Dynamics of childhood invasive meningococcal disease in Israel during a 22-year period (1989-2010).

AIM: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). METHODS: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. RESULTS: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). CONCLUSIONS: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.

Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. AIM: This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). METHODS: In this retrospective case-control study, all cases of K. pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. FINDINGS: Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. CONCLUSIONS: Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance.

Distribution of fluconazole-resistant Candida bloodstream isolates among hospitals and inpatient services in Israel.

The emergence of fluconazole-resistant Candida (FRC) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. We prospectively analysed Candida bloodstream isolates in 18 medical centres in Israel (six tertiary-care and 12 community hospitals). The study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). Institutional FRC bloodstream infection rates correlated with annual inpatient days, and were strongly associated with the presence and activity of haematology/oncology services. Infection with Candida krusei and fluconazole-resistant Candida glabrata occurred exclusively in hospitals with >600 beds. These findings suggest that empirical antifungal strategies should be tailored to the nosocomial setting.

Epidemiology and clinical significance of non-tuberculous mycobacteria isolated from pulmonary specimens.

SETTING: A tertiary university medical centre in northern Israel. OBJECTIVE: To evaluate the clinical significance of non-tuberculous mycobacteria (NTM) isolated from pulmonary specimens. DESIGN: Clinical and microbiological data were collected from patient files. Cases were classified as definite, probable and possible NTM. RESULTS: Between 2004 and 2010, 215 cases with respiratory isolates of NTM were identified. Mycobacterium xenopi was the most common species (n = 84, 39.1%), followed by M. simiae (n = 52, 24.2%). A total of 170 (79.1%) cases were classified as possible and 24 (11.2%) as probable NTM. Only 21 (9.8%) cases were considered definite NTM, the majority of which were M. kansasii and M. avium complex. CONCLUSIONS: M. xenopi and M. simiae are the most prevalent species of NTM isolated from respiratory samples in northern Israel. However, most of these isolates represent colonisation. Of the relatively small number of clinically significant isolates, M. kansasii and M. avium complex were the most common.

What is the clinical relevance of respiratory syncytial virus bronchiolitis?: findings from a multi-center, prospective study.

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children <24 months of age who presented with <4 days duration of AB. Subjects were divided into the following groups: "only RSV," "also RSV," "no RSV," and "no pathogen." The clinical severity score on admission as well as the overall severity of disease was assessed. RSV was the most common cause of AB (77.5 %). "Only RSV" or "also RSV" patients had a higher clinical score on admission compared to those with "no RSV," p < 0.001 and p < 0.02, respectively. "Only RSV" and "also RSV" patients had a higher disease severity score when compared to patients with "no RSV," 5.9 ± 1.4 vs. 5.1 ± 1.5, p < 0.001, and 5.6 ± 1.4 vs. 5.1 ± 1.5, p < 0.02, respectively. Disease severity did not vary as a function of transfer to the pediatric intensive care unit (PICU) or duration of supplemental oxygen, yet, "only RSV" was associated with a longer length of stay (LOS) than "no RSV," p < 0.02. "Only RSV"-related AB was associated with a more severe initial clinical presentation and a longer LOS. There appears to be little immediate clinical benefit to diagnosing RSV AB to the individual patient, but the application of these diagnostic methods may have significant cost-saving implications and, thus, deserves consideration by medical professionals and health policy analysts.

Brain abscess in children - epidemiology, predisposing factors and management in the modern medicine era.

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 27 children (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.

Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads.

Adult mesenchymal stem cells (MSC) that are able to differentiate into various mesenchymal cell types are typically isolated from bone marrow, but their significant presence in human peripheral blood (PB) is controversial. Fibrin microbeads (FMB) that bind matrix-dependent cells were used to isolate MSC from the mononuclear fraction of mobilized PB of adult healthy human donors treated with a granulocyte colony-stimulating factor. Isolation by plastic adherence resulted in a negligible number of MSC in all samples tested, whereas FMB-based isolation yielded spindle-shaped cell samples that could further expand on plastic or on FMB in eight out of the 11 samples. The yield of these cells at days 17-18 after the harvest was approximately 0.5% of the initial cell number. The isolated cells were grown on plastic and characterized by FACS analysis and immunohistochemistry for specific markers. Following culturing and first passage, the FMB-isolated cells stained positive for mesenchymal stromal cell markers CD90 and CD105, expressed vimentin and fibronectin and were negative for hematopoietic markers CD45 and CD34. These cells could differentiate into osteoblasts, adipocytes and chondrocytes. This study indicates that FMB may have special advantage in isolating MSC from sources such as mobilized PB, where the number of such cells is scarce.

An outbreak of Q fever in an urban area in Israel.

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.

Clinical and epidemiologic significance of coagulase-negative staphylococci bacteremia in a tertiary care university Israeli hospital.

OBJECTIVES: To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia. DESIGN: Prospective cohort study. SETTING: A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997. RESULTS: 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%. CONCLUSION: Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

Staphylococcal scalded-skin syndrome in a very low birth weight premature infant.

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-positive Staphylococcus 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.

Review of 49 neonates with acquired fungal sepsis: further characterization.

BACKGROUND: Neonatal acquired fungal sepsis (AFS) is a risky condition that warrants every effort for early diagnosis and management. METHODS: We retrospectively reviewed the medical charts of all 4445 neonatal intensive care unit (NICU) admissions in the past 10 years and detected 49 neonates with AFS. We then compared their data with those of 49 matched control neonates who did not have AFS. The following details were collected: gestational, perinatal and neonatal courses; bacterial sepsis; antibacterial therapy; laboratory and imaging investigations; and antifungal therapy and its complications. RESULTS: The incidence of AFS was.4 to 2 cases per 1000 live-births and 3.8% to 12.9% of very low birth weight (VLBW) infants. Compared with 1989 through 1992, between 1993 and 1995 the rate of AFS in VLBW neonates significantly increased (3. 8%-5.6% --> 9.6%-12.9%), along with a significant increase of NICU admission rate (369-410 --> 496-510 admissions/year). Compared with controls, AFS neonates had significantly longer hospitalizations, higher rates of mechanical ventilation, umbilical vein catheterization, and previous treatment with broad-spectrum antibacterial agents (amikacin, vancomycin, ceftazidime, or imipenem). At the onset of AFS, 42.8% of patients had hyperthermia and 40.9% had normal white blood cell count. Causative fungi were as follows: Candida albicans-42.8% of cases, Candida parapsilosis-26.5%, and Candida tropicalis-20.4%. Fungal dissemination was rare, complications of antifungal therapy were infrequent, and no deaths occurred. CONCLUSIONS: First, non-albicans Candida have become more frequent in neonatal AFS. Second, mechanical ventilation and antibacterial agents are significant risk factors for AFS. Third, hyperthermia is a frequent presenting sign of AFS. Fourth, a normal white blood cell count does not rule out AFS. Fifth, meningeal involvement in neonatal AFS should be ruled out before initiation of antifungal therapy. Sixth, the policy of empiric antifungal therapy for AFS should be considered on an individual NICU basis.newborn infant, fungal sepsis, clinical signs, risk factors.

Device-associated, device-day infection rates in an Israeli adult general intensive care unit.

Surveillance is an essential element of hospital infection control programs. Previous studies have shown that interhospital comparison of intensive care unit (ICU) nosocomial infections (NI) may be best made by comparing ICU-type-specific, device-associated infection rates and that these adjusted rates vary by ICU type. The aim of this study was to evaluate whether significant structural improvements introduced in an adult general ICU were associated with changes in the NI rates in this unit. In addition, we compared these rates with those of ICUs reported by the National Nosocomial Infections Surveillance (NNIS) System of the Centers for Diseases Control and Prevention. During a 12-month period 337 patients were surveyed. There were 20 ventilator-associated pneumonias (VAP)/1000 ventilator (VEN)-days, 12 bloodstream infections (BSI)/1000 central vascular catheter (CVC)-days and 14 urinary tract infection (UTI)/1000 indwelling urinary catheter (IUC)-days. Structural changes and reduction in device utilization ratios were not followed by change in NI rates in this unit. VAP and BSI rates were comparable to those reported for neurosurgical and burn ICUs, respectively, in the NNIS System, despite a much higher device utilization ratios. The present study provides specific surveillance data for further interhospital comparison with similar types of ICUs.

Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group.

An ongoing nationwide prospective surveillance program for invasive H. influenzae b (Hib) disease in Israel enabled us to study the effectiveness of a national infant Hib immunization program, which included all infants born since January 1994. The vaccine used was Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis b (PRP-OMPC). For the cohort born during the 3 years since January 1994, the vaccine effectiveness was 94.9% for all invasive Hib diseases and 96.6% for meningitis. The efficacy in fully immunized subjects was 98.7 and 99.5%, respectively. A herd immunity effect could be observed, since a reduction in cases also occurred among infants too young to be immunized. No increase in invasive cases caused by S. pneumoniae and N. meningitidis was observed during the study period. This is the first report outside North America and Western Europe that demonstrates a nationwide extensive reduction of invasive Hib disease within a short time of the introduction of Hib conjugate vaccines to the infant immunization program.

Partitioning of dioxins, dibenzofurans, and coplanar PCBS in blood, milk, adipose tissue, placenta and cord blood from five American women.

Partitioning of dioxins, dibenzofurans and the dioxin-like coplanar PCBs was determined by congener-specific high resolution gc-ms analysis of compounds in 6 tissue samples each from 5 women. Samples were whole blood obtained prior to delivery; maternal adipose tissue, cord blood and placenta obtained during cesarean section delivery; and whole blood and milk taken at the time of first obstetrical follow-up examination, one to two months following delivery. All women lived in upstate New York. Specimens were collected in late 1995 and early 1996. Mean measured levels of total PCDDs, PCDFs and coplanar PCBs were 352 pg/g for adipose tissue, 526 pg/g for predelivery blood, 182 pg/g for placenta, 165 pg/g for cord blood, 352 pg/g for postpartum blood and 220 pg/g for milk. Mean total TEQ levels were 11.6 pg/g TEQ for adipose tissue, 12.1 pg/g TEQ for predelivery blood, 10.5 pg/g TEQ for placenta, 5.8 pg/g TEQ for cord blood, 10.0 pg/g TEQ for postpartum blood and 10.2 pg/g TEQ for milk.

Early emergence of ganciclovir-resistant human cytomegalovirus strains in children with primary combined immunodeficiency.

Children with primary combined immunodeficiency (CID) and human cytomegalovirus (HCMV) infection often deteriorate despite antiviral therapy. In this study, the emergence of ganciclovir-resistant strains was examined in 6 children with CID and HCMV infection, using sequence analysis of the HCMV UL97 gene and virus susceptibility assays. Mutations in the proposed ATP binding site associated with ganciclovir resistance were found in 4 of the 6 children. In 1 patient with B severe CID, an unusual multiplicity of mutations was found in the UL97 substrate binding domain between aa 590-606. All mutations were detected within 10 days to 3 weeks from initiation of therapy. The emergence of resistant strains in children with CID appears earlier than in other groups of HCMV-infected patients. These findings may have relevance to the cellular pathways involved in viral DNA repair and mutagenesis, and they indicate the need for early and frequent genotypic monitoring and prompt therapeutic modification in this patient population.