Genotype-Phenotype Correlations in Chronic Granulomatous Disease: Insights From a Large National Cohort.

Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic Granulomatous Disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the NADPH oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyper-inflammatory manifestations. We report a multi-center cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2,918 patients suffering from frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD, 56 of Jewish ancestry, 48 of Arabic ancestry and 6 non-Jewish/non-Arabic. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyper-inflammatory manifestations are described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39/110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multi-professional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management and prevention.

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy.

BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.

Skull Base Osteomyelitis in Children: Clinical Characteristics and Potential Implications.

OBJECTIVES: We describe 10 new cases of otogenic (n = 8) and nonotogenic (n = 2) skull base osteomyelitis (SBO) in previously healthy children and review the literature on SBO in the pediatric population. METHODS: We retrospectively analyzed the medical records of 10 children (age range 0.9-12.8 years) discharged with a diagnosis of SBO between 2015 and 2020 in 2 children's hospitals in central Israel. RESULTS: Five patients presented with fever and 5 with otological signs and symptoms. All 10 children underwent a comprehensive clinical evaluation, imaging studies (computerized tomography or magnetic resonance imaging) and laboratory investigations. The physical examination revealed neurologic findings, including nuchal rigidity, papilledema, and apathy, in 4 patients. All 8 otogenic patients underwent surgical intervention and the 2 nonotogenic patients, who were diagnosed as having deep neck and throat infections, responded well to treatment consisting of antibiotics without surgery. CONCLUSIONS: Early diagnosis of pediatric SBO can be challenging because the symptoms are often nonspecific. The final diagnosis relies mainly on imaging, preferably magnetic resonance imaging. Surgical intervention is usually mandatory in the otogenic patients, whereas the nonotogenic patients respond well to medical management alone.

Impact of COVID-19 Pandemic on Human Papillomavirus Vaccine Uptake in Israel.

OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.

Pediatrician, watch out for corona-phobia.

The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians' everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call "Corona-phobia". These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon.In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration. What is Known: • COVID-19 manifests as a mild disease in most children; however, children are an important reservoir and may become spreaders of the disease. • Social distancing and isolation are important tools in mitigating COVID-19 transmission. What is New: • This case series describes 7 cases with delayed diagnosis of every-day pediatric diseases that were not caused by COVID-19 but were highly influenced by different aspects of "Corona-phobia". • Our objective is to highlight the possibility that measures taken to mitigate this pandemic may lead to a substantial delay in the diagnosis of other non-COVID-19 related diseases.

Impact of rotavirus vaccine on admissions due to acute gastroenteritis and rotavirus gastroenteritis in Israel.

AIM: We examined the impact of insertion of the Rotavirus vaccine (RVV) into the Israeli National Immunisation Programme (NIP) on hospitalisations due to both acute gastroenteritis (AGE) and Rotavirus gastroenteritis (RVGE) in children. METHODS: We retrospectively analysed the medical records of children aged <5 years admitted with a diagnosis of AGE between 2008 and 2016 in two children's hospitals in central Israel. Clinical, laboratory, microbiological data and RV immunisation status were retrieved. Data were compared before and after the introduction of the RVV into the NIP. RESULTS: A total of 2042 children were admitted with AGE. Hospitalisations due to AGE and RVGE decreased from 3310 to 1950 and from 1027 to 585 per 100 000 admissions, respectively, after the RVV (relative risk reduction (RRR) of 41% and 43%, respectively). RV remained the most common pathogen in both study periods. There was no significant difference in the clinical course between immunised and non-immunised children admitted with RVGE. CONCLUSION: The introduction of the RVV to the NIP significantly reduced the admissions due to both AGE and RVGE in children <5 years. However, RV is still the most common agent for admissions due to AGE in this age group.

Benign course and clinical features of COVID-19 in hospitalised febrile infants up to 60 days old.

AIM: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities.

Retrospective study showed that bacterial gastroenteritis was an important cause of bloody stools in newborn infants.

AIM: Acute bacterial gastroenteritis is a major cause of morbidity and mortality, especially in the developing countries. We examined the incidence, clinical features and outcomes in the first week of life. METHODS: This was a retrospective study of culture-proven bacterial gastroenteritis in newborn infants that were diagnosed between January 2011 and September 2018 in a tertiary centre in Israel. RESULTS: There were 10 cases of culture-proven bacterial gastroenteritis, detected out of 91 stool cultures. All infants were born vaginally and nine were full-term infants. The annual incidence was 0.096 per 1000 live births. The responsible pathogen was Campylobacter in six patients, Salmonella in two and Shigella sonnei in two. The mean age of disease onset was two days of life. Antibiotics were given to five patients, but were inappropriate in two cases. Only one patient with the Shigella sonnei infection required respiratory support. All patients fully recovered. CONCLUSION: One in ten newborn infants with bloody stools had bacterial gastroenteritis, contradicting the low rates found in other studies and indicating the importance of considering this diagnosis. Antimicrobials active against Salmonella or Shigella should be given to newborn infants who have bloody stools and look ill.

Paediatric community-acquired bacteraemia, pneumococcal invasive disease and antibiotic resistance fell after the pneumococcal conjugate vaccine was introduced.

AIM: This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community-acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children. METHODS: Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18 years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced. RESULTS: There were 511 904 emergency department visits and 125 922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17 months) and 316 had CAB after the introduction (mean age 21 months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100 000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100 000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly. CONCLUSION: Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic-resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A).

PURPOSE: Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47phox deficiency. METHODS: Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47phox by immunoblotting and molecular confirmation by DNA sequence analysis. RESULTS: Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47phox deficiency. CONCLUSIONS: Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

Risk factors and epidemiology of pediatric ventriculoperitoneal shunt infection.

BACKGROUND: The aim of this study was to identify independent risk factors for cerebrospinal fluid shunt infection. METHODS: The medical records of all patients aged 0-18 years who underwent shunt-related surgery for the treatment of hydrocephalus at the present institution between January 1996 and December 2015 were reviewed. For each case, two randomly selected controls with no shunt infection, matched for year of surgery, were chosen. Demographic clinical and microbiological data were abstracted. RESULTS: A total of 1,570 shunt-related procedures met the inclusion criteria, yielding 68 infections (in 63 patients). The control group consisted of 132 infection-free patients. The average annual infection rate was 4.2% cases per year. The median time between shunt procedures to infection was 19 days (range, 1-2,181). On multivariate analysis, risk factors associated with increased risk for developing an infection included a history of two or more previous revisions (OR, 4.8; 95%CI: 1.5-15.9); and age <5 years (OR, 4.5; 95%CI 1.5-13.4). A neoplastic etiology for hydrocephalus was found to be a protective factor for shunt infection (P = 0.001). CONCLUSIONS: A history of shunt revision was the most significant risk factor in the development of subsequent shunt infection. Age >5 years was a protective factor. Future efforts should focus on modalities to optimize revision procedures and reduce the risk of subsequent infection.

Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients.

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.

Is There a Role for Placental Cultures in Cases of Clinical Chorioamnionitis Complicating Preterm Premature Rupture of Membranes?

Objective To assess the role of placental cultures in cases of preterm premature rupture of membranes (PPROM) complicated by chorioamnionitis and to determine the effect of positive cultures on short-term neonatal outcomes. Design A retrospective single-center study. The medical records of all women with PPROM between January 1, 2011, and December 31, 2015, were reviewed. Cases were divided into placental culture positive (group A) and placental culture negative (group B) groups. Maternal and pregnancy characteristics as well as short-term neonatal outcomes were compared between groups. Results During the 5-year study period, 61 cases of clinical chorioamnionitis complicating PPROM were diagnosed: 25 cases were culture positive (group A) and 36 were culture negative (group B). Neonatal outcome measures, including Apgar score at 5 minutes (p = 0.028; odds ratio [OR]: 5.27; confidence interval [CI]: 1.19-23.34), respiratory distress syndrome (p = 0.026; OR: 4.11; CI: 1.18-14.25), and neonatal infection (p < 0.0001; OR: 11.59; CI: 3.37-39.87) were significantly more common in group A newborns, regardless of gestational age at delivery as was the composite neonatal outcome (p = 0.017; OR: 7.35: CI: 1.42-37.79). Placental isolates were primarily Streptococci and Escherichia coli. Conclusion Placental cultures may be an essential predictor of neonatal morbidity in PPROM and may contribute to the modification of neonatal treatment.

Acute Mastoiditis Before Pneumococcal Vaccination: The Experience of a Large Tertiary Care Pediatric Hospital.

To report the experience of a large tertiary care pediatric center during a period of increasing Streptococcus pneumoniae antimicrobial resistance before the introduction of pneumococcal vaccine in Israel. Retrospective chart review of children diagnosed acute mastoiditis (AM) between January 1997 and December 2007. The children were divided into 4 age groups (6-11, 12-23, 24-35, and 36-40 months), and each group was compared with the others. A total of 198 AM episodes were recorded during the 10-year study period. The most prevalent pathogen was S. pneumonia, with a very low (15%) penicillin resistance rate (minimal inhibitory concentration ≥ 2). Complications were more prevalent in the 12- to 23-month age group. The number of AM cases increased during the study period. Penicillin resistance did not play an important role in determining the morbidity before the introduction of pneumococcal conjugate vaccine.

Immunisation led to a major reduction in paediatric patients hospitalised because of the varicella infection in Israel.

AIM: The varicella-zoster virus causes infections that are often mild but can cause substantial morbidity and mortality in otherwise healthy children. We examined trends in varicella-related hospitalisations before and after the implementation of a national two-dose varicella vaccination programme in Israel in September 2008. METHODS: This retrospective chart review, performed at three tertiary care paediatric hospitals in greater Tel Aviv, compared data from 2004 to 2008 and 2009 to 2012, before and after the varicella programme was launched. It included all children to the age of 18 who were hospitalised for conditions associated with the varicella infection. RESULTS: After the vaccination programme was introduced, the number of children hospitalised for varicella fell by 63% (p < 0.5), from 38.9 to 14.5 per 10 000, and there was a 75% reduction in children aged one to six. During the same period, the percentage of hospitalised children who were immunocompromised rose from 9.7% to 18.4% (p < 0.05). The most common complications were soft-tissue infections (60%), and the most prevalent pathogens were Group A ß-haemolytic streptococcus (53%) and Staphylococcus aureus (32%). CONCLUSION: The introduction of a two-dose immunisation programme dramatically decreased the varicella burden in Israel, leading to a major reduction in hospitalisation admissions linked to the infection.

Acute Childhood Encephalitis at 2 Tertiary Care Children's Hospitals in Israel: Etiology and Clinical Characteristics.

OBJECTIVES: The clinical characteristics, pathogens, and outcome were analyzed to investigate the etiology of acute pediatric encephalitis in 2 tertiary pediatric medical centers in Israel. METHODS: A retrospective study among children aged 1 month to 18 years hospitalized with the diagnosis of acute encephalitis between January 1999 and December 2009. Data on presenting symptoms, clinical findings, microbiological, virologic, electroencephalographic and neuroimaging studies, laboratory results, and hospital course were retrieved from the medical records and the computerized microbiology database. RESULTS: Forty-four children were included. An etiologic agent was identified in 11 (25%): Mycoplasma pneumoniae (n = 2), enterovirus (n = 3), herpes simplex virus (HSV) (n = 1), Epstein-Barr virus (n = 2), human herpes virus 6 (n = 1), influenza virus type A (n = 1), and varicella zoster virus (n = 1). Presenting features included fever (90% of patients), seizures (39%), focal neurological signs (18%), and decreased consciousness (67%). Diagnostic findings included pleocytosis in the cerebrospinal fluid (76% of patients), electroencephalographic abnormalities (78%), and neuroimaging abnormalities (34%). All patients were treated with acyclovir until negative result for HSV polymerase chain reaction was received from cerebrospinal fluid, the child with HSV encephalitis was treated with intravenous acyclovir for 3 weeks. The outcomes at the time of discharge were: normal (66%), motor difficulties (14%), global neurological deficits (7%), visual defects (2%), and hearing impairment (2%) and no deaths. CONCLUSIONS: The etiology of acute encephalitis remains unknown in the majority of cases. There was no correlation between adverse outcome and a specific etiologic agent. The high morbidity rate may suggest that current therapeutic modalities may not be sufficient.

Ecthyma gangrenosum skin lesions in previously healthy children.

UNLABELLED: Ecthyma gangrenosum (EG) is an uncommon skin lesion that usually develops in patients with known immune deficiency or who are on immunosuppressive treatment. We report on five previously healthy children presenting with EG. Three of them developed severe neutropaenia. Immunologic work-up revealed chronic neutropaenia in two. CONCLUSION: Recognition of EG is essential for providing early appropriate empiric antibiotic treatment. An immunologic work-up should be done, although a concomitant viral infection can be the predisposing factor.

Does extreme leukocytosis predict serious bacterial infections in infants in the post-pneumococcal vaccine era? The experience of a large, tertiary care pediatric hospital.

BACKGROUND: Extreme leukocytosis, defined as a peripheral white blood cell count greater than 25,000/mm, may alarm clinicians and prompt extensive evaluation in infants with fever, especially in the pediatric emergency department. METHODS: We reviewed data from children aged 3 to 36 months with extreme leukocytosis, fever and the risk of serious bacterial infections (SBI) at our institution from July 2010 to December 2012, a period after the universal introduction of pneumococcal vaccine. RESULTS: Serious bacterial infection was recorded in 57 (39%) of the 147 infants. The most common SBI were segmental or lobar pneumonia, in 28 (19%) patients, and urinary tract infection in 16 (10.9%) patients. Three patients had positive blood cultures, corresponding to a bacteremia rate of 2%. C-reactive protein was significantly higher in the SBI group than in the non-SBI group. CONCLUSIONS: All well-looking febrile infants with white blood cell greater than 25,000/mm should undergo a chest radiograph unless there are clear physical findings that indicate a different etiology. Urine culture should be considered in women. C-reactive protein can have an added value in the differential diagnosis.