number of female doctors and the importance of leisure time to the younger generation, have intensified the need to find new and innovative ways to deal with the plight of the resident population. One idea, already in effect in many Western countries, is the institution of part-time residency programs. The possibility of fulfilling residency requirements on a part-time basis is intended to assist medical residents in integrating their professional development with their personal and family life, without compromising the quality of their training. A number of research studies conducted over the last several years in countries that allow part-time residency, among them the United States, England and Switzerland, aimed to examine the quality of part-time training. The various studies evinced a high level of satisfaction from the program both by the residents themselves and their supervisors, and in many aspects those doing residency part-time received higher appraisals than their full-time colleagues. Some of the residents polled noted that they would have totally foregone the practice of medicine had there not been an option to complete residency part-time. In light of the experience throughout the world and the changing landscape in Israel, the Scientific Council of the Israeli Medical Association decided to examine the issue and its various aspects, and weighed all the considerations in favor and against part-time residency. Recently, the Scientific Council approved the launch of a pilot program to allow part-time residency in several fields that were carefully selected according to specific criteria. Once the Ministry of Health completes the LegisLation process, part-time residency will officially begin in Israel.

Structural heart disease, intravascular catheters, and invasive procedures are predisposing factors for infective endocarditis (IE). Data on IE in children with structurally normal hearts and no predisposing factors are limited. We aim to characterize IE (definite or possible by Duke criteria) in such a subgroup of pediatric patients (age

Vancomycin is widely used to treat late onset coagulase-negative Staphylococcus (CoNS) sepsis in very low birth weight (VLBW) infants. Although vancomycin is associated with a risk of toxicity and bacterial resistance, the appropriate duration of use has not been established. This study sought to investigate the association between the duration of vancomycin therapy and clinical outcome in VLBW infants with CoNS sepsis.The files of all VLBW infants treated for CoNS sepsis at a tertiary paediatric medical centre from 1995-2003 were reviewed for clinical data, laboratory variables and outcome. Only patients with two positive diagnostic blood cultures were included. The findings were analyzed by duration of vancomycin treatment after the last positive blood culture.The study cohort included 126 infants, 48 treated for 5 days, 32 for 6-7 days, 31 for 8-10 days and 15 for10 days. There were no differences among the groups in perinatal characteristics, central catheter dwell time, laboratory data including haematologic, renal and liver function tests, or rate of complications of prematurity. Five infants were diagnosed with infective endocarditis or aortic thrombi and were treated for10 days. CoNS sepsis recurred in two infants (1.6%). No toxicity of vancomycin treatment was observed.In VLBW infants with uncomplicated CoNS sepsis, treatment with vancomycin for 5 days after the last positive blood culture appears to be associated with a satisfactory outcome and no adverse effects. A well-controlled prospective multicentre study is needed to confirm these findings.

Reported here is a retrospective molecular analysis of the isolates recovered from the first outbreak of nalidixic acid (NA)-resistant Shigella sonnei shigellosis to occur in Israel. The outbreak affected 94 children. In the retrospective analysis, a total of 13 NA-resistant isolates and five NA-susceptible isolates recovered during the outbreak period were examined. Restriction fragment length polymorphism profiles obtained by digestion with BamHI, PvuI, HinfI or SmaI yielded identical profiles for all 18 isolates. All NA-resistant strains had an identical plasmid profile, but this profile differed from that displayed by the susceptible strains. In all of the NA-resistant strains a 304 bp fragment in the gyrA gene coding for a region associated with NA resistance was sequenced and showed a single point mutation, Ser83--Phe. In this outbreak, the isolates of NA-resistant Shigella sonnei belonged to a single clone and NA resistance was associated with a point mutation in the gyrA gene.

Received November 20, 2009, Received Revised August 18, 2010, Submitted August 19, 2010 Fever after cardiac surgery in children may be due to bacterial infection or noninfectious origin like systemic inflammatory response syndrome (SIRS) secondary to bypass procedure. A marker to distinguish bacterial from nonbacterial fever in these conditions is clinically important. The purpose of our study was to evaluate, in the early postcardiac surgery period, whether serial measurement of C-reactive protein (CRP) and its change over time (CRP velocity) can assist in detecting bacterial infection. A series of consecutive children who underwent cardiac surgery with bypass were tested for serum levels of CRP at several points up to 5 days postoperatively and during febrile episodes (>38.0°C). Findings were compared among febrile patients with proven bacterial infection (FWI group; sepsis, pneumonia, urinary tract infection, deep wound infection), febrile patients without bacterial infection (FNI group), and patients without fever (NF group). In all, 121 children were enrolled in the study, 31 in the FWI group, 42 in the FNI group, and 48 patients in the NF group. Ages ranged from 4 days to 17.8 years (median 19.0, mean 46 ± 56 months). There was no significant difference among the groups in mean CRP level before surgery, 1 hour, and 18 hours after. A highly significant interaction was found in the change in CRP over time by FWI group compared with FNI group ( P < .001). Mean CRP velocity ([fCRP – 18hCRP]/[fever time (days) – 0.75 day]) was significantly higher in the infectious group (4.0 ± 4.2 mg/dL per d) than in the fever-only group (0.60 ± 1.6 mg/dL per d; P < .001). A CRP velocity of 4 mg/dL per d had a positive predictive value (PPV) of 85.7% for bacterial infection with 95.2% specificity. Serial measurements of CRP/CRP velocity after cardiac surgery in children may assist clinicians in differentiating postoperative fever due to bacterial infection from fever due to noninfectious origin.

The objectives of this study were to characterize community-acquired (CA) enterococcal urinary tract infections (UTIs) in a tertiary pediatric center and to determine risk factors for their occurrence, their association with renal abnormalities, their antibiotic susceptibility profile, and the appropriateness of the empiric antibiotic treatment, in comparison to those of Gram-negative UTIs. In a 5-year prospective clinical and laboratory study, we found that enterococcal UTIs caused 6.2% (22/355) of culture-proven CA UTIs. Compared with Gram-negative UTI, enterococcal UTI was associated with male predominance, higher rates of underlying urinary abnormalities (70 vs. 43.7%; p = 0.03) and inappropriate empiric antibiotic therapy (22 vs. 5.6%; p = 0.02), and mainly vesicoureteral reflux (53% of cases). This study highlights the importance of early detection of CA enterococcal UTIs because of their association with underlying urinary abnormalities and a high rate of inappropriate empiric antibiotic therapy. Renal imaging is recommended for children with enterococcal UTIs; Gram stain is suggested in selected cases to detect Gram-positive cocci for early diagnosis of enterococcal UTIs and initiation of appropriate antibiotics.

Purpose The aim of the present study was to determine if blood procalcitonin can serve as an aid to differentiate between bacterial and nonbacterial cause of fever in children after cardiac surgery. Materials and Methods A nested case-control study of children who underwent open cardiac surgery in critical care units of fourth-level pediatric hospital was performed. Blood samples for procalcitonin level were collected 1 day before operation; 1 hour postoperation; on postoperative days 1, 2, and 5; and on the day of fever, when it occurred. Results Of 665 children who underwent cardiac bypass surgery, 126 had a febrile episode postoperatively, 47 children with a proven bacterial infection and 79 without bacterial infection. Among the 68 children in whom fever developed within the first 5 postoperative days, procalcitonin level at fever day was significantly higher in those with bacterial infection (n = 16) than in those without infection (n = 52). Similarly, among the 58 children in whom fever developed after day 5 postoperation, a significant difference was found in procalcitonin level at fever day between those with (n = 31) and without (n = 27) bacterial infection. Conclusion During the critical early and late periods after cardiac surgery in children, procalcitonin level may help to differentiate patients with bacterial infection from patients in whom the fever is secondary to nonbacterial infectious causes.

We compared the clinical and bacteriologic response of 5-day treatment with cefixime, 8 mg/kg per day, with the response to trimethoprim-sulfamethoxazole (TMP-SMX), 10-50 mg/kg per day, the currently recommended therapy. Of the assessable children with acute, culture-proven shigellosis, 38 received cefixime and 39 received TMP-SMX. Pretreatment data on the two study groups were similar. In the first group, all isolates were susceptible to cefixime; in the TMP-SMX group, 32 isolates were resistant and 7 were susceptible to TMP-SMX. Clinical response (day 5) showed cure, improvement, and failure in 89%, 8%, and 3%, respectively, of the cefixime group, and in 25%, 44%, and 31%, respectively, of the TMP-SMX-resistant group (p0.001). Bacteriologic cure (day 3) occurred in 78% and 23% of the cefixime and TMP-SMX-resistant groups, respectively (p0.001). Clinical or bacteriologic relapse (day 12) was infrequent in both groups. The response to treatment of the cefixime and the TMP-SMX-susceptible groups was similar. No significant side effects were noted. We conclude that cefixime is superior to TMP-SMX in the treatment of suspected shigellosis in areas with a high rate of resistance to TMP-SMX.

The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 micrograms of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 micrograms of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis.

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.

Community-associated methicillin-resistant Staphylococcus aureus infections are increasingly being documented worldwide. In Israel, however, CA-MRSA infections have not yet been reported, so awareness among physicians may be low.To alert physicians to the possibility of CA-MRSA infection, which necessitates a distinct therapeutic approach.We present three children with soft tissue infections caused by CA-MRSA who were treated in our medical center from January to March 2009.In all three cases CA-MRSA was identified as the causative pathogen after surgical or spontaneous drainage. On susceptibility testing, the organisms were resistant to beta-lactam antibiotics but susceptible to clindamycin, rifampicin and trimethoprim-sulfamethoxazole.Physicians should maintain an index of suspicion for CA-MRSA infections. The antibiotic-resistance profile of S. aureus should be watched carefully, and in particular, cultures should be obtained whenever soft tissue infections fail to respond to conventional treatment.

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.To assess the rate of thrombocytosis (platelet count500 x 10(9)/L) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection.Clinical data on 469 infants agedor = 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between RSV-positive and RSV-negative infants.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.RSV-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.

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.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.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.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.