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Objectives To analyze the results of a neonatal universal screen for congenital cytomegalovirus (CMV) using saliva real-time polymerase chain reaction (rt-PCR). Study design During one year (15/5/2011–15/5/2012), saliva was collected from 9845 infants (97% of 10,137 newborns). Viral DNA was extracted by Magna-Pure LC (Roche) and was tested for the presence of CMV IE and gB genes. Urine culture was collected from positive infants for confirmation. For all infants with congenital CMV maternal data were collected and head ultrasound, blood count, liver enzymes, retinal examination and auditory brainstem response testing were performed. Parents were notified in advance and had the option to avoid screening. The ethical committee approved retrospective analysis of the data. Results Fifty six infants (0.57%) had a positive saliva assay. Of these, 47 were confirmed by urine rt-PCR and culture, in another one maternal sero-conversion was documented during pregnancy (48 infants). Twenty-eight mothers (28/47, 60%) had primary infection during pregnancy, 14 (30%) had non-primary infection, and no serological data were obtained from five (10%). Four infants (8.5%), two with prenatal diagnosis of CMV and normal fetal brain imaging and two born to mothers sero-positive before pregnancy, exhibited symptoms related to CMV and were offered antivirals. Hearing impairment was diagnosed in two infants (late onset HI in one case). Conclusions Saliva rt-PCR assay is a feasible and effective means of universal neonatal CMV screening that can detect affected infants who might benefit from treatment and follow-up. The long-term clinical significance of screening and its cost effectiveness are yet to be determined.

A 13-year-old boy with severe haemophilia presented at the National Centre with gross swelling of his foot and infrapatella area, and reported that several months previously he had kicked a football and had instantly developed a bleed in his foot. Despite replacement factor the swelling failed to subside. He had ambulated for a while using crutches and when he eventually presented himself the X-rays revealed two separate pseudotumours. The patient underwent a transfemoral amputation.

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.

Objective: To determine the positive and negative predictive values of recalled exposure to chickenpox for identifying anti-varicella-zoster virus (VZV) seropositive parturient women. Methods: Blood samples were taken from laboring women during February 1998: All women completed questionnaires concerning a history of chickenpox in themselves and their children. Anti-VZV antibodies were determined by the immunofluorescent antibodies to membrane antigen (IFAMA) technique. Results: Three hundred and twenty-seven women formed the study population; 239 women (73.1%) recalled chickenpox in themselves or their children, of which 229 (95.8%) were seropositive for anti-VZV antibodies. Of the 88 women who gave a negative/uncertain history of chickenpox 82 (93.2%) were seropositive and 6 (6.8%) were seronegative. All 87 mothers who were certain their children had had chickenpox were seropositive, including all 16 mothers who had a negative personal history. Thus, a woman with a history of chickenpox had a positive predictive value of 95.8%, and a woman with a lack of history had a negative predictive value of 6.8% (sensitivity 73.6%, specificity 37.5%), while a positive history of chickenpox in a child had a positive predictive value of 100%. Conclusions: Most women with no known history of VZV infection have evidence of prior exposure by serologic testing. Moreover, 100% of women with a negative history who were exposed to VZV in their children were protected from the disease. Therefore, mothers exposed to VZV during pregnancy can be reassured that most likely they are protected. However, the practice of testing all pregnant women exposed to the disease should be continued.

To compare the placental transfer of maternal varicella-zoster (VZV) antibodies to preterm and term infants and to investigate antibody decay during the first 6 months of life in the preterm infants.Maternal and umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64 term (gestational ageor =37 weeks) and 49 preterm (gestational ageor =35 weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV antibody to membrane antigen was measured with the immunofluorescent technique.Preterm infants of gestational ageor =28 weeks had positive cord antibody and a geometric mean titer significantly lower than those in preterm infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%, respectively, P.001 for each, and 2.5 +/- 2.2 vs 10.5 +/- 2.4 and 12.6 +/- 2.4, respectively, P.001 for each). There was no difference between the preterm 29 to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm groups were1 and were significantly less than the fetal-maternal ratio in the term infants. The transfer of maternal antibodies to term infants was significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2 months of age, 25% of 29- to 35-week preterm infants and no preterm infantor =28 weeks had a positive titer. At 6 months of age, all preterm infants were seronegative, and the geometric mean titer in both groups declined to undetectable levels.Transplacental transfer of maternal VZV antibodies is diminished in preterm infants. VZV antibody levels are significantly lower in preterm infants born ator =28 weeks' gestational age compared with those in preterm infants 29 to 35 weeks' gestational age and term infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6 months of age or earlier; thus these infants appear to be susceptible to chickenpox before the scheduled 12-month vaccination.

This study was undertaken to determine whether the ability of group A streptococci to persist in the throat following antibiotic therapy corresponded with their capacity to adhere to and be internalised by epithelial cells. The study employed a HEp-2 cell model to examine the adherence and internalisation capacities of 42 strains (13 from asymptomatic patients with bacteriological eradication failure and 29 from patients with bacterial eradication). The adherence and internalisation efficiencies of strains from symptomless carriers were significantly higher. The average adherence efficiency of the carriers' strains was 53 (SEM 6)% versus 35 (SEM 5)% in control strains. The average internalisation efficiency of the carriers' strains was 13.4 (SEM 4)% compared with 4.4 (SE 1.6)% in the control group. The results are in agreement with the hypothesis that, in a significant number of cases, streptococcal internalisation might contribute to eradication failure and persistent throat carriage.

Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age.This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms foror = 36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication).A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B.Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.

OBJECTIVES—To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation. STUDY DESIGN—Middle ear fluid was obtained by tympanocentesis at enrolment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay. RESULTS—101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12 636 (23 317) v 5920 (7080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15 420 (15 418) v 6695 (5092) pg/ml). CONCLUSIONS—Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

AIMS To determine normal concentrations of 17α-hydroxyprogesterone (17OHP) for premature infants. METHODS 17OHP was measured in 66 consecutive premature infants once a week during the first month, and once every two weeks thereafter, until the age of 3 months. The 17OHP values in 100 full term healthy neonates on the third day of life served as controls. Blood was sampled on filter paper using a neonatal radioimmunoassay kit. Findings were correlated with gestational age, birthweight, mode of delivery, Apgar scores, presence of respiratory distress syndrome and intake of maternal steroids. RESULTS Mean 17OHP was raised at 7 days of age (138.9, 46.3, 53.3, 29.9 nmol/l, respectively, for infants whose gestational age was under 29 weeks, 29 to 30 weeks, 31 to 32 weeks, and 33 weeks and above). It fell sharply in the first two weeks after which it gradually decreased further, reaching 32.7, 23.6, 16.9, and 13.0 nmol/l, respectively, by the age of 90 days. The mean (SEM) 17OHP concentration in full term infants on day 3 of life was 17.8 (8.9) nmol/l. These values were independent of the presence and severity of respiratory distress syndrome and of prenatal maternal steroids. CONCLUSIONS The increased 17OHP concentrations found at birth fell to those found in term infants during the first three months of life in infants over 31 weeks of gestation. Postconceptional age is the most important factor determining 17OHP concentration.

Headache is a common complaint in children. Diagnosis of the type of headache and therapeutic approach is predominantly clinical based on a detailed history and physical examination. These data are often not available or informative in young children with headache, leading clinicians to look for diagnostic studies. We reviewed our experience with 53 children under the age of 5 years with headache. Of these, 42 (75%) children underwent neuro-imaging studies including CT scan (32 cases), MRI (10 cases), or both studies (6 cases). All were within normal limits except for two cases with a small arachnoid cyst and cerebellar hypoplasia respectively which were not directly related to the headache. Visual evoked potentials were performed in all children. There were no significant differences between the mean latencies of N(1)P(100) and N(2) of the children with clinically diagnosed migraine, however, the P(100)-N(2) amplitudes of children with migraine were significantly larger compared to those of children without migraine. Even in young children with headache, neuro-imaging studies have a very limited diagnostic value. Visual evoked potentials may also be used in this age group as a diagnostic tool, particularly when clinical symptoms are either unavailable or not characteristic.The diagnosis of migraine in young children remains clinical, based on history obtained from children and parents; however, visual evoked potentials may support the diagnosis in this age group.

In an ongoing prospective study, IL-1 concentrations were measured in 78 children (aged 3-36 months) with acute otitis media receiving antibiotics. Middle ear fluid IL-1 concentrations were determined using ELISA kits. Ninety-eight middle ear fluid samples were obtained by tympanocentesis at enrollment (day 1) and 43 samples were collected on days 4-5. Ninety-two pathogens were isolated in 77/98 samples obtained on day 1: 55 Haemophilus influenzae, 34 Streptococcus pneumoniae, 2 Moraxella catarrhalis and 1 Streptococcus pyogenes. Among 37 paired samples initially culture-positive, eradication of the pathogen was achieved on day 4-5 in 20 while pathogens were still present in 17. On day 1, IL-1 was detected in 61/77 (79%) culture-positive samples vs 9/21 (43%) culture-negative ones (P = 0.003). The mean +/- SD middle ear fluid concentration of IL-1 on day 1 was significantly higher in culture-positive (316 +/- 508 pg/ml) than in culture-negative samples (111 +/- 245 pg/ml) (P = 0.01). When paired samples were evaluated, IL-1 decreased on days 4-5 in 13/20 (65%) ears where bacterial eradication was achieved, but also in 11/19 (58%) with persistent or new infection. The mean IL-1 concentrations decreased on days 4-5 in the 20 samples from ears where bacterial eradication was achieved (330 +/- 460 vs 118 +/- 294 pg/ml, P = 0.1) but also in the 17 samples where it was not (465 +/- 660 vs 232 +/- 289 pg/ml, P = 0.02). No significant differences were found between day 1 and days 4-5 in the mean IL-1 concentrations measured in patients with H. influenzae vs S. pneumoniae or concomitant H. influenzae and S. pneumoniae. It was concluded that: 1) IL-1 was detected in the middle ear fluid of most patients with acute otitis media; 2) significantly higher IL-1 concentrations were found in patients with culture-positive than in those with culture-negative acute otits media; 3) IL-1 concentrations decreased on days 4-5 of antibiotic therapy, whether the pathogen was eradicated or not.

Summary Background The failure of antibiotic treatment to eradicate group-A streptococci in up to 30% of patients with pharyngotonsillitis is unexplained. Some strains of group-A streptococci can enter respiratory epithelial cells, where they would be inaccessible to antibiotics unable to penetrate the cell membrane, such as penicillins. The fibronectin-binding proteins, Fl and Sfbl, are needed for this process. We hypothesised, therefore, that an intracellular reservoir of group-A streptococci could account, at least partly, for failure to eradicate throat carriage, and that the presence of the gene for fibronectin-binding protein (F1) might be linked to the ability of a strain to persist in the throat after therapy. Methods We investigated the frequency of prtF1 -containing strains among 67 patients with pharyngotonsillitis. All patients were clinically cured, although 13 of them continued to carry group-A streptococci in the throat during or after therapy. To distinguish between persisting and recolonising strains, isolates from the 13 patients were serologically tested and compared by polymorphic DNA-amplification technique. Findings 12 (92%) of the 13 patients with symptomless carriage had prtF1 -containing strains in the throat, compared with 16 (30%) of the 54 patients with successful eradication (p=0·0001). Three of the 13 eradication-failure patients were recolonised with strains that differed from the pretreatment strains. Nine of the ten (90%) persisting strains carried prtF1 (p=0·0009). Interpretation Our findings suggest that protein-F1-mediated entry to cells is involved in the causative process of the carriage state.

Objectives: to determine whether non disposable aurioscope earpieces used in community paediatric clinics harbored pathogenic micro-organisms, and to explore primary pediatrician perception of the possibility of cross infection from contaminated aurioscope earpieces and of how their aurioscope earpieced are cleaned. Design: randomized survey. Setting: four community pediatric clinics. Materials: 42 pediatricians’ aurioscope earpieces were cultured on blood agar and mannitol-salt-agar plates by two methods: (1) The earpieces were rolled for 5 s onto blood agar plates (TSA+5% sheep blood, and a mannitol-salt-agar-plate). (2) The entire surface of the earpiece was swabbed with a sterile cotton tipped applicator moistened in sterile saline solution and was inoculated immediately onto a blood agar plate, and a mannitol-salt-agar-plate. The plates were incubated at 37°C for 48 h and examined for colony growth at 24 and 48 h of incubation. Culture results were recorded as mean numbers of colony-forming units (CFUs). Results: 36 from 42 (86%) of the aurioscope earpieces were colonized by micro-organisms. Heavily contaminated earpieces were found in six (14%). Staphylococci were isolated from 27 (64%) of the earpieces: 19 (45%) being Staphylococci aureus coagulase positive, 4 (9%) were methicillin resistant S. aureus (MRSA). Conclusions: Non disposable earpieces can harbor potentially pathogenic bacteria including MRSA. The increased trend for children with immundeficiency to be managed in an ambulatory setting, often by physicians who also work in hospital, might be a risk of spreading potentially serious infections to such patients. Non disposable earpices should be regularly disinfected to minimize the spread of infection.

The purpose of this investigation was to determine the predictive value of the ventilation index (VI) in children with acute respiratory distress syndrome (ARDS). We performed a 10-year retrospective chart review of children who were admitted to the Pediatric Intensive Care Unit with a diagnosis of ARDS. Acute respiratory distress syndrome was defined as acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin, and severe hypoxemia, defined as the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen of200 and a positive end expiratory pressure of 6 cmH2O or greater. Records of daily arterial blood gas results and ventilator settings were reviewed, and the ventilation index (VI=partial pressure of arterial CO2 x peak airway pressure x respiratory rate/1,000) was calculated each time the measurements were made. These values were correlated with outcome (survival or nonsurvival). The VI was not different at the time of diagnosis of ARDS in the patients who lived, compared with those who subsequently died. However, by 3 to 5 days after study entry, the VI of nonsurvivors was significantly higher than for survivors (P0.05). The VI for survivors remained between 30 and 35 throughout the study period, whereas the VI of nonsurvivors continued to increase with time. A VI of65 predicted death with a specificity and positive predictive value of90% on days 3 through 9. We conclude that the VI provides a reliable prognostic marker in children with ARDS, and its increase above 65 indicates a need for orderly intervention with alternative modalities of care.

The risk of bleeding among thrombocytopenic patients was evaluated using our new cone and platelet analyser (CPA) test. Using this test, adherence of platelets was quantitated on extracellular matrix and expressed as percent of surface coverage (SC) and the average size (AS) of aggregates. 42 thrombocytopenic patients with ITP (n=23), post chemotherapy (n= 12) and others (n= 7) were tested over a total of 82 visits. On each visit, complete blood count and CPA tests were performed and patients were evaluated for evidence of bleeding (found in 40 visits). Bleeding patients had significantly lower platelet counts (27.4 +/- 22.0 v 47.1 +/- 21.0 x 10(9)/l), lower haematocrit values (30.2 +/- 8.1 v 35.2 +/- 6.6%), lower MPV (6.83 +/-1.89 v 8.98 +/- 1.13 fl), and lower SC (4.87 +/- 3.95 v 10.33 +/-5.48%) and AS (33.99 +/- 14.94 v 52.9 +/- 24.34 microm2). Univariate analysis yielded platelet count < or =20.0 x 10(9)/l, MPV < or =8 fl, haematocrit

This study was designed to investigate the placental transfer of maternal poliovirus antibodies in full-term and pre-term infants. Two hundred healthy, Israeli born mothers and their infants, were enrolled immediately after birth. The study population comprised two groups: a full-term group of 150 mothers and their infants, and a pre-term group of 50 mothers and their infants (gestational age < 35 weeks). Maternal and umbilical cord blood samples were taken in all cases. Antibody titers against the three poliovirus serotypes and a polio virus type 1 strain that caused an outbreak in 1988 (epidemic strain 1) were measured by a microneutralization system. The proportion of individuals with protective titers against each of the poliovirus types tested was slightly lower in the infants compared with their mothers. When protection to all strains combined was tested, the difference between mothers and infants was significant (P < 0.05). Transplacental transfer to epidemic strain 1 was less effective--12% of the premature infants were not protected against it at birth. The geometric mean titers against poliovirus types 1, 3 and epidemic type 1 strain were significantly lower in the pre-term group than in the full-term group. In both the full-term and pre-term groups there were significant linear correlations between the maternal and neonatal antibody titers for each of the polio viruses tested. For all poliovirus types, the transfer of maternal antibodies to the full-term infant was significantly higher than the transfer of maternal antibodies to the pre-term infant (P < 0.001). Owing to diminished transfer of maternal antibodies, pre-term infants are at greater risk of poliovirus infection.

Mucormycosis is an uncommon infection caused by fungi of the order Mucorales, family Mucoraceae, and almost always occurs in individuals with predisposing factors such as diabetes mellitus, metabolic acidosis, or immunodeficiency states. Although mucormycosis is a rare infection in childhood, sporadic cases of skin infections have been described in young infants and older children; primary skin infection has been associated with multiple nosocomial outbreaks caused by contaminated elastic bandages. In all reported cases involving premature infants, the elimination of the infection involved surgical debridement. We report for the first time successful conservative treatment with intravenous amphotericin B in a premature infant with primary cutaneous infection caused by Rhizopus oryzae.

Congenital cytomegalovirus (C-CMV) infection affects 0.4-2% of newborn infants in Israel, most of whom are asymptomatic. Of these, 10-20% will subsequently develop hearing impairment and may have benetitted from early detection by neonatal screeing.To retrospectively anaIyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel, Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood.CMV DNA was detected by rt-PCR performed on infants' cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation.During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further Investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen infants (82%) would not otherwise have been diagnosed.The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

Eleven articles are included in this special issue of Harefuah dedicated to pediatric infectious diseases. Herein, they present the problems and dilemmas pediatricians, as well as general practitioners, face in current practice. In spite of tremendous achievements in prevention, diagnosis and treatment, infectious diseases remain a major concern in pediatrics. Additional efforts are urgently needed including judicious use of antibiotics to reduce resistance, development of modern vaccines and antibiotics and public health measures in order to overcome the battle against infections. This can be possible only with robust governmental support.

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel. screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryopre-cipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission. © 1995 Wiley-Liss, Inc.

Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients.A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE).Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak.B. cenocepacia is an emerging nosocomial pathogen among oncology patients.

Early-onset neonatal sepsis is a major cause of morbidity and mortality among newborn infants.To determine the incidence, type of pathogens and resistance to antibiotics among newborns with early-onset neonatal sepsis, and to identify the risk factors predisposing infants to resistant pathogens in order to reevaluate antibiotic regimens appropriate for resistant bacteria in these high risk neonates.We retrospectively studied maternal and neonatal variables of 73 term and near-term infants and 30 preterm infants, born over a period of 10.5 years and exhibiting early-onset neonatal sepsis (positive blood cultures in the first 72 hours of life).Predominant pathogens in term and near-term infants were gram-positive compared with gram-negative organisms (mostly Escherichia coli) in preterm infants. Mothers of infants with antibiotic-resistant organisms weremore likely to have prolonged rupture of membranes and prolonged hospitalization before delivery and to be treated with antibiotics. No trends towards more resistant strains of pathogens were recorded over the 10.5 years of the study period.Early-onset neonatal sepsis in term infants differs in bacterial species from that in preterm infants, with predominantly gram-positive organisms in term and near-term infants and gram-negative organisms in preterms. Rates of bacterial resistance to the combination of ampicillin and gentamicin, though higher among infants born to mothers with prolonged hospitalization who had been treated with antibiotics, still remained very low in our department. Thus, it seems that our classic antibiotic regimen is still appropriate for both term and preterm newborns.

OBJECTIVE. We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis. METHODS. This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m2 on day 1, followed by 50 mg/m2 per day (maximum: 70 mg/day), as primary or salvage monotherapy. Favorable response was defined as complete resolution of clinical findings and microbiologic (or radiographic/endoscopic) eradication (complete response) or significant improvement in these parameters (partial response). Efficacy was assessed at the end of caspofungin therapy in patients with a confirmed diagnosis who received ≥1 dose of caspofungin. The primary safety evaluation was the proportion of patients with clinical or laboratory drug-related adverse events. RESULTS. Of the 49 patients enrolled, 3 were CONCLUSIONS. Caspofungin was generally well tolerated in pediatric patients aged 6 months through 17 years. Efficacy outcomes in patients with invasive aspergillosis or invasive candidiasis were consistent with previous adult studies in these indications.

An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.

The aim of this study was to determine the in-vitro susceptibility of Streptococcus pneumoniae to levofloxacin, ciprofloxacin, sparfloxacin, ofloxacin, amoxycillin, cefepime and cefuroxime. In total, 105 isolates (clinical blood and sputum isolates from 1995–96) were selected from the collection of the Department of Clinical Microbiology of the Chaim Sheba Medical Centre. MICs were determined with an agar dilution method according to NCCLS guidelines. The MIC ranges with the test antibiotics against the pneumococcal isolates were: 0.5 mg/L, levofloxacin; 0.12–0.5 mg/L, sparfloxacin; 0.5–2 mg/L, ciprofloxacin; 0.5–1 mg/L, ofloxacin

Twenty eight children with herpes simplex encephalitis were followed up for a mean of 5.5 years. Two children died and 26survived, of whom 16 were left with no neurological sequelae and 10 had persistent neurological sequelae. Mean (SD) Glasgow coma score was significantly lower in the patients with neurological sequelae (7.7 (1.5)) and the patients who died (4.5 (0.7)), compared with the patients without neurological sequelae (11 (1.7)).

Hospital acquired infections including staphylococcal species are common in neonatal intensive care units. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was recently observed in our unit. The clinical and laboratory characteristics of all neonates with Staphylococcus aureus bacteremia during an 11-year period were retrospectively reviewed. Three groups of patients were compared: 1. Patients with CA-MRSA defined as MRSA-resistant only to beta-lactams, but sensitive to all other antibiotic groups and carried SCCmec IV. 2. Patients with multi-drug-resistant (MDR)-MRSA and 3. Patients with MSSA (methicillin-sensitive S. aureus). Forty-three neonates with documented S. aureus bacteremia were included. Of these 41 were preterm babies. Eleven infants had CA-MRSA, 20 had MDR-MRSA and 12 had MSSA bacteremia, the Panton-Valentine-Leukocidine gene (pvl-gene) was not present in any of these strains. Risk factors, clinical manifestations and laboratory tests were similar in all three groups studied. Although neonates infected with CA-MRSA were more premature and had more related diseases, the mortality rate was similar in all groups (9.1% in the CA-MRSA group). Skin infections, osteomyelitis or pneumatocele were not observed more frequently in the CA-MRSA group. We did not find significant differences in risk factors or outcomes in neonates in the three groups. One possible explanation for this observation is that the CA-MRSA outbreak strain did not contain the pvl-gene, which has been suggested to be a significant virulence factor.

Objective To report four cases of fixed drug eruption induced by hydroxyzine hydrochloride (Otarex, Teva, Israel). Case Summary Four children with restlessness who were treated with hydroxyzine hydrochloride developed fixed drug eruption of the penis. Drug discontinuation was followed by complete resolution of the skin eruption. Rechallenge resulted in the same drug rash. Macrophage migration inhibiting factor (MIF) assay with hydroxyzine hydrochloride was positive. Discussion The pathogenesis of fixed drug eruption and the role of macrophage MTF assay in diagnosis is discussed. Conclusions A fixed drug eruption induced by hydroxyzine hydrochloride is possible, but is a rare phenomenon.

Aim: The finding that 10% povidone-iodine skin disinfectant may compromise thyroid function in premature infants prompted its replacement with 0.5% chlorhexidine gluconate solution in 70% isopropanol. The objective of this study was to compare the incidence rates of true infection and contamination associated with the use of these two disinfectants in the neonatal intensive care unit. Methods: The study population comprised two cohorts of infants admitted to our neonatal intensive care unit: 1) in 1992–1993 when only 10% povidone-iodine was used as a skin disinfectant, and 2) in 1995–1996 when only 0.5% chlorhexidine gluconate solution in 70% isopropanol was used. A retrospective chart review was conducted to determine whether all documented positive blood, CSF and suprapubic aspirate cultures indicated true infection or contamination. True infection was defined as clinical symptoms and/or laboratory abnormalities suggestive of sepsis, with positive blood, CSF or suprapubic aspirate cultures. Results: 1146 infants were admitted during the study periods, 507 during the first period and 639 during the second. In the early group, 17.6% of infants had major malformations, 72.0% were premature and 25.2% had weights of >1500 g. Corresponding percentages for the latter group were 16.0%, 80.6% and 32.9%, respectively. No statistically significant differences were found between the two research periods in rate of infants with positive blood cultures, true infections, or contamination. Conclusion: The use of 0.5% chlorhexidine gluconate solution in 70% isopropanol as a skin disinfectant is justified in neonatal intensive care units because it is not associated with an increased incidence of infections as opposed to 10% povidone-iodine and is devoid of detrimental effects.

Summary Objectives. To retrospectively delineate predictors of adverse outcome by looking at the demographic features, therapy and outcome of systemic candida infection in a large tertiary care university-affiliated medical center. Methods. We reviewed the clinical data on 186 inpatients with candidemia over a 6year period. The major reason for their hospital admission was an underlying malignancy or an infection other than candidemia. Results. Candida albicans, tropicalis, parapsilosis, glabrata and krusei caused 54, 22, 13, 8 and 3% of the candidemia episodes, respectively. The overall mortality was 42% and it was highest in patients suffering from candidemia of the glabrata species (73%). Forty-eight (63%) of the 76 patients who received no anti-fungal treatment died compared to 38 (34%) of 110 patients who were treated ðP , 0:05Þ: Predictors of adverse outcome were intensive care unit stay, renal failure, thrombocytopenia and the need for mechanical ventilation or inotropic support. Conclusions. We identified four predictors of mortality from candidemia infection. Their validity should be further assessed and the specific candida strains and their susceptibility need to be methodically identified. Our data support immediate initiation of therapy at first identification of infection.

Tonsillitis is one of the most prevalent infections in children and adolescents. The etiologic agents might be viral or bacterial. About 30% of cases are reported to be of bacterial origin, mainly due to group A Streptococcus (GAS). Although in most instances GAS tonsillitis is a self-limited disease, antibiotic treatment is recommended, mainly to prevent the suppurative and nonsuppurative poststreptococcal sequelae of acute rheumatic fever and to prevent glomerulonephritis. In this paper we review the current knowledge of the etiology of acute and recurrent GAS tonsillitis, with special emphasis on a recent hypothesis regarding the etiology of bacterial eradication failure. While penicillin V remains the drug of choice for acute tonsillitis, other antibiotics are being approved and recommended for particular indications in both Europe and the United States.

Background: Erythema multiforme (EM) is a vesiculobullous disorder with variable manifestations which predominantly affects the skin. It is regarded as a hypersensitivity disorder which is triggered by multiple factors such as infection, drugs and food. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence as a pathogen in childhood. Patients: We describe two children in whom EM preceded VZV infection. In the first, a 5-year-old boy, EM was followed 3 days later by a classical disseminated varicella eruption. The diagnosis was reached by clinical, epidemiological and serological means. The second patient was a 13-year-old boy with EM which was followed 2 weeks later by Ramsay-Hunt syndrome. The diagnosis was confirmed by skin biopsy, positive serology and viral culture. Conclusion: The association of EM and VZV infection is probably more common than reported. In clinical cases of EM, VZV should be included in the list of possible causative agents.

Lipoteichoic acid (LTA) is thought to play a role in the interactions between Streptococcus pyogenes and host cells. We have examined the effect of exogenous LTA on the adherence and entry of S. pyogenes JRS4 strain into HEp-2 epithelial cells. LTA markedly inhibited bacterial entry in a concentration-dependent manner, up to 250 microg ml(-1). In contrast, LTA had only a slight inhibitory effect on adherence. LTA also inhibited the entry but not adherence of Salmonella typhimurium strain into HEp-2 cells. Binding experiments showed a dose-dependent binding of LTA to cells up to 10 microg ml(-1). Confocal laser microscopy imaging and analysis revealed that LTA was internalized by the epithelial cells and colocalized with F-actin. These results might imply that, following binding, exogenous LTA enters HEp-2 cells and exerts a cytotoxic effect that interferes with bacterial internalization. A possible target for LTA activity might be the actin cytoskeleton, which is known to be essential for bacterial uptake.

Acute epidural hematoma (AEH), a relatively common complication of head injury in children, persists in bearing high morbidity and mortality. Early establishment of prognosis could guide optimal patient allocation, and early identification of predictive signs could assist in choosing appropriate therapeutic interventions. This study aimed to delineate expeditiously obtainable prognostic markers for determining outcome in a subset of children with AEH. We reviewed our 11-year experience with 61 consecutive children +, Na+), hemoglobin and coagulation studies. Evaluation of the data collected on cause of injury, interval between trauma occurrence and presentation, clinical symptoms, Glasgow Coma Scale (GCS) scores, vital signs, laboratory test results, physical findings and surgical versus conservative management revealed that the best single predictors of outcome following AEH were the GCS and focal neurological deficits. Of all laboratory data obtained on admission, the blood potassium, pH and glucose test results correlated significantly with prognosis. Prognosis can be adequately and expeditiously estimated by selected markers within a comprehensive evaluation of children with AEH.

To determine the factors predisposing to Pseudomonas aeruginosa bacteremia as well as the prevalence, source of infection, outcome and prognostic factors in pediatric patients.Retrospective review of pediatric patients with P. aeruginosa bacteremia, at a large tertiary care hospital during a 6.5-year period.Seventy patients with P. aeruginosa bacteremia were identified. The annual rate of P. aeruginosa bacteremia remained unchanged during the study period. Antibiotic susceptibility remained unchanged except for two patients with extensive burns who developed resistant strains. Underlying diseases were malignancy (50%), prematurity (6%), burns (7%) and others (37%). The overall mortality associated with P. aeruginosa bacteremia was 20%. The fatality rate was higher among the young infants (compared with older children) and those who received previous antibiotic therapy (P = 0.02). Mortality rate was higher in nosocomial than in community-acquired infections (25% compared with 11.5%). The mortality rate of low birth weight and burns patients was significantly higher when compared with oncology patients or other patients, 75 and 40% compared with 11 and 19%, P = 0.01. Multiple regression analysis revealed a correlation only between the underlying disease and mortality (P = 0.02). In the oncology patients the only significant risk factor for mortality was absolute neutrophil countor =0.1 x 10(9)/l (P = 0.06).P. aeruginosa bacteremia, although apparently not increasing in incidence and antibiotic resistance, is still a common serious complication in immunocompromised children with a high mortality rate. We conclude that the underlying disease is the main determinant of the clinical outcome.

AmBisone (2.5–7 mg/kg/day as a continuous 1 h infusion) was evaluated prospectively from September 1994 to January 1998 in 24 very low birth weight infants (mean birth weight 847±244 g, mean gestational age 26 weeks) with systemic candidiasis. Mean age at onset of candidemia was 17 days. One patient had two episodes of candidiasis. Thirteen infants failed previous antifungal therapy with amphotericin B (with or without 5-flucytosine). Candida spp. were isolated from the blood in all 25 episodes and from skin abscesses and urine in four infants each, respectively. There were 13 isolates of Candida albicans, ten of Candida parapsilosis, two of Candida tropicalis and one of Candida glabrata. One infant had a mixed infection with C. albicans and C. parapsilosis. The mean duration of therapy was 21 days; the cumulative AmBisome dose was 94 mg/kg. Fungal eradication was achieved in 92% of the episodes; mean duration of AmBisome therapy until achieving eradication was 9 days. Twenty (83%) infants were considered clinically cured at the end of treatment. No major adverse effects were recorded; one infant developed increased bilirubin and hepatic transaminases levels during therapy. Four (17%) infants died; in two of them (8%) the cause of death was directly attributed to systemic candidiasis. Conclusion: AmBisome represents an effective, safe and convenient antifungal agent in the therapy of systemic fungal infections in very low birth weight infants.

Differences in the course of invasive meningococcal disease, in prevalence, case-to-carrier ratio, geographical pattern, age distribution and antibiotic resistance have been related to major serogroups and their serotypes. The relationship between Neisseria meningitidis serogroups and clinical manifestation, outcome and patient characteristics are assessed. All hospitalized patients in six major hospitals in central Isral with a verified meningococcal disease during 1990–1994 were included (n = 66). Their personal and clinical data and the results of bacteriological and serological tests of their blood and cerebrospinal fluid (CSF) were recorded. Meningococci were isolated from both blood and CSF, from blood alone, and from CSF alone in 60.6%, 18.2% and 21.2% of the cases, respectively. The highest proportion of isolations were from infants < 1 year (34.8%), followed by children aged 1 to 5 years (25.8%). Serogroup B prevailed in 62.1%, while group C and W135 accounted for 28.8% and 9.1%, respectively. Serogroup B predominated in children < 1 year, while in patients aged 5–22 years, C strains were the major pathogen (P < 0.001). Serogroup B accounted for 93% of the cases of meningitis, 58% of meningococcemia and 42% of fulminant meningococcemina, while group C strains were the major cause of fulminant meningococcemia (50%). The overall case fatality rate was 7.6%: fulminant meningococcemia 8.3%, and meningococcemia 10%. It was concluded that N. meningitidis group C continues to account for almost a third of the cases of meningococcal disease and is the major cause of fulminant meningococcemia.

AIM The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres ⩾ 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres ⩾ 1:8 than routinely vaccinated preterm infants (p

The cases are presented of four haemophiliacs infected with human immunodeficiency virus (HIV) and with septic arthritis among the 340 patients followed at our centre. The data of these cases and 39 additional HIV-infected haemophiliacs with septic arthritis, identified in a literature search, are reviewed. The spectrum of bacterial pathogens is limited and somewhat different from that in other risk groups. The localization is exclusively to joints affected by haemophilic arthropathy. The laboratory picture is characterized by the absence of peripheral leucocytosis, varying CD4-helper cell counts, a high erythrocyte sedimentation rate and fever. The clinical picture mimics that of haemarthrosis, often causing a delay in diagnosis. Treatment with systemic antibiotics is often sufficient, obviating the need for arthrotomy and open drainage. Prognosis related to the joint function is relatively good, but poor when related to the medium- to long-term survival of the patient.

Acute transverse myelopathy is an uncommon disease that manifests with gradually developing weakness of the lower extremities associated with bladder or bowel dysfunction, sensory deficits, and pain localized in the back, legs, or abdomen. There are controversies in the literature regarding the role of steroids in the treatment of acute transverse myelopathy. Recently, a pilot open study of five children with acute transverse myelopathy treated with high-dose methylprednisolone demonstrated significant shortening of motor recovery when compared with an historic control group receiving either no treatment or low-dose steroids. The authors add their experience of 10 children with acute transverse myelopathy treated with high-dose methylprednisolone as soon as the diagnosis was confirmed. The median time of motor recovery in the present series was 5.5 compared with 23 days in the other study. No significant side effects were observed after treatment. This study provides further support that this treatment modality is safe and efficient and should be suggested for all children with acute transverse myelopathy after establishing the diagnosis.

Mycobacterium simiae is rarely isolated in clinical settings of non-HIV-infected patients. Isolation of M. simiae from clinical specimens in clusters has been limited to some parts of the world that include Israel, Cuba and the southern USA, mainly Texas. Only 8 patients with HIV and disseminated M. simiae infection have been previously described in the English literature. Successful treatment of disseminated M. simiae infection has never been reported and 6 of the cases have died within 8 months of diagnosis. We reviewed retrospectively the medical records of HIV-infected patients who had positive blood or bone marrow cultures for M. simiae at the Sheba Medical Center, Tel-Hashomer, Israel, between January 1992 and December 1996. A case of disseminated M. simiae infection was defined as isolation of M. simiae in blood or bone marrow culture in an HIV-infected patient with a compatible, otherwise unexplained, systemic disease. Mycobacterium simiae was isolated in blood and/or bone marrow cultures from 3 HIV-infected patients during the last 5 y. We describe the first successful treatment in AIDS patients with disseminated M. simiae infection. The patients are alive and well 20 months after instituting a combination of 3 antimycobacterial agents, clarithromycin, ethambutol and ciprofloxacin and intensive antiretroviral therapy.

A report on a 15-year-old male with a diagnosis of poliomyelitis-like syndrome (Hopkins’ syndrome) following an asthmatic attack is presented. The prognosis of Hopkins’ syndrome is usually poor and the patients remain with permanent paralysis of the affected limb. The outcome correlates with severity of the initial injury to the anterior horn cell as reflected by abnormal electrophysiologic studies. This is the first case report of treatment with i. v. gamma globulin in Hopkins’ syndrome which resulted in a nearly complete recovery.