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This study analyzes prospectively the antibiotic prescription habits in terms of appropriateness of use and cost pattern effects in the paediatric wards of two different university hospital patient set-ups. Data on demographics, discharge diagnosis, antibiotic utilization and costs were collected prospectively from the children's individual electronic charts at Rambam Health Care Campus (R) and Kaplan Medical Centre (K) in Israel. A total of 505 and 497 children from R and K units, respectively, were screened. Of the surveyed population, 239 and 330 children in the R and K units were hospitalized due to infectious diseases. The antibiotic appropriateness for the R and K units were 84% and 91%, respectively (p>0.5). Total antibiotics Defined Daily Dose (DDD) and Drug Utilization 90% (DU90%) index were 241.7 and 217.5 for the R unit and 388 and 349.2 for the K unit, (p

Aims: Brain abscess is rare in children. Predisposing factors are found in almost 85% of cases. Overall, 25% of brain abscesses develop in children, mostly in the 4–7 years age group. Our study aimed to characterize children with brain abscesses treated in our hospital, identify risk factors, pathogens and short-term outcome. Methods: A retrospective cohort of 20 years period, (1989–2009) included 27children (0–18 years). Medical records were analysed for age, gender, presenting symptoms and signs, predisposing factors, laboratory tests, imaging, microbiology results, treatment and outcome. Results: Of all the children, 63% (17/27) were male patients; mean age was 7.9 years and 52% were referred from other hospitals. Predisposing factors were identified in 81%, congenital heart disease and otitis were rare and sinusitis was found in 22% of the children. Main symptoms and signs included headaches, fever, neurological signs convulsions, (41%, 81%, 78% and 41% respectively). In 30% of cases, cultures were sterile. All patients were operated in addition to antibiotic treatment. Outcome was good with low mortality rate (3.7%). Conclusions: Manifestations of brain abscess may be subtle. A high index of suspicion and early imaging are warranted, different predisposing factors may reflect early intervention for congenital heart diseases. Mortality is rare in the modern medicine era.

Background.Carbapenem resistance among isolates of Klebsiella pneumoniae has been unusual.Objectives.To identify risk factors for infection with carbapenem-resistant K. pneumoniae (CRKP) and to characterize microbiological aspects of isolates associated with these infections.Design.Retrospective case-control study.Setting.A 900-bed tertiary care hospital.Results.From January 2006 through April 2007, K. pneumoniae was isolated from 461 inpatients; 88 had CRKP infection (case patients), whereas 373 had carbapenem-susceptible K. pneumoniae infection (control subjects). The independent risk factors for infection with CRKP were prior fluoroquinolone use (odds ratio [OR], 1.87 [95% confidence interval {CI}, 1.07–3.26]; P = .026), previous receipt of a carbapenem drug (OR, 1.83 [95% CI, 1.02–3.27]; P = .042), admission to the intensive care unit (OR, 4.27 [95% CI, 2.49–7.31]; P < .001), and exposure to at least 1 antibiotic drug before isolation of K. pneumoniae (OR, 3.93 [95% CI, 1.15–13.47]; P = .029). All CRKP isolates carried the blaKPC gene. Approximately 90% of the tested isolates carried the blaKPC-2 allele, suggesting patient-to-patient transmission. Almost all CRKP isolates were resistant to all antibiotics, except to Colistin (resistance rate, 4.5%), gentamicin (resistance rate, 7%), and tigecycline (resistance rate, 15%).Conclusions.CRKP should be regarded as an emerging clinical threat. Because these isolates are resistant to virtually all commonly used antibiotics, control of their spread is crucial.

Background A pediatric septic hip is a serious condition that must be recognized and treated as early as possible. We describe the clinical course of children with septic hip that were treated with aspiration of the hip joint in the emergency department (AHED). Methods This was a retrospective case series analysis. Results Between January 1, 2007, and December 31, 2014, 17 children with septic hip were diagnosed by emergency physicians using point-of-care ultrasonography. All were treated with AHED. During hospital admission, a median of 2 (interquartile range [IQR], 2-3) follow-up sonographic examinations per patient was performed; 10 (59%) patients did not have another hip aspiration, and 7 (41%) had a median of 1 (IQR, 1-3) hip joint aspiration under sedation. Median length of antibiotic treatment was 28 days (IQR, 21-40). No patient underwent arthrotomy, and all recovered without disability in up to 4 years of follow-up. Conclusions The results of this cohort suggest that AHED with repeated aspirations as needed is an effective treatment for children with septic hip.

Human herpes virus-6 (HHV-6) reactivation after hematopoietic stem cell transplantation (HSCT) is well known and has been linked with several clinical manifestations. The significance of HHV-6 viremia and related complications in this setting is still unclear.To estimate the incidence of HHV-6 reactivation and associated morbidity in children undergoing allogeneic HSCT.Blood samples obtained weekly (for cytomegalovirus surveillance) from children who underwent allogeneic HCST during the period January 2006-June 2010 were retrospectively tested for the presence of HHV-6 DNA using standard real-time polymerase chain reaction (PCR) assay. Clinical records were reviewed for correlation between viremia and clinical manifestations.Samples from 39 children were tested. Twenty patients had viral loads above 1000 copies/ml (51%) in at least one sample. Higher viral loads were seen in patients with primary immunodeficiency and in those with cord blood transplant. Attributable symptoms were present in 12 patients (60%) concurrently with positive PCR. Clinical manifestations spontaneously resolved without treatment in most cases, concomitantly with a decrease in viral load.HHV-6 reactivation during allogeneic HSCT is common. HHV-6 reactivation should be considered in patients with graft-vs-host disease-like rash, onset of CNS symptoms, delay in engraftment, and in patients after cord blood transplantation.

Aim: To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS). Methods: NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy. Results: Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29–9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24–4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54–10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32–6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03–4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%. Conclusion: Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis.

Reported here is an outbreak of 21 cases of Q fever that were diagnosed during 5 months in the spring and summer of 2001 at Rambam Medical Center, Haifa, Israel. An epidemiological investigation and a case-control study were conducted to identify risk factors associated with acquisition of the disease in this outbreak. Patients were more likely than controls to live in Krayot (a large suburb of Haifa) (76.2% vs. 41.5%; p=0.005), to have more contact with animals (usually pets) (66.7% vs. 26.9%; p=0.007), and to consume more unpasteurized dairy products (23.8% vs. 0%; p=0.01). The Krayot suburb is an entirely urban area, but several livestock facilities are located in its close vicinity, and some of them have been reported to harbor Q fever. Although the patients did not recall having had direct contact with farm animals, the results suggest the presence of livestock facilities in such close proximity to a residential area may cause urban outbreaks of Q fever.

To evaluate the use of a rapid strip test for the quick evaluation of sputum quality.Prospective, double-blind study. Sputum and saliva samples were collected. Sputum quality was assessed by the presence of polymorphonuclear neutrophils (PMNs) and squamous epithelial cells (SECs) per low-power (microscopic) field (LPF) [x10 objective]. Sputum was defined as follows: (1) informative (ie,25 PMNs and10 SECs per LPF); (2) semi-informative (ie,25 PMNs or10 SECs per LPF, but not both); or (3) uninformative (ie,25 PMNs and10 SECs per LPF). The first two levels were considered to be "sputum" and the third one was considered to be "nonsputum." The quality of the sputum was compared to results obtained using a rapid strip test (Combur-Test; Roche Diagnostics; Basel, Switzerland) for specific gravity (SG), pH, leukocyte esterase (LE) activity, and levels of nitrites, protein, glucose, and erythrocytes. A Kruskal-Wallis test was used to compare the three levels of sputum quality and the rapid strip test. A Mann-Whitney test compared sputum and nonsputum to the rapid strip reagents. Pearson correlation and kappa tests were used to assess correlation. Receiver operating characteristic was used to calculate the best cut-point values, and the sensitivity and specificity of these values were calculated.Eighty-two samples were included, with 61 samples from hospitalized patients and 21 samples from healthy volunteers. The best predicator of sputum quality was the SG of the reagent. Using an SG threshold definition of1.01, the sensitivity was 86.8% and the specificity was 75.9%. The specificity of protein, glucose/= +1, and LE levels were relatively low. No relationship was found between the results of the reagent strip test for pH, nitrites, and erythrocytes, and the sputum quality.Using an SG threshold definition of1.01, the rapid reagent strip test has been shown to be a sensitive test for the evaluation of sputum quality, which can be useful when facilities for sputum cytology are not available.

The possible association of pseudotumor cerebri and varicella infection was previously mentioned in a few case reports. In those cases, the history and clinical features of active varicella were obvious, and signs were directly related to the varicella infection. We describe three immunocompetent children with pseudotumor cerebri as the only manifestation of Varicella zoster virus reactivation, with a review of the literature. We suggest considering Varicella zoster virus in children with pseudotumor cerebri, even in the absence of a history of recent varicella infection.

Aim The precise role of the influenza virus in the morbidity of hospitalised paediatric pneumonia cases is unknown. We identified how many cases hospitalised during the 2009 pandemic had influenza-associated pneumonia and assessed their severity. Methods Children admitted to three Israeli medical centres during the 2009 influenza pandemic with radiologically confirmed pneumonia were prospectively screened for influenza. We compared the clinical, laboratory and radiologic findings for positive and negative cases. Results The pandemic H1N1 virus was detected in 89 (30%) of the 297 patients hospitalised for pneumonia and 55% of the Paediatric Intensive Care Unit admissions for pneumonia. There were no significant differences in the rates of underlying disease between the two groups. Logistic regression analysis revealed that children with pandemic H1N1 virus-associated pneumonia had significantly increased disease severity than those without, with a higher incidence of hypoxemia (41.6% versus 24%) with a relative risk (RR) of 2.2, higher rate of paediatric intensive care unit admission (16.9% versus 5.8%, RR of 2.7) and higher rate of mechanical ventilation (10.1% versus 2.4%, RR:4.4). Conclusion During the 2009 influenza pandemic, 30% of children hospitalised for pneumonia had the influenza infection and these children displayed increased disease severity.

Thirty-six term neonates born after maternal intrapartum fever, with premature rupture of membranes18 hours and unknown maternal group B Streptococcus status had blood samples for complete blood count, C-reactive protein, culture, and 16S rRNA gene polymerase chain reaction amplification. Only 2 neonates were symptomatic and none had leukopenia, C-reactive protein1.0 mg/dL, bacteremia, or positive polymerase chain reaction.

Subgaleal hematoma (SGH) is an infrequent finding in neonates, occurring mostly after vacuum extraction deliveries. SGH can cause anemia, hypovolemic shock, and death. To date, only one case of neonatal infected SGH has previously been reported. We describe a term neonate with severe polymicrobial infection complicating SGH, including anaerobic bacteria, and with unique imaging features.

A gram-positive rod with a restriction pattern closely related to the published nucleotide sequence ofMycobacterium mucogenicumwas isolated from 6 of 45 units of peripheral blood stem cell products. The source of the contamination was traced to ice cubes used in processing the peripheral blood stem cell products. Substituting reusable ice trays for ice from an ice machine terminated the outbreak.

We tested the safety and immunogenicity of the new recombinant hepatitis B virus (HBV) vaccine produced via expression of the Pre-S1, Pre-S2 and S protein components of the hepatitis B surface antigen (HBsAg). A reduced dose (2.5 micrograms) of the vaccine (Bio-Hep-B) was tested in children aged 4-9 years and was compared to a 10 microgram dose of a licensed vaccine (Engerix-B) in a randomized manner. Both vaccines were administered in 3 doses (0, 1 and 6 month intervals). Adverse events were collected 5 days following each vaccination by a diary card provided to the parents. Immunogenicity was tested by measuring anti-hepatitis B surface antibody (anti-HBs). A total of 217 children were enrolled (162 in the Bio-Hep-B group and 55 in the Engerix-B group). Total adverse events were observed in 35% of the Bio-Hep-B group and 33% of the Engerix-B group, with no differences when each of the potential adverse events was considered. Titers were within the expected range (geometric mean titers post dose 1, 2 and 3 were 45.8, 8360.2 and 1445.7, respectively, for Bio-Hep-B and 36.3, 10316.1 and 1898.7, respectively, for Engerix-B). A trend toward better immunogenicity with Bio-Hep-B was observed at early visits when measured by both seroconversion (anti-HBs > or = 2.1 mIU ml-1) rate and seroprotection (anti-HBs > or = 10 mIU ml-1) rate; however, statistical significance was not reached. We conclude that in children, Bio-Hep-B vaccine at a reduced dose was as safe and as immunogenic as Engerix-B given at the regular pediatric dosage.

Legionnaires' disease is a rare cause of community acquired pneumonia in children and is exceedingly rare in infants and neonates. We describe a case of a 15 years old female, with lymphoblastic leukemia and legionella pneumophila pneumonia. Diagnosis was made by specific culture and polymerase chain reaction method from sputum and bronchoalveolar ravage specimens. Treatment was prolonged because of slow resolution and the fact that she underwent bone marrow transplantation. This emphasizes the importance of considering this rare entity in cases of severe pneumonia, especially in the immunocompromised host.

Primary cutaneous nocardiosis is an infrequent infection among children, generally affecting immunocompromised hosts. It is caused by Gram positive bacteria, partially alcohol and acid resistant which are saprophytes of the soil, water and organic matter. In most cases the causal agent enters through inhalation, and hematogenous dissemination may occur mainly among the immune compromised patients. Direct cutaneous inoculation is less frequent, especially among children. We report an 8-year old female who lives in an urban house with a small garden, who presented with an ulcer on her right shin accompanied by surrounding cellulitis, pain, swelling and fever. The patient's medical history was unremarkable, with no exposure to animals or travelling, except for rafting on the Jordan River the previous week. Culture from the ulcer grew Nocardia brasiliensis, and she recovered after 8 weeks of therapy with trimethoprim-sulphamethoxazole.

Diagnosis of Cryptosporidium is made by the identification of oocysts in stool specimens. Screening in field studies relies mainly on acid-fast staining followed by microscopic examination. The more sensitive immunofluorescent antibody (IFA) staining method is time-consuming, may involve technical difficulties, and is extremely costly as a screening procedure in field studies. We evaluated the diagnostic utility of a commercially available enzyme immunoassay (EIA), which detects Cryptosporidium-specific antigen, in 204 unprocessed stool specimens obtained from patients less than three years of age from a field study in southern Israel. When compared with the routine screening procedure applied in this field study (screening by acid-fast staining and microscopy after concentration, and confirmation of positive results by IFA), both the sensitivity and specificity were 98%. Of 139 specimens negative by microscopy, 13 (9.3%) were positive by the EIA. Eleven of these were confirmed by inhibition with antibody to Cryptosporidia-specific antigen. The EIA is an important tool for identifying Cryptosporidium in fecal specimens in field studies since it is sensitive, specific, simple to use, and unaffected by the presence of a preservative.

Invasive disease caused by Streptococcus pneumoniae (SPn) is common among young children. Severe sepsis can be seen among those with primary or secondary immunodeficiency states. The absence of a spleen is a well-known risk factor for severe and overwhelming pneumococcal sepsis, as well as other encapsulated bacteria (e.g. Haemophilus influenzae type b (Hib), or Neisseria meningitidis). The most common cause of asplenia is surgical removal of the spleen (after trauma or as a treatment for various hematological conditions). Dysfunction of the spleen can also be seen in sickle cell disease, with high risk of invasive bacterial diseases. Primary congenital asplenia is rare. Congenital asplenia can be a part of Ivemark syndrome which is accompanied by other malformations. Isolated congenital asplenia is exceedingly rare. These patients can present with severe sepsis, meningitis or even sudden death. Overall, 31 cases have been reported, among them 17 were familial and the rest sporadic. The genetic bases for this rare life-threatening malformation are not known. The authors describe a one year old patient, presented with severe pneumococcal sepsis and multisystem organ failure. Isolated congenital asplenia was demonstrated. The child recovered and is being treated according to the recommendations for adults with asplenia.

Objectives To describe the clinical characteristics of children hospitalized with 2009 influenza A(H1N1) infection in Israel and the risk factors associated with this infection. Design Prospective collection of data on children hospitalized with 2009 influenza A(H1N1) infection. Setting Seven medical centers around Israel. Patients From July 12, 2009, to December 24, 2009, all patients 18 years or younger hospitalized with acute respiratory or acute unspecified febrile illness were screened for 2009 influenza A(H1N1) virus by reverse transcription–polymerase chain reaction. Intervention Prospective data collection for patients with confirmed infection. Main Outcome Measures Clinical characteristics of patients and hospitalization rates. Results The mean age of 478 patients studied was 6.1 years. Forty-two patients (8.8%) were admitted to the pediatric intensive care unit; 3 patients (0.6%) died. The most frequent clinical presentations were pneumonia, influenza-like illness, wheezing exacerbation, and convulsions. Predisposing underlying illnesses were detected in 48.7% of patients. Patients with metabolic and neurologic disorders were at highest risk for severe complications (relative risk, 6.5 and 2.9, respectively). In addition, patients with cyanotic heart lesions and infants 3 months or younger who were born at 33 weeks' gestation or earlier tended to require higher rates of mechanical ventilation. The hospitalization rate for 2009 influenza A(H1N1) was 0.7 per 1000 children. The mortality rate was 3.6 per 1 000 000 children. Conclusions The severity variables for 2009 influenza A(H1N1) were similar to the figures reported for seasonal influenza. Patients with underlying metabolic and neurologic metabolic disorders and presumably patients with cyanotic heart lesions and infants born prematurely are at highest risk for severe complications following 2009 influenza A(H1N1) infection.

Background and Aims: Mycobacterium mucogenicum (MM) is a rapidly growing nontuberculous mycobacterium that is commonly identified in tap water that can rarely cause bacteremia. We describe an outbreak of MM bacteremia among pediatric hematology-oncology patients. Methods: Charts of children with MM bacteremia were retrospectively reviewed. Demographic data, underlying conditions, central venous catheter (CVC) type, duration of bacteremia, and treatment were retrieved. Epidemiologic investigation was conducted during the outbreak including environmental sampling. Results: During an 8-month period (September 2005-May 2006), 8 patients aged 1.5 to 17 years had MM bacteremia. Seven patients had underlying malignancy and 1 with thalassemia major had bone marrow transplantation. The mean number of positive blood cultures was 4.2 (1-11) per patient. Two patients received antibiotic treatment in addition to removal of CVC. All patients were cured. Almost 60 environmental samples were obtained from surfaces, ice, and municipal water supply. All were negative and no source was documented. Infection control measures included emphasis on guidelines for prevention of CVC-associated infections. No cases occurred before and after this outbreak. Conclusions: MM is a rare agent of CVC-associated bacteremia. Removal of the CVC may be sufficient for management of bacteremia. In the absence of definite source identification, reinforcement of standard infection control measures can be successful in containing outbreaks.

Anaerobic meningitis may occur alone, but is usually encountered as a complication of a brain abscess. In either case it is rare in a normal host. We present a 6-year old boy with anaerobic meningitis after missed penetrating trauma, stressing the need for a thorough investigation after head trauma.

Kingella kingae is a gram-negative coccobacillus, increasingly recognized as an invasive pediatric pathogen. To date, only few small series of invasive K. kingae infections have been published, mostly from single medical centers. A nationwide multicenter study was performed to investigate the epidemiologic, clinical, and laboratory features of children with culture-proven K. kingae infections.Clinical microbiology laboratories serving all 22 medical centers in Israel were contacted in a search for children aged 0 to 18 years from whom K. kingae was isolated from a normally sterile site, dating from as far back as possible until December 31, 2007. Medical records of identified patients were reviewed using uniform case definitions.A total of 322 episodes of infection were identified in 321 children, of which 96% occurred before the age of 36 months. The annual incidence in children aged4 years was 9.4 per 100,000. Infections showed a seasonal nadir between February and April. Skeletal system infections occurred in 169 (52.6%) children and included septic arthritis, osteomyelitis, and tenosynovitis. Occult bacteremia occurred in 140 children (43.6%), endocarditis in 8 (2.5%), and pneumonia in 4 (1.2%). With the exception of endocarditis cases, patients usually appeared only mildly ill. About one-quarter of children had a body temperature38 degrees C, 57.1% had a blood white blood cell count15,000/mm, 22.0% had normal C-reactive protein values, and 31.8% had nonelevated erythrocyte sedimentation rate.K. kingae infections usually occur in otherwise healthy children aged 6 to 36 months, mainly causing skeletal system infections and bacteremia, and occasionally endocarditis and pneumonia. Clinical presentation is usually mild, except for endocarditis, necessitating a high index of suspicion.

Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT in Israel is not known.To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection.Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records.Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03).In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)

The genomes of spotted fever group rickettsiae isolated in different geographical areas of Israel (two from ticks and four from humans, obtained over a span of 20 years) were studied by polymerase chain reaction (PCR) and restriction endonuclease fragment length polymorphism (RFLP) analysis. The human isolates were obtained from patients suffering from rickettsial disease of different degrees of severity. The PCR products obtained with five pairs of oligonucleotide primers (two primer sets derived from the 190-kDa polypeptide gene and three from the 120-kDa polypeptide gene) and cleaved with restriction endonucleases were used to study the Israeli isolates and reference Rickettsia conorii isolates. Subtle differences between the PCR-RFLP patterns of Israeli isolates and the two R. conorii reference strains (Moroccan and no. 7) were seen when the PCR products derived from the 190-kDa gene-derived primer sets were digested. All of the Israeli isolates were identical by RFLP analysis using all of the primer sets. This study showed that the Israeli spotted fever group isolates (from both ticks and humans) were genetically homogeneous by the criteria used in this study, despite the time and location differences in their original isolation, and different as a group from R. conorii.

Acute bronchiolitis (AB) is a significant indication for hospitalization during the winter period. Underlying conditions increase risk for severe manifestations.To estimate the burden and outcomes of AB in northern Israel.A prospective study was performed between 1.12.2005 - 31.3.2006. Previously healthy children younger than 2 years of age, hospitalized with the diagnosis of AB, in three hospitals in northern Israel, were included in this study.Overall, 465 children (93%) out of 500 children who were hospitalized due to AB and comprised 18% of all hospitalizations during the study period, were included. A pathogen was identified in 91% of cases. A single pathogen was identified in 243 (52%) cases; 2-4 pathogens were found in 176 (39%) children. Common pathogens were respiratory syncytial virus (RSV) and Rhinovirus in 346 (75%) and 129 (28%), of which 192 (41%) and 37 (8%) were sole pathogens respectively. Complete data were available for 390 (82%) children, of whom 78% were younger than 6 months. Patients were hospitalized for 4 +/- 4.4 days; 15 children were treated in intensive care. There was one mortality. An X-ray was performed in 94% of cases. Most children were treated with multiple regimens including intravenous fluids, O2 supplement, physiotherapy, bronchodilators, steroids and antibiotics. Bronchiolitis was attributed to 18% of hospitalizations. On a national scale, assuming that the policy of hospitalization is similar, 4100 children were hospitalized due to AB. This reflects 4% of all hospitalized children a year in Israel and attributing to 16,400 hospitalizations.AB is associated with a huge burden, during a short period of the year, on pediatric departments, mainly attributed by infants younger than 6 months of age. The development of effective vaccine against RSV may significantly reduce the burden of morbidity.

Acute bronchiolitis (AB) is a common disease of young children with peak incidence during the winter season. Respiratory syncytial virus (RSV) is a major causative organism, yet recent relatively small sized studies have suggested an increased role of other organisms as sole or codetected organisms. The aim of this study was to assess the prevalence of sole- and mixed-organisms infections in hospitalized children with AB, using combined antigen-based and polymerase chain reaction assays (PCR).Sputum or nasal wash specimens obtained from 490 previously healthy childrenor =2 years of age hospitalized with AB between December 1, 2005 and March 31, 2006 were tested: (1) For RSV, by rapid antigen detection test; (2) For RSV, influenza A, B, Parainfluenza 1 to 3, and adenovirus antigens by direct fluorescent assay; (3) For influenza A and B, RSV, Parainfluenza 1 to 3 viruses RNA by reverse transcription (RT) PCR assay; (4) For human metapneumovirus and rhinovirus RNA by RT real-time PCR assay; (5) For adenovirus, and Bordetella pertussis DNA by conventional PCR assays; (6) For human bocavirus DNA by real-tine PCR assays.At least 1 organism was detected in 465 (91%) children. In 283 (61%), 117 (25%), and 23 (5%) children, 1, 2, and 3/4 organisms were detected, respectively. The most commonly detected organism was RSV, detected in 76%, and as a sole organism in 49%. Rhinovirus, human metapneumovirus, influenza virus A, bocavirus, Bordetella pertussis, and adenovirus were detected as a sole organism in 7%, 2.1%, 1%, 0.6%, 0.6%, and 0.2% of the children, respectively.Respiratory organisms were detected in the majority of the children, of whom about one third suffered from mixed organism infection. RSV was the most prevalent sole detected organism. The relevance of all other organisms may be much less than previously suggested.

To examine the efficacy and safety of a new topical anesthetic containing a disinfection ingredient (LidoDin cream) in reducing the pain associated with venipuncture by comparing it with the proven eutectic mixture of lidocaine 2.5% and prilocaine 2.5% (EMLA cream).A single-blind, randomized, controlled trial was conducted on a study population consisting of a convenience sample of patients aged 12 to 16 years who presented at our Emergency Department between November 2007 and April 2008. The Visual Analog Scale (VAS) was used for pain assessment. Before the study, the bactericidal effect of the LidoDin cream on skin flora was tested.Twenty patients were enrolled to each arm of the study. Mean patient age was 13.6 years for the LidoDin group and 14.12 years for the EMLA group (P=0.347). Male patients accounted for 55% of the patients in the LidoDin group, compared with 40% in the EMLA group (P=0.527). Skin reaction scores of the LidoDin group for erythema and edema were not statistically different than those of the EMLA group (P=0.73 and P=0.75, respectively). Patient VAS scores and nurse VAS scores of the LidoDin group were not statistically different than those of the EMLA group (P=0.57 and P=0.93, respectively).This pilot study demonstrated that LidoDin and EMLA seem to be equally safe and effective topical anesthetics for venipuncture. Future studies are planned to determine, if LidoDin reduces the rate of local skin infection in patients treated with multiple daily subcutaneous injections of medications.

According to the U.S. Centers for Disease Control guidelines, prolonged rupture of membranes mandates intrapartum antimicrobial prophylaxis for group B Streptococcus whenever maternal GBS status is unknown.To evaluate the local incidence, early detection and outcome of early-onset GBS sepsis in neonates born at 35-42 weeks gestation after PROM to women with unknown GBS status who were not given intrapartum antimicrobial prophylaxis.During a 1 year period we studied all neonates born beyond 35 weeks gestation with maternal PROMor =18 hours, unknown maternal GBS status and without prior administration of IAP. Complete blood count, C-reactive protein, blood culture and polymerase chain reaction amplification of bacterial 16S rRNA gene were performed in blood samples collected immediately after birth. Unfavorable outcome was defined by one or more of the following: GBS bacteremia, clinical signs of sepsis, or positive PCR.Of the 3616 liveborns 212 (5.9%) met the inclusion criteria. Only 12 (5.7%) of these neonates presented signs suggestive of sepsis. PCR was negative in all cases. Fifty-eight neonates (27.4%) had CRP1.0 mg/dl and/or complete blood count abnormalities, but these were not significantly associated with unfavorable outcome. Early-onset GBS sepsis occurred in one neonate in this high risk group (1/212 = 0.47%, 95% CI 0.012-2.6).In this single-institution study, the incidence of early-onset GBS sepsis in neonates born after PROM of 18 hours, unknown maternal GBS status and no intrapartum antimicrobial prophylaxis was 0.47%.

Drug utilization in the in-patient setting can provide mechanisms to assess drug prescribing trends, efficiency and cost-effectiveness of hospital formularies and examine sub-populations such as children for which prescribing habits are different from adults. Objectives: The aim of this descriptive study was to analyze general medication utilization patterns and costs excluding antimicrobials prescriptions and to compare two pediatric admission units in a tertiary care university hospital. Methods: The total number of admitted children was 1,521 and 1,467 for the A and B admission units, respectively. The electronic data from 252 and 253 hospitalized children in the A and B admission unit were prospectively screened for general medication prescriptions, children on antimicrobials were excluded from the analysis. Their electronic charts were viewed once weekly from October 15, 2007 up to April 7, 2008 using the prescription-point prevalence method. One medication was considered to be one prescription. Results: The general medications prescription number was 790 for 94 children (8.4 prescription/patient) in A and 959 for 88 children (10.9 prescription/patient) in B (p=0.02). The general medications defined daily dose (DDD) and drug utilization 90% (DU90%) index were 2,509.63, 2,259 for A; and 6,110.35, 5,499 for B, respectively. The DU90% index placed salbutamol inhalation with 835 DDD and sodium heparin with 2,102 DDD in the first place for the A and B admission units, respectively. A net increment in medication cost was registered according to the calculated cost from the depicted DU90% when the A (20,263 NIS) and B (6,269 NIS) admission units were compared (p=0.04). Conclusions: A significant difference in the prescription utilization of general medications was shown between the A and B admission units. The A admission unit had lower prescriptions measured by the DU90% index with higher medication cost. Potential drug-drug interactions were depicted in 18 (19%) and 17 (19%) subjects in the A and B admission unit, respectively.

Voiding cystourethrogram is performed 3-6 weeks after urinary tract infection. This prolongs the interval of prophylactics, reducing the likelihood of having to perform the procedure.To investigate the yield and potential risks/benefits of early compared to late performance of VCUG after UTI.We conducted a prospective study of 84 previously healthy children5 years old admitted from October 2001 to November 2002 with first documented UTI. We then divided the 78 patients who had VCUG into two groups and compared them to a control group: group A--49 children in whom VCUG was performed within 10 days, group B--29 children in whom VCUG was performed10 days after UTI, and a historical control group C--82 children in whom VCUG was performed4 weeks following UTI.VCUG was performed in 48/48 (100%), 6/35 patients (17.1%) and 34/116 patients (29.3%), and vesicoureteral reflux was demonstrated in 38.8%, 37.9% and 39% in groups A, B and C respectively. No significant difference was found between these groups in terms of incidence of VUR and severity and grading of reflux within each group. One case of UTI secondary to VCUG occurred in a patient in whom the procedure was performed 4 months after the diagnosis.Performing VCUG early does not influence the detection rate, severity of the VUR, or risk of secondary infection; it shortens the period of prophylactic use and increases performance rate of VCUG, thereby minimizing the risk of failure to detect VUR. The traditional recommendation of performing VCUG 3-6 weeks after the diagnosis of UTI should be reevaluated.

We conducted a 1-year prospective study in the Negev region of southern Israel to determine the epidemiologic and clinical patterns of rotavirus diarrhea. A total of 605 patients were studied, 392 Bedouins and 213 Jews, 441 of whom had diarrhea (449 episodes) and 164 did not. Rotavirus was the most common organism detected in children with diarrhea (63 of 444; 14%) but was rarely found in controls (3 of 163; 2%) (P less than 0.001). In 22% (12 of 54) of the rotavirus-positive patients, at least one other organism was also detected. The rate of rotavirus detection decreased as age increased, from 18% in the first year to 8% in the third year of life. Hospitalization with rotavirus diarrhea occurred more frequently in the summer. However, during winter, when diarrhea was less prevalent in the community, the proportion of cases associated with rotavirus was higher. Compared with controls, malnourished children were more likely to be hospitalized. However, rotavirus was detected in similar proportions among well-nourished and malnourished cases with diarrhea. The most prevalent rotavirus serotype was type 1 (in 69%), followed by types 4 and 2 (18 and 13%, respectively). We estimated that during the study period, approximately 2% of all Bedouin infants vs. only 0.2% of Jewish infants were hospitalized with rotavirus disease in their first year of life. Clinical signs and symptoms and stool appearance were not useful in predicting rotavirus detection. Malnutrition seems to be an important indicator of disease severity, which may explain why the toll of rotavirus-associated morbidity and mortality is particularly high among children in developing countries.

We describe the cases of three children with encephalitis associated with Coxiella burnetii infection. Neurologic features ranged from status epilepticus and coma to headache and pseudotumor cerebri syndrome. Patients had good response to antibiotic treatment with doxycycline and recovered fully. Q fever should be included in the differential diagnosis of children with encephalitis, and routine serological testing should be considered, especially in endemic areas.

Whenever suspicion of late-onset sepsis (LOS) is raised, sepsis workup is performed and empiric anti-microbial therapy (AMT) is initiated. However, the prescribed AMT may often be inappropriate for the eradication of the causative pathogen.To evaluate the clinical, interventional and laboratory predictors of LOS, and to evaluate the appropriateness of empiric AMT in late-onset neonatal sepsis.The medical records of all neonates admitted to a tertiary NICU during a 1-year period were retrospectively reviewed. Out of 352 infants admitted, 84 neonates developed 96 suspected septic events beyond 3 days of age and comprised the study population. LOS was defined as clinical signs of sepsis accompanied with positive blood and/or urine and/or CSF cultures obtained at the onset of the septic event. For each infant, we collected demographic and perinatal characteristics, neonatal diagnoses and interventions, clinical signs and laboratory abnormalities at onset of sepsis, the AMT instituted, and microbiological data.Of the 96 events of suspected LOS, 26 (27.0%) positive blood cultures, w ith coagulase-negative St aphylococcus (CoNS), Klebsiella and Candida accounting for 22/ 26 (84.7%) of these events. In four out of 75 events (5.3%), urine culture was positive. Logistic regression multivariate analysis showed that birth weight (OR=0.9, 95% CI: 0.82-0.99; p=0.031), apnea/bradycardia (OR=3.16, 95% CI: 1.08-9.25; p=0.036), and platelet count100,000/mm3 (OR=7.04, 95% CI: 1.21-40.9; p=0.03) were significantly associated with LOS. Out of 29 proven septic events, 14 (48.3%) had received AMT within 3 days prior to onset of LOS. In 26/29 (89.7%) of proven septic events, empirical AMT was started after sepsis work-up, mostly vancomycin 18/29 (62.0%), imipenem 14/29 (48.3%), and amphotericin B 9/29 (31.0%). Out of the 26 proven septic events treated with empiric AMT, the causative pathogen was sensitive to the prescribed AMT in 24 (92.3%) of the cases.Significant predictors of LOS include lower birth weight, apnea/bradycardia and thrombocytopenia. Empirical AMT was initiated in 90% of proven septic events and was appropriate in 92.3% of these cases. When confronted with suspected LOS in the NICU setting, empiric coverage of CoNS, Klebsiella and fungi should be considered, based on the infant's condition and on local microbiological data.

We compared PCR with blood cultures in the diagnosis of neonatal staphylococcal sepsis. Significant association was observed between PCR-based and culture-based diagnosis of staphylococcal bacteremia. Positive and negative predictive values for PCR were 100% and 98%, respectively. These data indicate that PCR may serve as a useful adjunct for the rapid diagnosis of staphylococcal sepsis.

Whereas the diagnosis of classical pertussis has traditionally been based on clinical criteria, increasing numbers of atypical presentations suggest the need for an extensive laboratory-based approach.To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.PCR and culture identified 41% and 7% of patients with B. pertussis, respectively (P0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P0.001) and post-vaccinated groups (P0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.

Puncture wounds in the feet of children present a clinical dilemma.To evaluate our approach, we reviewed the charts and all available images of 80 children admitted to our institution because of plantar punctures from 1988 to 1999.The charts of 80 children were reviewed retrospectively.Three groups of patients were found: 59 with superficial cellulitis, 11 with retained foreign bodies, and 10 with osteoinyelitis and/or septic arthritis. There was a significant presentation delay in patients from the second and third groups. Most common organisms were Staphylococcus aureus or Group A Streptococcus. Of the 80 children, 34 were treated surgically and 46 were treated with antibiotic therapy alone. All patients with osteomyelitis and septic arthritis were re-examined; at follow-up, all but one were asymptomatic apart from residual radiologic sequelae in four.Patients with an established infection 24-36 hours after a plantar puncture should be admitted to hospital for parenteral antibiotic therapy. Delayed presentation is a significant marker for deep-seated infection. Further infection or relapse after initial improvement suggests the presence of osteomyelitis or a retained foreign body. A bone scan is advisable in all patients with suspected osteomyelitis: a positive bone scan necessitates aggressive early debridement combined with appropriate antibiotics; while negative bone scan, X-ray and exploration suggest that the infection is due to a foreign body, which can be detected by computed tomography.

Factors influencing the oral flora of premature infants have not been adequately investigated.To investigate the effects of gestational age and of anti-bacterial therapy on the oral flora of premature infants.Oral cultures were obtained at age 1 day and age 10 days from 65 premature infants, divided into three groups: a) 24 neonates of 30-34 weeks gestation who did not receive ABT, b) 23 neonates of 30-34 weeks gestation who received ABT, and c) 18 neonates30 weeks gestation who received ABT.Oral bacterial colonization increased from day 1 to day 10 of life. In 24-34 week neonates, gestational age did not affect early bacteremia or oral colonization at birth. Neither gestational age nor ABT affected late bacteremia or oral colonization at day 10. In 30-34 week neonates with ABT, the oral flora consisted mainly of non-Escherichia coli gram-negative bacteria, whereas those who did not receive ABT grew mainly alpha-hemolytic streptococci, Klebsiella pneumoniae and E. coli. In neonates30 weeks who received ABT the oral flora were mainly coagulase-negative staphylococci. Oral colonization with anaerobes was zero and colonization with fungi was minimal.Acquisition of oral bacteria rose from day 1 to day 10 of life, regardless of gestational life or ABT. On day 10 of life, the spectrum of oral bacterial flora changed following ABT and consisted mainly of coagulase-negative Staphylococcus and non-E. coli gram-negative bacteria. Oral colonization showed few fungi but no anaerobes. These microbiologic observations merit attention when empirical anti-microbial therapy is considered in premature infants suspected of having late-onset sepsis.

To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia.Prospective cohort study.A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997.Of 137 episodes of positive blood cultures for CNS, 41 (30%) were considered as true infection. Twenty-seven of 119 episodes associated with only 1 blood culture positive for CNS (23%) met the definition of infection as compared with 14 of 18 episodes (78%) associated with 2 or more blood cultures positive for CNS (P.001). Methicillin resistance was significantly more frequent among Staphylococcus epidermidis isolates of episodes of true bacteremia than of episodes of contamination (15 of 22 [68%] vs. 11 of 33 [33%], respectively; P =.02). S hominis was isolated only in episodes considered as contamination (P =.01). It was estimated that CNS represents 24% of all nosocomial bloodstream pathogens. When CNS were isolated in the first 48 hours of hospitalization, an intravascular device was more frequently associated with episodes of true bacteremia than in those considered as contamination (7 of 7 [100%] vs. 10 of 57 [18%], respectively; P.001). The mortality rate among patients with true CNS bacteremia was 16%.Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

Febrile neutropenia (FN) is a common complication among children undergoing chemotherapy for hematologic malignancies. A microbial agent is identified in 15–30% of these episodes. Recently, several studies reported a high incidence (25% -60%) of respiratory viral infections (RVI) in children with FN, using RT- PCR analysis. Implementation of routine RVI workup in children with FN was suggested, in order to minimize the overuse of antibiotics. However, data on the incidence of RVI in children with persistent FN (PFN) is meager. In the setting of PFN, invasive fungal infection (IFI) is a major concern. The incidence of IFI among children with hematologic malignancies varies with clinical settings, although most children who present with PFN do not have IFI eventually. Yet, most international guidelines indicate empiric initiation of antifungal therapy after 4-7 days of FN. Alternatively, a “preemptive” approach using currently available diagnostic modalities (CT and serum specific biomarkers) was suggested in adult patients. In children with PFN, however, this workup resulted only in a modest decline in the antifungal treatment rate. Therefore, there is a growing need to enhance diagnostic resolution, in order to stratify pediatric patients according to their risk for IFI, and minimize the overuse of antifungal drugs, imaging, and invasive procedures. To the best of our knowledge, there are no studies comparing the incidence of RVI to that of IFI in the setting of PFN. Based on previous published data, we hypothesized that RV infection is a significant cause of PFN in children with hematologic malignancies, and that IFI is the cause in a minority of cases. We further aimed to investigate whether detection of RVI, as the cause of PFN in these children, would affect their risk of IFI. For that purpose, we analyzed the clinical charts of children (38oc, for >96 hours and ≤500ANC/µl) and documented PCR results of RV. Patients were considered positive for IFI if they had ‘possible’, ‘probable’ or ‘proven’ infection according to the revised EORTC definition (2008). RVI were detected in nasopharyngeal aspirates using RT-PCR and included: RSV, Influenza A/B, H1N1, Parainfluenza 1/2/3, HMPV, Adenovirus and HHV-6. Additional data included age and gender, specific hematologic malignancy, total number of neutropenia ( A total number of 75 PFN episodes were evaluable, representing 54 patients with ALL (HR n=18; SR n=23), AML (n=6), NHL (n=5) or Hodgkin’s (n=2). Of these, there were 31 episodes with RV-positive infections (41.3%). The most prevalent virus was RSV (29%), followed by Parainfluenza (26%) and Adenovirus (19%).There were 16 possible (21%), 2 probable (2.6%), and 2 proven (2.6%) episodes of IFI. Only in 3 episodes we detected co-infection of IFI (2 possible and 1 probable) and RVI. Multivariate analysis revealed that the total days of neutropenia and antibiotic therapy were independent risk-factors for IFI (p Children with PFN and RVI have a significantly lower risk for IFI. This observation may reduce unnecessary imaging and invasive procedures, antifungal treatment, and hospital expanses. Further studies are needed in order to establish whether RV-status can be implemented in the routine workup algorithm of PFN in children with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

Exfoliative skin diseases are rare in neonates. When caused by coagulase-positive Staphylococcus aureus, scalded-skin diseases such as staphylococcal scalded-skin syndrome (SSSS), bullous impetigo, and staphylococcal scarlet fever may develop. These diseases might cause significant complications and mortality. SSSS is caused by staphylococcal exfoliative toxins A or B, which split the granular layer of the skin, induce proteolysis, and might exhibit superantigen activities, such as epidermolysis and lymphocyte mitogenicity. We describe a 1378-g premature male infant who was born at 29 weeks' gestation and developed SSSS on day 3 of life, with no clinical signs of neonatal sepsis. After cultures from the lesion and bloodstream were obtained, intravenous cloxacillin therapy was started. Infection control measures were implemented instantly and included isolation of the infected infant, personnel handwashing with hexachlorophene, and placement of exposed neonates into a cohort. The initial lesion expanded and additional lesions appeared, but 12 hours after initiation of antibacterial therapy, the lesions ceased to proliferate. Cultures from scalded-skin lesions grew coagulase-positiveStaphylococcus aureus, whereas the bloodstream culture was sterile. The lesions resolved completely within 6 days, and the infant's subsequent course was uneventful. No similar skin lesions were noticed in other infants in the neonatal intensive care unit. We discuss recent advances in understanding the pathogenesis of neonatal SSSS, highlight the importance of early diagnosis and treatment, and stress the need for new adjunctive therapies for this disease.