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We assessed the humoral and cellular response to the fourth BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL. A total of 67 patients with CLL and 85 age matched controls tested for serologic response and pseudo-neutralization assay. We also tested the functional T-cell response by interferon gamma (IFNγ) to spike protein in 26 patients. Two weeks after the fourth vaccine antibody serologic response was evident in 37 (55.2%) patients with CLL, 20 /22 (91%) of treatment naïve, and 9/32 (28%) patients with ongoing therapy, compared with 100% serologic response in age matched controls. The antibody titer increased by 10-fold in patients with CLL, however, still 88-folds lower than age matched controls. Predictors of better chances of post fourth vaccination serologic response were previous positive serologies after second, third, and pre-fourth vaccination, neutralizing assay, and treatment naïve patients. T-cell response improved from 42.3% before the fourth vaccine to 84.6% 2 weeks afterwards. During the time period of 3 months after the fourth vaccination, 14 patients (21%) developed COVID-19 infection, all recovered uneventfully. Our data demonstrate that fourth SARS-CoV-2 vaccination improves serologic response in patients with CLL to a lesser extent than healthy controls and induces functional T-cell response.

Background Carbapenemase-producing enterobacteriaceae (CPE) can cause hospital outbreaks with considerable health and economic implications. Intensive infection control measures are implemented to identify CPE carriers and contain outbreaks. Methods We describe a CPE-NDM (New Delhi Metallo-beta-lactamase) hospital wide outbreak, in a tertiary care pediatric hospital, which evolved into a CPE-KPC (Klebsiella pneumoniae carbapenemase) outbreak before subsiding. Results At 10/20/21 rectal screening for CPE was performed in patients in the NICU (neonatal intensive care unit) because of known CPE carriers hospitalized there. Multiple CPE carriers were discovered, and a hospital-wide outbreak of CPE-NDM was identified. All patients who were potential contacts of CPE carriers throughout the hospital were isolated and screened twice a week, as part of intensive infection control measures. Between 10/20/21 and 12/07/21 46 patients carrying CPE-NDM were discovered. Continued screening between 12/15/21 and 04/18/22 identified 81 additional patients carrying CPE, however the carbapenemases identified in 78 of them were KPC. No known CPE-KPC carrier was hospitalized at the beginning of the KPC outbreak. Surprisingly, in 6 of the patients carrying CPE-NDM, repeat screening done months later found the carriage shifted from CPE-NDM to CPE-KPC. The results were validated and analyzed at the National Infection Control Laboratory. No significant morbidity or mortality was observed due to CPE carriage. CPE identification distribution by week and mechanism Conclusion We report an unusual sequence of two CPE outbreaks. We found no previous reports of consecutive outbreaks of CPE. Disclosures All Authors: No reported disclosures.

Background A host-protein score (BV) combining the circulating levels of TRAIL, IP-10 and CRP was developed for distinguishing bacterial from viral infection. BV’s potential to impact decision making at the emergency department (ED) was assessed by comparing BV to physician’s etiological suspicion. Methods Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. The main eligibility criteria were symptoms for less than 7 days and immunocompetence. ED physician’s initial etiological suspicion (bacterial/viral/I don’t know) and degree of confidence (low/medium/high) were recorded in a questionnaire. BV was interpreted based on pre-defined score thresholds (viral/bacterial/equivocal); the results were not available to the physician. The etiologic reference standard was based on the diagnoses (bacterial/viral/indeterminate) of 3 independent pediatricians who were provided with all available patient data but blinded to BV. BV’s potential to impact the physician’s etiologic accuracy was estimated according to alignment between BV and etiological suspicion as filled in the questionnaire (assuming full adoption of BV by the physician). Results Among 348 patients recruited, 290 met eligibility criteria and had requisite serum sample (Figure 1A). Median age was 1.3 years (interquartile range 1.7), 37.5% were female. 211 patients had questionnaires filled. BV matched physician’s label and reference standard in 72% of the cases (151/211; Figure 1B); of these, 52% (78/151) were labeled by the physician with low/medium confidence, i.e., BV could reinforce the physician’s suspicion. In 12% of the cases (26/211) BV aligned with the reference standard but not with the physician’s suspicion, and therefore could correct the physician's etiologic diagnosis. BV did not align with the reference standard in 7% of the cases (14/211) and was equivocal in 9% of the cases (20/211). Overall, BV could potentially correct physician diagnosis and reduce error >2-fold, from 16.1% to 8.1%. Figure 1.Assessing the potential impact of BV on ED physician’s etiologic accuracy. (A) Reference standard outcomes and BV scores. (B) BV versus adjudication-based reference standard and ED physician etiologic suspicion. Cases with missing questionnaire were omitted; n=211. Conclusion BV has potential to aid the diagnostic process. Future studies are warranted to assess the real-world impact of BV on ED practice. Disclosures Meital Paz, MD, MeMed: employee Oded Scheuerman, MD, MeMed: Grant/Research Support Ron Berant, MD, GE: Advisor/Consultant.

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.

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

Objective To describe the clinical features of osteoarticular infection in infants cared for in neonatal intensive care units (NICUs) and to assess the presence of multifocal infection. Study design Retrospective medical record review with structured data abstraction of infants with osteomyelitis or pyogenic arthritis or both in NICUs at 3 children's hospitals over a 29-year period. Results Of the 45 cases identified, 87% occurred in prematurely born infants, with a median gestational age of 27.4 weeks (IQR, 26, 31 weeks). Median postnatal age at diagnosis of infection was 33 days (IQR, 20, 50 days). Osteomyelitis was present without joint involvement in 53% and with joint involvement in 44% of cases. Methicillin-susceptible Staphylococcus aureus (71%) was the predominant pathogen, despite prevalent methicillin-resistant S aureus in community-associated infections. More than 1 bone was infected in 34% of cases. The femur (in 50% of patients) was the most frequently involved bone and the hip (in 20% of patients) was the most frequently involved joint. Bacteremia persisted for 4 or more days in 54% of patients with a positive blood culture despite active antimicrobial therapy. Conclusions Among infants with osteoarticular infection in NICUs, multifocal disease is common and frequently is unsuspected. Search for additional sites of infection including the hip is warranted following the diagnosis of osteoarticular infection at a single site. Involvement of contiguous joints should be suspected in cases of osteomyelitis; conversely the presence of pyogenic arthritis usually indicates extant osteomyelitis in a contiguous bone.

Background Acute invasive fungal rhinosinusitis has been associated with high mortality rates. Objective We aimed to explore the contribution of novel detection and treatment methods on the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis. Methods The records of all children with a hematologic or oncologic disease who developed acute invasive fungal rhinosinusitis between 2005–2020 were reviewed. Results Thirty-four patients were included. Aspergillosis and mucormycosis were diagnosed in 20 patients (59%) and 12 patients (35%), respectively. Panfungal polymerase chain reaction (PCR) was associated with a change of treatment in 36% of patients. A more aggressive surgical approach as well as treatment with liposomal amphotericin B and novel antifungals were adopted in recent years. Overall, 26% of patients died of disease, however no disease-specific death occurred since 2012. Diagnosis using panfungal PCR ( p = .04) and treatment with novel antifungal medications ( p = .017) were significantly associated with disease-specific survival. Conclusion Enhanced fungal detection using panfungal PCR and treatment with novel antifungal agents, combined with rapid diagnosis and treatment, aggressive surgical approach and better control over the underlying oncological disease, may significantly improve the outcome of immunosuppressed children with acute invasive fungal rhinosinusitis.

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.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.

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.

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.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.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.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.

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The aim of this study was to assess the contemporary management strategies and outcomes of disseminated mucormycosis in the pediatric population. Methods: We conducted a retrospective search in six large tertiary medical centers for all cases of disseminated mucormycosis that occurred between 2009–2020 in patients aged 1–20 years. Results: Twelve cases were identified. Underlying conditions included hematological malignancies (n = 10), solid tumor (post-autologous hematopoietic stem cell transplantations, n = 1), and solid organ (liver) transplantation (n = 1). In all cases, amphotericin B formulations were administered as first-line therapy, in eight cases, they were also administered in combination with an echinocandin or triazole. Seven patients underwent surgical debridement procedures. The six-week mortality was 58%. Among the patients diagnosed between 2009–2015, one of the six survived, and of those diagnosed between 2016–2020, four of the six were salvaged. Conclusions: Disseminated mucormycosis is a life-threatening and often fatal disease, and improved diagnostic and therapeutic strategies are needed. Nevertheless, in this population-based study, five patients (42%) were salvaged through combined liposomal amphotericin/triazole treatment and extensive surgical interventions.

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

BACKGROUND Q fever is a zoonosis caused by the bacterium Coxiella burnetii (C. burnetii) with a worldwide distribution. Our aim was to assess the epidemiology, clinical manifestations and treatment regimens of chronic Q fever infections in Israeli children during the past 25 years. METHODS Cases were collected from the national Q fever reference laboratory database. Demographic, epidemiologic and clinical data were reviewed using a structured questionnaire sent to the referring physician. Cases were defined according to the new Dutch Consensus Guidelines. RESULTS A total of 16 children originating from all regions of the country were found positive for chronic Q fever infections. The most common infection site was bone or joint (8/16, 50%), all in previously healthy children. Endovascular infections were found in 5 children (31%), all with an antecedent cardiac graft insertion. According to the new Consensus Guidelines, 9 children (56%) had a proven infection, 3 (19%) a probable infection and 4 (25%) a possible chronic Q fever infection. Almost all cases were treated with a long-term antibiotic regimen, often necessitating a change in medication because of persistent or rising titers. CONCLUSIONS Although pediatric chronic Q fever infections are rare, incidence has been rising. The most common infection site was bone or joint. A high index of suspicion is necessary, even in cases of previously healthy children without a possible exposure history. Use of the relatively new diagnostic tools in combination with serologic methods is helpful in diagnosing proven cases. There is no consensus as to the selection or duration of antibiotic treatment.

AIM This study investigated the under-researched area of annual influenza vaccination rates in children with chronic kidney disease and identified reasons for nonimmunisation. METHODS A prospective cross-sectional study was conducted in the nephrology clinic and dialysis unit of a tertiary paediatric medical centre from August to October 2011 and September to October 2012. Parents were asked to complete a questionnaire on their child's immunisation against influenza. RESULTS Of the 217 children studied, 45.6% were vaccinated against influenza. The major reason for nonimmunisation was because the parents had not received the necessary information from the primary physician or treating nephrologist. The nonvaccinated children were significantly more likely to be less than two years old and female and to have parents who did not believe in the benefits of vaccination (p < 0.05). Of the parents who did not vaccinate their child, 38% claimed they would have done so if the vaccine had been offered in the nephrology clinic. CONCLUSION Children with kidney disease had a higher annual influenza vaccination rate than the general population, but it was still suboptimal. Nephrologists should be alerted to the need to provide parents with information on influenza vaccinations and they should be available in nephrology clinics.

Neonatal serum detection of cytomegalovirus (CMV) immunoglobulin M (IgM) has low sensitivity in identifying congenital cytomegalovirus (cCMV). Several reports have endeavored to associate the presence/absence of IgM to disease severity. Data were collected for all infants with cCMV followed in our clinic. Infant outcome after birth was compared between infants who tested positive or negative. Sensitivity of positive IgM in diagnosing cCMV was 40.7%. The rate of symptomatic disease in those who tested positive was statistically higher (67.7%, P < .001). Odds ratio for symptomatic disease in infants with positive IgM born after a maternal primary infection was 3.47 (95% confidence interval = 1.7-7.1). Positive IgM was found in only 48.8% of symptomatic and 22.1% of asymptomatic children. Our results demonstrated a low sensitivity of IgM in diagnosing cCMV. However, while a positive IgM antibody for CMV is associated with a more symptomatic disease, it does not serve as a precise laboratory marker for a severity.

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.

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.

Objectives Arterial catheters may serve as an additional source for blood cultures in children when peripheral venipuncture is challenging. The aim of the study was to evaluate the accuracy of cultures obtained through indwelling arterial catheters for the diagnosis of bloodstream infections in critically ill pediatric patients. Design Observational and comparative. Setting General and cardiac ICUs of a tertiary, university-affiliated pediatric medical center. Patients The study group consisted of 138 patients admitted to the general or cardiac PICU in 2014-2015 who met the following criteria: presence of an indwelling arterial catheter and indication for blood culture. Interventions Blood was drawn by peripheral venipuncture and through the arterial catheter for each patient and sent for culture (total 276 culture pairs). Measurements and main results Two specialists blinded to the blood source evaluated each positive culture to determine if the result represented true bloodstream infection or contamination. The sensitivity, specificity, and positive and negative predictive values of the arterial catheter and peripheral cultures for the diagnosis of bloodstream infection were calculated. Of the 56 positive cultures, 41 (15% of total samples) were considered diagnostic of true bloodstream infection. In the other 15 (5%), the results were attributed to contamination. The rate of false-positive results was higher for arterial catheter than for peripheral venipuncture cultures (4% vs 1.5%) but did not lead to prolonged unnecessary antibiotic treatment. On statistical analysis, arterial catheter blood cultures had high sensitivity (85%) and specificity (95%) for the diagnosis of true bloodstream infection, with comparable performance to peripheral blood cultures. Conclusion Cultures of arterial catheter-drawn blood are reliable for the detection of bloodstream infection in PICUs.

Aim This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection. Methods We included all infants with cCMV infection who were followed in our clinic for more than a year with only LSV signs of brain involvement on initial brain ultrasound. Group one comprised 13 infants with no hearing impairment at birth who were not treated with gan/valganciclovir during 2006–2009. Group two was 51 infants with LSV and no hearing impairment who had been treated since mid-2009. Group three was 25 infants born with LSV and hearing loss, who had been treated from birth. Group four was 52 control infants born during the same period with asymptomatic cCMV. Hearing tests were performed during the neonatal period and every four to six months until four years of age. Results Hearing deterioration was more extensive in group one (85%) than in group two (0%, p

Objectives Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients. Methods The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate. Results The study population included 273 patients (50% female), with a median age of 10 years (range, 2–18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents’ information and knowledge of, as well as their personal beliefs regarding the vaccine ( P Conclusions Influenza vaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine.

Hepatitis B virus (HBV) vaccination has decreased the prevalence of chronic HBV infections and their sequelae. However, whether vaccination at birth provides lifelong protection is unclear.To assess long-term immunity following neonatal HBV immunization in a large population-based cohort.Using the database of a 2 million member sick fund in Israel, we identified all subjects born after introduction of universal HBV vaccination in Israel (January 1992 through December 2014), that were tested for hepatitis B surface antibody (anti-HBs Ab's). Years since vaccination were categorized into 5-year groups and linear trends in the seroprevalence of HBV immunity were calculated. Anamnestic response and presence of Hepatitis B surface antigen (HBs Ag) were assessed.Included were 20,634 tested individuals. Mean (±SD) age at testing was 14.8 (±5.4) years. Mean anti-HBs Ab levels declined with time to 16.39 mIU/ml in the 15-20 year group (P 0.001). The proportion of negative results increased gradually (P 0.001) to 66.7% after 15 years. Anamnestic response assessment showed that 604 of 644 seronegative subjects (93.8%, 95% CI: 91.6-95.5%) became seropositive after a booster dose. HBs Ag was identified in 91 of the 20,634 (4.4 per 1000 study participants).Following vaccination, anti-HB's Ab's progressively decline, with only a third of the population retaining protective levels after 15 years. In adolescence, anamnestic response shows that nearly all revaccinated adolescents exhibit immunity. A low rate of Hepatitis B infection was demonstrated despite vaccination of nearly all newborns.

Introduction Acute appendicitis is the most common emergency condition in pediatric surgery. Historically, a triple-antibiotic therapy consisted of ampicillin, gentamicin, and clindamycin has been used postoperatively for perforated appendicitis. According to recently published trials, dual therapy consists of ceftriaxone and metronidazole only, offers a more efficient and cost-effective antibiotic management compared with triple therapy. Based on these results, our department applied dual antibiotic therapy for children with perforated appendicitis that underwent appendectomy from 2009 and forth. Aim The aim of our study was to compare postoperative outcomes between patients treated with triple therapy (ampicillin, gentamicin, and metronidazole) (group A) versus dual therapy (ceftriaxone and metronidazole) (group B). Methods Clinical and laboratory data were retrospectively collected by review of the medical records for all children who underwent appendectomy for the perforated appendix at the Schneider Children's Medical Center of Israel, a tertiary pediatric care center between 2007 and 2011. Children with perforated appendicitis received antibiotic therapy in accordance with the hospital's guidelines that were valid at the time the surgery took place. In the first period (years 2007–2009) (group A) a triad of ampicillin, gentamicin, and metronidazole and the second period (2009–2011) (group B) dual therapy consists of ceftriaxone and metronidazole. The two groups were compared for outcome and complications, such as wound infections, changing of antibiotic therapy, and length of stay. Results During the study period 1,203 patients underwent an appendectomy. Of these, 175 patients were diagnosed with perforated appendix and were treated with postoperative antibiotic's regimen. Group A and group B consisted of 89 and 86 patients, respectively. The two groups were not different significantly in terms of demographic data, length of stay, or readmission rates. However, more rates of wound infection and changing of antibiotic therapy were seen in group B, although not statistically significant (p = 0.064). Conclusion Dual antibiotic therapy for perforated appendicitis is a cost-effective and efficient mode of therapy compared with triple-antibiotic's regimen. However, prospective studies are required to determine whether this policy is associated with higher rates of wound infections and change in antibiotic therapy.

Introduction Surgical antibiotic prophylaxis (AP) guidelines balance the need to prevent infection with the risks of adverse drug effects. Our aim was to assess compliance with AP guidelines. Methods A retrospective study was performed in a pediatric medical center. Included were patients aged 0 to 18 years that underwent clean-contaminated surgery during a 1-year period (2008–2009) and required AP. Compliance with four AP bundle guidelines was evaluated. Risk factors for noncompliance were identified using univariate and multivariate analyses. Results AP was given to 239 of 247 (96.8%) of patients. Complete compliance with AP guidelines was achieved in 16 of 247 (6.5%) patients. Compliance with guidelines for appropriate antibiotic, drug dose, correct timing, and treatment duration were found in 97.1, 52.2, 31.9, and 35.9% of patients, respectively. Multivariable analysis showed that inappropriate timing was associated with age ≥ 4 years ( p = 0.002), urgent surgery ( p = 0.0018), surgical department AP administration ( p = 0.0001), and night-time surgery ( p = 0.015). Incorrect AP dose was associated with presence of comorbidities ( p = 0.006). No risk factor was related to incorrect AP duration. Conclusions We have found a low rate of full compliance with AP guidelines. AP should only be given in the operating room. Increased awareness to AP guidelines is needed.

Aim Viral pneumonia is a serious complication in immunocompromised children. Its aetiology is difficult to identify owing to the limitations of conventional microbiological tests. The aim of this study was to determine whether polymerase chain reaction (PCR) assays for respiratory viruses increase the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised children. Methods BAL samples obtained from immunocompromised children hospitalized with pneumonia were processed for respiratory viruses by viral culture, rapid antigen test and PCR (for CMV, adenovirus, influenza, parainfluenza, herpesvirus, RSV and hMPV). Results The study group included 42 patients (mean age 7.2 ± 5.1 years) with 50 episodes of clinical pneumonia (50 BAL samples). Forty viral pathogens were identified in 30 episodes (60%). PCR increased the diagnostic rate by fourfold (75% identified by PCR alone, p

PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ≥80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.

Antifungal prophylaxis is increasingly used in very low birth weight (VLBW) infants who are at risk for severe fungal infections. Our objective was to assess the effectiveness of targeted fluconazole prophylaxis for high-risk VLBW infants. A retrospective cohort study with historical controls was performed. During the period 2007-2008, all high-risk VLBW infants (birth weight, ≤1,000 g; gestational age, ≤28 weeks; seven antimicrobial therapy or additional risk factors present) received fluconazole prophylaxis until risk factors were not present. Treated infants were compared to a gestational age- and birth weight-matched untreated cohort. Statistical analyses used univariate and multivariate analyses. The main outcome variable was a breakthrough fungal bloodstream infection (BSI). The prophylaxis cohort of 130 VLBW infants was compared to 319 control infants. The rate of fungal infections was significantly lower in the fluconazole prophylaxis group (1 of 130 vs. 19 of 319, p = 0.016); however, they did not differ in mortality (16.2 vs. 15 %, p = 0.77) or complications of prematurity. Fluconazole prophylaxis was associated with a significant decrease in candidal BSI (odds ratio, 0.05; 95 % confidence interval, 0.005-0.523). Selective vs. nonselective prophylaxis reduced the number of infants treated from 247 to 130. Conclusion Targeted fluconazole prophylaxis in VLBW infants is effective in preventing fungal infections without increasing the risk of BSI among low-risk infants.

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 (

Background In previous studies, lenticulostriated vasculopathy (LSV) was detected in 0.4–5.8% of neonates who had undergone brain ultrasound studies during the neonatal period. Most infants were referred from neonatal intensive care units. Various clinical conditions were associated with LSV including intrauterine infections. Objective To investigate whether LSV as a single abnormal finding in neonates with congenital cytomegalovirus (CMV) infection is a sign of central nervous system (CNS) involvement. Methods Ultrasonographic and clinical data of all infants with congenital CMV infection, followed in our hospital, were collected. All infants with symptomatic congenital CMV infection and CNS involvement were treated with ganciclovir for 6 weeks, followed by valganciclovir until the age of 1 year. Infants with asymptomatic as well as symptomatic infections were followed up with brainstem evoked response and behavioural studies every 4 months until 4 years of age. Results 92 infants diagnosed with congenital CMV infection were included in the study. In 50 (54.3%) infants, LSV was detected on initial brain ultrasound. Among these patients, 21 (42%) infants had other ultrasonographic findings consistent with congenital CMV infection; 11 (22%) had other symptoms of CNS involvement and in 18 (36%) cases the only abnormal finding was LSV. In 9 of the 18 infants with LSV as the only finding on initial examination, antiviral therapy was not started. Hearing deterioration developed in all nine infants between ages 4 and 34 months. Subsequent to these cases, the authors modified their therapy protocol and began treating congenital CMV infants with only LSV. 9 infants were treated and all maintained normal hearing after 8–27 months of follow-up (p Conclusions LSV is a common finding in infants with symptomatic congenital CMV infection and is a sign of CNS involvement. Moreover, LSV is a possible marker of high risk for sensorineural hearing loss in infants with congenital CMV infection.

Background Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population. Procedure The medical records of all children with malignancies diagnosed with an invasive fungal infection in 1998–2006 at a tertiary pediatric medical center were reviewed for demographic, clinical, and laboratory data. Invasive fungal infection was diagnosed according to the latest EORTC/MSG criteria. Results Of the 1,047 children hospitalized in the hematology/oncology department during the study period, 75 (7.2%) were diagnosed with a proven (n = 16, 21.3%), probable (n = 18, 24%), or possible (n = 41, 54.7%) invasive fungal infection. Fifteen (20%) had candidemia (non-albicans in 60%), and 60 (80%) had a mold infection (non-Aspergillus in 55%). Crude mortality was 21.7%. The most common underlying diseases were myeloid leukemia (n = 26, 34.7%) and acute lymphoblastic leukemia (n = 24, 32%). Compared to other malignancies, acute myeloid leukemia was significantly associated with the development of invasive fungal infections. Profound neutropenia and high treatment intensity were present in 89% and 73% of patients with IFI respectively. Conclusions The current mortality rates of invasive fungal infection in children with cancer are lower than previously reported in children and adults. However, the proportion of non-albicans candidemia is increasing, and non-Aspergillus molds are emerging as important pathogens, which may have important implications for prophylaxis and empiric therapy. Improved prevention, early detection, and advanced treatment strategies are needed to improve the outcome. Pediatr Blood Cancer 2011;56:1092–1097. © 2011 Wiley-Liss, Inc.

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.

Mucormycosis has emerged as an increasingly important infection in patients with hematological malignancies, and is associated with considerable morbidity and mortality. However, contemporary data concerning epidemiology and outcome in children is lacking. Here we report a nationwide multicenter study of mucormycosis among children with hematological malignancies. Between the years 2004-2017, 1136 Israeli children aged ≤18 years with acute leukemias (acute lymphoblastic leukemia (ALL)-941; acute myeloid leukemia (AML)-195) were prospectively enrolled on a centralized clinical registry. Fungal infections, including mucormycosis, were prospectively and retrospectively captured. In addition, all 7 pediatric hematology centers were required to search hospital medical records, microbiology databases, and pathology information systems for cases of mucormycosis. Following central revision, 39 cases of mucormycosis were identified. Patient characteristics: Median age at mucor diagnosis: 13.5 years. Underlying diseases: ALL-27, AML-9, other-3. In 24 patients mucormycosis occurred during frontline therapy of their disease, and in 15 patients at relapse. Known risk factors included stem cell transplantation (SCT)-13 (33%), severe neutropenia-33 (85%) and corticosteroids-26 (67%). Among 20 patients on frontline ALL therapy, mucormycosis was diagnosed during induction in 13 cases, reinduction-6 cases, consolidation-1 case. Twenty-five patients with mucormycosis were enrolled on the national acute leukemia registry (not included: other malignancies, non-Israeli patients, relapsed leukemia with primary diagnosis preceding registry initiation, secondary AML). An analysis of registry cases demonstrated that the incidence of mucormycosis did not significantly increase during the study period. There was no seasonal clustering. Mucormycosis was significantly more common among patients ≥10 years old (4% vs 1%, p=0.004). Among patients on frontline treatment, mucormycosis was significantly more common in high-risk (HR) ALL patients (6%) than in non-HR (1%) or AML (1%) patients (p=0.001). Mucormycosis: Patterns of infection included sinusitis/sino-orbital-16 (41%), rhinocerebral-8 (21%), pulmonary-3 (8%), mandibular -4 (10%), gastrointestinal-1, cutaneous-1, otomastoiditis-1, disseminated-6 (15%). The majority (46%) were caused by Rhizopus spp. EORTC criteria: proven-30, probable-7, possible-2 (pathognomonic radiological findings and molecular diagnosis). Treatment: Nineteen patients were treated with amphotericin B formulations only and 19 received combined antifungal treatment. Nine patients received step-down treatment with posaconazole/ isavuconazole. In addition, 33 patients underwent surgical interventions, 26 underwent 2 procedures or more (range 2-14). Median time from presentation to antifungal treatment-3 days. Outcome: Twenty-one patients died, 15 of mucormycosis, 3 of other toxicities, 3 of leukemia. Factors significantly associated with mortality from mucormycosis were preceding SCT (p=0.01), less than 2 surgical interventions (p=0.0003) and relapsed disease (p=0.006). Eight-year OS of the whole cohort, those on frontline therapy and relapsed patients was 42% (±21%), 70%(±13%), 13%(±66%), respectively. Eight-year cumulative incidence of death from mucormycosis (CIDM) in those subgroups was 40%(±8), 21%(±8), 67% (±13), respectively. To our knowledge, this is the largest population-based study of mucormycosis in children with hematological malignancies. Our study demonstrates that mucormycosis is an age-dependent toxicity, significantly more common in patients ≥10 years of age. A striking finding was the high incidence of mucormycosis among patients on frontline high-risk ALL therapy, a fact which may reflect the increasing intensity of childhood ALL treatment. In a cohort of 24 patients who developed mucormycosis on frontline therapy, including 2 patients with AML and 13 with HR-ALL, 8y-OS was 70% and 8y-CIDM was 21%.The majority of patients in this cohort were salvageable through control of underlying disease, rapid instigation of antifungal treatment, and surgical debridement procedures, albeit in some cases at a price of mutilation and long-term sequelae. Future research should focus on the complex interactions between fungi and host, and on developing novel therapeutic strategies. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Background Osteomyelitis and septic arthritis are important infections in neonates in intensive care units. The literature on neonatal osteoarticular infections during the past twenty years, a period during which there was an emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), is limited. The purpose of this study was to describe a case series of neonatal osteoarticular infections during recent decades. In particular, we sought to describe the current microbiology, prevalence of multi-bone and contiguous joint involvement, and proportion of cases with pyogenic arthritis of the hip. Methods Multi-center retrospective chart review. Cases were identified through NICU registries at 2 tertiary/quaternary children hospitals between 1993 and 2017. The diagnosis required suggestive clinical findings plus radiological findings or positive blood, joint fluid, or bone culture. Results Thirty cases were identified. The median gestational age was 28 weeks, with 24 (80%) cases occurring in premature babies. The median age at time of diagnosis was 33.5 days (range, 11–175) days. The most common localized clinical findings were erythema (66%) and swelling (60%); the most common systemic finding was apnea (53%). Seventy percent had osteomyelitis, 27% had both bone and joint involvement, and one had septic arthritis only. Eight babies (27%) had an infection in more than one noncontiguous site. The most commonly identified bone was the femur (41%) and joint was the knee (20%) followed by hip (17%). Of the 5 babies with hip infection, two were recognized more than 48 hours after initial presentation. An ultrasound of the hip was performed on 12 babies (40%), including 4 out of the 5 who had surgical drainage of the hip. Cultures of blood, joint fluid, and bone were positive in 23, 6, and 2 babies, respectively. Methicillin-susceptible S. aureus (71%) was the most common pathogen followed by MRSA (21%). Conclusion Neonates in a NICU with osteoarticular infection frequently have multiple sites of involvement. The hip joint is infected in a sizeable minority of babies with osteoarticular infection. In view of the importance of early diagnosis and surgical drainage of pyogenic hip arthritis, ultrasound of the hips should be considered in neonates in a NICU with osteoarticular infection at any body site. Disclosures All authors: No reported disclosures.

Aim: To further characterize apnoea(s) complicating bronchiolitis because of respiratory syncytial virus (RSV), to describe the incidence of this complication and identify possible risk factors for apnoea(s) and its development. Methods: The files of infants admitted to the paediatric intensive care unit (PICU) for RSV bronchiolitis during three bronchiolitis seasons (2004–2007) were reviewed for demographic, clinical and laboratory parameters. Parameters were compared between patients with and without apnoeas. Results: Seventy-nine patients met the study criteria: 43 were admitted to the PICU for central apnoeas and the remainder for respiratory distress or failure. The percentage of infants admitted for apnoea increased during the study period (28.6 to 77.1%, p = 0.004). The overall prevalence of apnoea in this population was 4.3%. Possible risk factors for apnoea(s) were younger age (1.3 vs. 4.3 months, p = 0.002), lower admission weight (3.3 vs. 5 kg, p

Peripherally inserted central venous catheters (PICCs) are frequently used in infants and children. However, only limited data are available on current infectious and noninfectious complications of PICCs in this patient population. The aim of the study is to define the current rate of infectious and noninfectious complications of PICCs, the causative agents, and to define possible risk factors associated with these complications.A prospective surveillance study was conducted at the Schneider Children Medical Center of Israel. All patients in whom a PICC was inserted between August 2004 and October 2006 were included. Demographic, clinical, and microbiologic data were collected by a questionnaire completed by the anesthesiologist at the time of insertion and removal of each catheter. Items covered epidemiologic, clinical, and microbiologic data.A total of 279 PICCs were inserted in 221 patients. There were no complications at insertion. Mean dwell time was 30 days. One hundred seventy-seven (63%) of all PICC placements were free of complications. Twenty-six catheters (9.3%) were dislodged accidentally; 38 (13.6%) were removed for mechanical problems: tears in 5, leaks in 12, and obstructions in 21; 38 (13.6%) were removed for an infectious complication: phlebitis in 13 (4.6%, 1.5/1000 PICC days), exit-site infection in 10 (3.5%, 1.1/1000 PICC days), PICC-associated bloodstream infection in 12 (4.3%, 1.4/1000 PICC days), and PICC-related bloodstream infection in 4 (1.4%, 0.4/1000 PICC days); 15 more were removed for presumed infection (5.3%, 1.7/1000 PICC days). On multivariate analysis, composite indication for PICC use and older patient age were significantly associated with infectious complications.PICCs are safe and may be used for prolonged periods. In our center, the rates of infectious complications are lower than for tunneled central venous catheters. Accidental dislodgement is not uncommon and may be prevented by use of sutures, occlusive dressing, and education of patients, families, and medical staff.

To determine the antibiotic susceptibility of Helicobacter pylori isolates from Israeli children; assess the role of previous antibiotic use in the development of antibiotic resistance and examine the possibility of simultaneous colonization of strains with different resistance patterns in the same patients.A prospective case-series design was used. The study group included 174 patients aged 1-18 years referred to the Schneider Children's Medical Center of Israel for gastroscopy over a 2.5-year period. Antibiotic susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin was determined by E-test on gastric biopsies (2 per patient). Clinical and demographic data were obtained by questionnaire.Cultures for H. pylori yielded 55 isolates from 53 children. In treatment-naïve children, the prevalence rate of primary resistance to clarithromycin was 25% and to metronidazole, 19%. Respective rates in children previously treated for H. pylori infection were 42% (p = 0.22) and 52% (p = 0.016). Simultaneous resistance to both drugs was found in 13% of isolates (n = 7), all from children with previous treatment failure. No resistance was found to amoxicillin, tetracycline or levofloxacin. Clarithromycin resistance was associated with macrolide use for any indication during the previous year (p = 0.033). In 2 patients (3.8%), a different H. pylori strain was cultured from each biopsy.H. pylori resistance to clarithromycin and metronidazole is high in Israeli children, particularly in those previously treated for H. pylori infection, in whom culture-based treatment should be considered. The simultaneous colonization of multiple strains in a minority of patients needs to be further characterized.

The purpose of this study was to assess the long-term effectiveness of the antibiotic lock technique (ALT) in conjunction with systemic antibiotics for the salvage of long-term central venous catheter (CVC)-associated coagulase-negative Staphylococcus (CONS) bloodstream infections (BSIs) in children. A retrospective study of children with CVC-associated CONS BSIs treated with systemic vancomycin and ALT with vancomycin was carried out. The primary outcome was the immediate and 3-month success rate of salvage of the CVC. During the study period, 23 patients had persistent CONS bacteremia and were treated with ALT and systemic vancomycin. Of the 23 vancomycin lock treatments, eight catheters were removed during the acute event because of persistent bacteremia, six had relapse of CONS bacteremia within 30 days, and two had relapse within 90 days. Only seven CVCs (30%) were salvaged. Long-term transcutaneous CVCs (Hickman CVCs) were significantly associated with higher salvage rates than implantable ports (75% vs. 18%, P = 0.05). ALT with vancomycin for CVC-associated bacteremia has a limited long-term effectiveness, especially with implantable ports. Larger prospective studies are needed for the long-term evaluation of this technique.

The yearly seasons are marked by changes in the amount of sunlight. Ultraviolet radiation (UVR) is known to adversely affect the course of viral infections, immunologic memory and cellular and humoral immune responses. Our objectives were to investigate potential differences in the immune response of the rubella vaccine after 3-4 years by season of inoculation. Children aged 4-5 years attending four kindergartens in villages in northern Israel, all of whom had been vaccinated at 1 year of age, were enrolled in the study. Participants were divided into three groups by season of the year in which the inoculation was performed: summer (N = 63), winter (N = 36) and intermediate (N = 104). Main outcome measures were mean geometrical titer of rubella antibodies and complete, partial or no immunity to rubella by season of inoculation. Of the 203 children tested, 186 (91.6%) had adequate antibody levels, 7 (3.4%) had equivocal levels and 10 (4.9%) had inadequate levels. Significantly higher mean geometrical titers were found in the winter-inoculated compared with the summer-inoculated group (73.0 ± 2.6 vs 47.6 ± 2.8; p < 0.05). The same tendency was noted in the percent of infants properly immunized. This preliminary study shows a strong correlation between the immune response to rubella vaccine and the season of vaccination. Immunogenicity may be improved by inoculating children during seasons of less sunlight or by reducing the children's exposure to sunlight following inoculation. This practice is especially important in areas with extreme seasonal variability in solar radiation and tropical areas. Further studies are needed to corroborate and expand these findings.

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.

Urinary tract infection (UTI) differs between preterm and older infants and children in terms of prevalence, clinical presentation, causative organism, and rate of underlying renal anomalies. Data on risk factors of UTI in preterm infants are limited. The aim of this study was to characterize UTI both clinically and microbiologically in premature infants and to define possible risk factors and the role of breastfeeding in its development. This case–control study was conducted in a tertiary-care neonatal intensive care unit (NICU) between 1995 and 2003. The study group included all premature infants (

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.