Itzhak Levy

Chlorhexidine-impregnated dressing for prevention of colonization of central venous catheters in infants and children: a randomized controlled study.

Background: Infections of short term, nontunneled, intravascular catheters are often caused by migration of organisms from the insertion site. The aim of this study was to evaluate the effectiveness and safety of a chlorhexidine gluconate-impregnated dressing for the reduction of central venous catheter (CVC) colonization and CVC-associated bloodstream infections in infants and children after cardiac surgery. Methods: This prospective, randomized, controlled study was conducted in the pediatric cardiac intensive care unit of a tertiary care pediatric medical center. Patients 0–18 years of age who were admitted to the pediatric cardiac intensive care unit during a 14-month period and required a CVC for >48 hours were randomized to receive a transparent polyurethane insertion site dressing (control group) or a chlorhexidine gluconate-impregnated sponge (Biopatch) dressing covered by a transparent polyurethane dressing (study group). The main outcome measures were rates of bacterial colonization, rates of CVC-associated bloodstream infections and adverse events. Results: Seventy-one patients were randomized to the control group and 74 to the study group. There were no significant between group differences in age, sex, Pediatric Risk of Mortality score or cardiac severity score. CVC colonization occurred in 21 control patients (29%) and 11 (14.8%) study patients (P = 0.0446; relative risk, 0.6166; 95% confidence interval, 0.3716–1.023). Bloodstream infection occurred in 3 patients (4.2%) in the control group and 4 patients (5.4%) in the study group. Local redness was noted in 1 control patient and 4 study group patients. Conclusions: The chlorhexidine gluconate-impregnated sponge is safe and significantly reduces the rates of CVC colonization in infants and children after cardiac surgery.

Outcome of early-onset sepsis in a national cohort of very low birth weight infants.

BACKGROUND: Early-onset sepsis (EOS) is associated with significant morbidity and mortality among infants with a very low birth weight (VLBW); however, there is a sparse amount of complete data on large cohorts. OBJECTIVE: To evaluate the mortality and major morbidities among VLBW infants with EOS. METHODS: This was a population-based observational study. Data were prospectively collected by the Israel Neonatal Network on all VLBW infants born in Israel from 1995 through 2005. Univariate and multivariable analyses were performed to assess the independent association of EOS on morbidity and mortality of VLBW infants. RESULTS: The study cohort included 15 839 infants, of whom 383 (2.4%) developed EOS. EOS was associated with significantly increased odds for mortality (odds ratio [OR]: 2.57 [95% confidence interval (CI): 1.97–3.35]), severe intraventricular hemorrhage (OR: 2.24 [95% CI: 1.67–3.00]), severe retinopathy of prematurity (OR: 2.04 [95% CI: 1.32–3.16]), and bronchopulmonary dysplasia (OR: 1.74 [95% CI: 1.24–2.43]). EOS was associated with an increased risk of death and/or severe neurologic morbidity (OR: 2.92 [95% CI: 2.27–3.80]). CONCLUSIONS: Although only 2.4% of VLBW infants had an episode of EOS, these infants were at an approximately threefold excess risk of death or major neurologic morbidities.

Diagnostic Accuracy of PCR Alone Compared to Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis: a Systematic Review

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

Invasive fungal infections in pediatric oncology

Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population.

Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants.

OBJECTIVE The purpose of this study was to determine the incidence, causative pathogens, and risk factors for early onset sepsis (EOS) among very-low-birthweight (VLBW) infants. STUDY DESIGN This was a population based observational study. Data were prospectively collected by the Israel Neonatal Network between 1995 and 2005. Multivariable analyses identified independent risk factors for EOS. RESULTS EOS developed in 383 of 15,839 infants (2.42%). Fifty-five percent of pathogens isolated were gram-negative bacteria. Lack of prenatal care (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.32-2.86), delivery room resuscitation (OR, 2.49; 95% CI, 1.91-3.24), membrane rupture > 24 hours without amnionitis (OR, 2.10; 95% CI, 1.53-2.88), amnionitis with membrane rupture < 24 hours (OR, 4.28; 95% CI, 2.97-6.16), and amnionitis with membrane rupture >or= 24 hours (OR, 8.15; 95% CI, 5.98-11.10) were associated with EOS, but not antenatal steroids or gestational age. CONCLUSION EOS was caused mainly by gram-negative bacteria. Prolonged rupture of membranes and amnionitis have an additive effect on EOS with an above 8-fold excess risk when both were present.

Infectious complications of peripherally inserted central venous catheters in children.

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

Exserohilum: an emerging human pathogen

Exserohilum is a dematiaceous fungus that may cause a spectrum of diseases in humans, including skin and corneal infection, invasive disease, and allergic fungal sinusitis. The aim of this work is to describe two new cases of Exserohilum infection and to review the literature. The review yielded 33 cases of Exserohilum infection, of which 23 were reported since 1993. Most occurred in regions with hot climates, such as India, Israel, and the southern USA. Impaired immunity was present in the majority of patients with invasive and skin infections, whereas local trauma and atopy were the predisposing factors in those with corneal infections and allergic fungal sinusitis, respectively. Surgical debridement was the principal mode of therapy for allergic fungal sinusitis. Amphotericin B was the initial single antifungal agent used in all cases of invasive disease; the response rate was low but improved with the addition of triazole agents. Outcome appeared to be better than for other mold infections and depended mainly on the underlying diseases.

A prospective study of Gram-negative bacteremia in children.

BACKGROUND Hospital- and community-acquired Gram-negative bacteremia is a significant cause of mortality and morbidity in pediatric medical centers. Gram-negative organisms are isolated in > 50% of pediatric patients with bacteremia. OBJECTIVES To analyze clinical and epidemiologic variables associated with Gram-negative bacteremia in a tertiary childrens medical center. METHODS A 6-year prospective study of children with Gram-negative bacteremia in a tertiary care childrens medical center in Israel. RESULTS Three hundred seventy-four episodes of Gram-negative bacteremia were studied during 6 years. The predominant isolates were Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli, which accounted for 109, 81 and 79 episodes (26, 20 and 19%), respectively. Of all episodes 43% occurred in neonates and infants younger than 2 years and 47% were hospital-acquired. Underlying conditions mainly acute leukemia and lymphoma, were present in 55% of the patients. Urinary tract infection followed by lower respiratory tract infection were the most common identified sources of bacteremia. Central intravenous catheters were associated with 53% of the episodes. The crude mortality was 11.4%. Increased mortality was significantly associated with acute leukemia, neutropenia, hospital-acquired infections and previous corticosteroid therapy (P = 0.03, 0.003, 0.006 and 0.01, respectively). Increased antibiotic resistance of hospital-acquired vs community-acquired isolates was noted; 44 to 77% resistance of nosocomial Klebsiella and Enterobacter sp. to second and third generation cephalosporins and 18% were resistant to amikacin. CONCLUSIONS Klebsiella pneumoniae is currently the most common organism causing Gram-negative bacteremia in children. Because of the relatively high resistance of Gram-negative organisms to second and third generation cephalosporins, we suggest that empiric antibiotic therapy for Gram-negative bacteremia include a combination of an aminoglycoside and an anti-Pseudomonas beta-lactam.

Candida endocarditis in neonates: report of five cases and review of the literature

Candidal endocarditis is an uncommon and serious complication of invasive Candida infection in neonates. The aim of this study was to further characterise candidal endocarditis in neonates. Between 1995 and 2000, 56 patients were diagnosed with Candida bloodstream infections (CBSI) in the Neonatal Intensive Care Unit of Schneider Childrens Medical Center of Israel. Five of them (9%) developed mycetoma of the right atrium. None of the patients had congenital heart disease or a central venous catheter in the right heart at the time of diagnosis. All were treated with amphotericin B alone or in combination with other antifungals, without surgical intervention. One patient died of the disease and one died later of polymicrobial sepsis and necrotizing enterocolitis. A review of the literature since 1980 yielded an additional 25 cases of candidal endocarditis. For the whole sample (n = 30) survival rate was 73.1%. Six of the 10 patients treated with antifungal agents and surgery survived (60%), compared with 13 of the 20 patients treated only medically (65%) (P = 1.0). Candida endocarditis in neonates differs from fungal endocarditis in adults in risk factors, clinical presentation and outcome. As the outcome of surgical and medical treatment are comparable, antifungal therapy alone may be a valid therapeutic option in high‐risk cases.

Is lenticulostriated vasculopathy a sign of central nervous system insult in infants with congenital CMV infection

Background In previous studies, lenticulostriated vasculopathy (LSV) was detected in 0.4–5.8% of neonates who had undergone brain ultrasound studies during the neonatal period. Most infants were referred from neonatal intensive care units. Various clinical conditions were associated with LSV including intrauterine infections. Objective To investigate whether LSV as a single abnormal finding in neonates with congenital cytomegalovirus (CMV) infection is a sign of central nervous system (CNS) involvement. Methods Ultrasonographic and clinical data of all infants with congenital CMV infection, followed in our hospital, were collected. All infants with symptomatic congenital CMV infection and CNS involvement were treated with ganciclovir for 6 weeks, followed by valganciclovir until the age of 1 year. Infants with asymptomatic as well as symptomatic infections were followed up with brainstem evoked response and behavioural studies every 4 months until 4 years of age. Results 92 infants diagnosed with congenital CMV infection were included in the study. In 50 (54.3%) infants, LSV was detected on initial brain ultrasound. Among these patients, 21 (42%) infants had other ultrasonographic findings consistent with congenital CMV infection; 11 (22%) had other symptoms of CNS involvement and in 18 (36%) cases the only abnormal finding was LSV. In 9 of the 18 infants with LSV as the only finding on initial examination, antiviral therapy was not started. Hearing deterioration developed in all nine infants between ages 4 and 34 months. Subsequent to these cases, the authors modified their therapy protocol and began treating congenital CMV infants with only LSV. 9 infants were treated and all maintained normal hearing after 8–27 months of follow-up (p<0.01). Conclusions LSV is a common finding in infants with symptomatic congenital CMV infection and is a sign of CNS involvement. Moreover, LSV is a possible marker of high risk for sensorineural hearing loss in infants with congenital CMV infection.