Publications by authors named "Itzhak Levy"

65 Publications

Peripheral Venous Catheter-related Bloodstream Infections in Hospitalized Children: The Role of Gram-negative Bacteria.

Pediatr Infect Dis J 2021 Jul 6. Epub 2021 Jul 6.

From the Department of Pediatrics A, Schneider Children's Medical Center, Petah Tikva, Israel Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Infectious Diseases Unit Department of Pediatrics B Department of Pediatrics C Pediatric Heart Institute, Schneider Children's Medical Center, Petah Tikva, Israel Microbiology Laboratory, Rabin Medical Center, Petah Tikva, Israel.

Background: Peripheral venous catheter (PVC) is the most used vascular access device in medicine, allowing administration of intravenous fluids and medications. Known complications associated with PVC include extravasation, phlebitis and rarely bloodstream infection (BSI). Data regarding PVC-related BSI in children are lacking. Our aim was to evaluate the epidemiology, clinical and microbiologic characteristics of pediatric inpatients with PVC-related BSI.

Methods: A retrospective study was conducted in a pediatric tertiary care center. Children with BSI, admitted to general pediatric departments during 2010-2019, were identified and their medical records examined. Patients with BSI and phlebitis were further characterized and included in the analysis. We excluded patients with central venous catheters, other identified source of infection and with BSI upon admission. Data collected included patients' demographics and clinical and microbiologic characteristics.

Results: Twenty-seven children with PVC-related BSI were identified and included in the study, consisting of 0.2% of the total BSI cases. Patient's median age was 24 (range, 1.5-213) months, 14/27 (52%) were female and 6 (22%) were previously healthy while 21 (78%) had prior medical conditions. Sixteen (59.3%) patients had Gram-negative BSI and 6 (22.2%) Gram-positive bacteria. Polymicrobial infection occurred in 4 (14.8%) patients and Candida albicans in 1 (3.7%) patient. The most common isolated bacteria were Klebsiella spp and Staphylococcus aureus. Longer dwell-time was a predictor of Gram-negative bacteria.

Conclusions: PVC-related BSI due to Gram-negative bacteria was more common than to Gram-positive bacteria. Clinicians should consider an initial broad-spectrum antibiotic coverage for PVC-related BSI in hospitalized pediatric patients.
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July 2021

Disseminated Mucormycosis in Immunocompromised Children: Are New Antifungal Agents Making a Difference? A Multicenter Retrospective Study.

J Fungi (Basel) 2021 Feb 25;7(3). Epub 2021 Feb 25.

The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva 4920235, Israel.

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The aim of this study was to assess the contemporary management strategies and outcomes of disseminated mucormycosis in the pediatric population.

Methods: We conducted a retrospective search in six large tertiary medical centers for all cases of disseminated mucormycosis that occurred between 2009-2020 in patients aged 1-20 years.

Results: Twelve cases were identified. Underlying conditions included hematological malignancies ( = 10), solid tumor (post-autologous hematopoietic stem cell transplantations; = 1), and solid organ (liver) transplantation ( = 1). In all cases, amphotericin B formulations were administered as first-line therapy; in eight cases, they were also administered in combination with an echinocandin or triazole. Seven patients underwent surgical debridement procedures. The six-week mortality was 58%. Among the patients diagnosed between 2009-2015, one of the six survived, and of those diagnosed between 2016-2020, four of the six were salvaged.

Conclusions: Disseminated mucormycosis is a life-threatening and often fatal disease, and improved diagnostic and therapeutic strategies are needed. Nevertheless, in this population-based study, five patients (42%) were salvaged through combined liposomal amphotericin/triazole treatment and extensive surgical interventions.
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February 2021

Clinical Features and Comparison of Kingella and Non-Kingella Endocarditis in Children, Israel.

Emerg Infect Dis 2021 03;27(3):703-709

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.
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March 2021

Factors predicting efficacy of ethanol lock therapy as catheter salvage strategy for pediatric catheter-related infections.

Pediatr Blood Cancer 2021 May 22;68(5):e28856. Epub 2020 Dec 22.

Pediatric Infectious Diseases Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: Catheter-related infections are difficult to cure, and failure rates are high. We aimed to evaluate the efficacy and safety of ethanol lock therapy (ELT) as catheter salvage strategy in children with central-line-associated bloodstream infection (CLABSI), and to identify factors associated with treatment failure.

Methods: Data were collected of all the children who received ELT for treatment of CLABSI during 2013-2018 due to failure of standard therapy or multiple catheter-related infections. Univariate and multivariate analyses of risk-factors for ELT failure were performed. Catheter salvage rates were compared to those achieved using systemic antimicrobials alone in an historical control group.

Results: A total of 123 ELT episodes among 95 patients were analyzed. The majority of patients had underlying hemato-oncological disorders. Approximately half the episodes occurred in patients with implantable ports. Early and late treatment failure rates of ELT were 16% (20/123) and 7% (9/123), respectively. Overall, successful catheter salvage was achieved in 78% (96/123) of episodes, compared to 54% using systemic antimicrobials alone (P < .001), including mycobacterium, candida, and most staphylococcus aureus infections. Adverse events were reported in 9% (11/123) of episodes and were mostly mechanical. Multivariate analysis identified four risk factors for ELT failure: Gram-positive bacteria, elevated C-reactive protein, signs of tunnel infection, and low absolute neutrophil counts.

Conclusions: Our findings support the use of ELT for catheter salvage in children with CLABSI who failed standard therapy or had multiple catheter-related infections. The identified variables associated with ELT failure may help identify patients who can most benefit from ELT.
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May 2021

Frequency of Multifocal Disease and Pyogenic Arthritis of the Hip in Infants with Osteoarticular Infection in Three Neonatal Intensive Care Units.

J Pediatr 2020 12 22;227:157-162. Epub 2020 Jul 22.

St. Christopher's Hospital for Children and Drexel University College of Medicine, Philadelphia, PA.

Objective: To describe the clinical features of osteoarticular infection in infants cared for in neonatal intensive care units (NICUs) and to assess the presence of multifocal infection.

Study Design: Retrospective medical record review with structured data abstraction of infants with osteomyelitis or pyogenic arthritis or both in NICUs at 3 children's hospitals over a 29-year period.

Results: Of the 45 cases identified, 87% occurred in prematurely born infants, with a median gestational age of 27.4 weeks (IQR, 26, 31 weeks). Median postnatal age at diagnosis of infection was 33 days (IQR, 20, 50 days). Osteomyelitis was present without joint involvement in 53% and with joint involvement in 44% of cases. Methicillin-susceptible Staphylococcus aureus (71%) was the predominant pathogen, despite prevalent methicillin-resistant S aureus in community-associated infections. More than 1 bone was infected in 34% of cases. The femur (in 50% of patients) was the most frequently involved bone and the hip (in 20% of patients) was the most frequently involved joint. Bacteremia persisted for 4 or more days in 54% of patients with a positive blood culture despite active antimicrobial therapy.

Conclusions: Among infants with osteoarticular infection in NICUs, multifocal disease is common and frequently is unsuspected. Search for additional sites of infection including the hip is warranted following the diagnosis of osteoarticular infection at a single site. Involvement of contiguous joints should be suspected in cases of osteomyelitis; conversely the presence of pyogenic arthritis usually indicates extant osteomyelitis in a contiguous bone.
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December 2020

Isavuconazole As Successful Salvage Therapy for Mucormycosis in Pediatric Patients.

Pediatr Infect Dis J 2020 08;39(8):718-724

From the Day Hospitalization Department, Infectious Diseases Unit, Hemato-Oncology Department, Intensive Care Unit, Schneider Children's Medical Center of Israel, Petah Tikva.

Background: Mucormycosis is a rare but emerging life-threatening fungal disease with limited treatment options. Isavuconazole is a new triazole that has shown efficacy in adults for primary and salvage treatment of mucormycosis. However, data in children are scarce.

Methods: The demographic and clinical data of pediatric patients with proven mucormycosis who were treated with isavuconazole in 2015 to 2019 at 2 centers were collected.

Results: Four children of median age 10.5 years (range 7-14) met the study criteria. Three had underlying hematologic malignancies, and 1 had sustained major trauma. Isavuconazole was used as salvage therapy in all: in 3 patients for refractory disease, and in 1 after intolerance to another antifungal drug. Isavuconazole was administered alone or combined with other antifungal agents. Following treatment and surgical intervention, complete clinical, radiologic and mycologic responses were documented in all patients. A literature review identified 8 children with mucormycosis who were successfully treated with isavuconazole, as salvage therapy in the majority.

Conclusion: Our limited experience supports the use of isavuconazole as salvage therapy in pediatric mucormycosis.
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August 2020

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia.

Br J Haematol 2020 04 29;189(2):339-350. Epub 2019 Dec 29.

The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva, Israel.

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004-2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51-9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24-9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47-60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01-40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.
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April 2020

Q Fever and Kingella kingae Endocarditis in a Toddler: A Rare Coinfection Case.

Pediatr Infect Dis J 2019 12;38(12):e336-e337

From the Department of Pediatrics B.

A toddler after tetralogy of Fallot graft repair in infancy was diagnosed with endocarditis. Blood cultures were positive for Kingella kingae and serology was positive Coxiella burnetii. He was treated medically and surgically. A postoperative specimen polymerase chain reaction confirmed a coinfection. A comprehensive patient history was imperative for identification of an unlikely infection at this age.
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December 2019

Vacuum-Assisted Closure for the Treatment of Deep Sternal Wound Infection After Pediatric Cardiac Surgery.

Pediatr Crit Care Med 2020 02;21(2):150-155

Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Objectives: Vacuum-assisted closure is being increasingly used to treat deep sternal wound infection following cardiac surgery, but most of the data refer to adults. This study investigated the safety and efficacy of vacuum-assisted closure in pediatric patients.

Design: Retrospective file review.

Setting: Tertiary pediatric medical center.

Patients: All children with deep sternal wound infection treated with vacuum-assisted closure in 2003-2016.

Interventions: Epidemiological, clinical, and microbiological data were collected from the medical records.

Measurements And Main Results: The cohort included 50 patients (0.9% of cardiac patients operated during the study period) of median age 6.5 months (interquartile range, 2-12.75 mo; range, 1 wk to 14 yr) and median weight 5.1 kg (interquartile range, 4-9.75 kg). The most frequent heart defects were tetralogy of Fallot (22%) and ventricular septal defect (20%); 38% of patients had cyanotic heart disease. Deep sternal wound infections appeared a median of 10 days postoperatively (interquartile range, 7-14 d; range 3-100 d). Vacuum-assisted closure was applied a median of 13 days postoperatively (interquartile range, 10-18.5 d; range, 5-103 d) for a median duration of 10 days (interquartile range, 7-13.25 d; range, 1-21 d). Wound cultures were positive in 48 patients (96%); most isolates were Gram-positive (76%). The main bacterial pathogen was methicillin-susceptible Staphylococcus aureus (61%). Most patients were treated with cloxacillin for a median of 38 days (interquartile range, 28-42 d; range, 9-189 d). There were no statistically significant differences in clinical or treatment characteristics between bacteremic (56%) and nonbacteremic patients. Compared with older patients, infants less than 3 months old (36%) had a significantly longer hospitalization time (41 vs 25 d; p = 0.001) and higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category (3 vs 2; p = 0.003). All cases except one (contact dermatitis) were uneventful. In 10 patients, wounds were closed surgically after vacuum-assisted closure. Two patients required a pectoralis flap, both treated before 2005. One of the two deaths was infection-related.

Conclusions: Vacuum-assisted closure is a feasible treatment option of deep sternal wound infection after pediatric cardiac surgery and was not associated with independent morbidity.
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February 2020

Flavobacteriaceae Bacteremia in Children: A Multicenter Study.

Pediatr Infect Dis J 2019 11;38(11):1096-1099

From the Department of Pediatrics B, Schneider Children's Medical Center, Petach Tikva, Israel.

Background: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections.

Methods: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018.

Results: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin.

Conclusions: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.
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November 2019

Atypical presentation of human ehrlichiosis and anaplasmosis in children in Israel.

Acta Paediatr 2019 09 17;108(9):1727-1728. Epub 2019 Jun 17.

Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

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September 2019

Pediatric Infectious Sacroiliitis: Characterization and Differentiation from Noninfectious Etiologies.

Pediatr Infect Dis J 2019 07;38(7):e134-e137

From the Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva.

Background: Pediatric sacroiliitis (SI) is an uncommon entity of infectious or inflammatory etiology. Recent data regarding pediatric SI are scarce. The study objective was to describe and compare the clinical features of pediatric infectious and noninfectious SI.

Methods: We reviewed files of children ≤18 years of age, admitted with SI in 2004-2017. Patients were grouped by etiology, infectious versus noninfectious. Clinical and laboratory indices, imaging, treatment protocols and outcome were compared.

Results: Study population included 40 patients with infectious SI (range: 3-192 months, median age: 15 months, 45% female) and 13 patients with noninfectious SI (range: 30-216 months, median age: 168 months, 62% females). Duration of symptoms before admission averaged 5.9 ± 7.5 days in the infectious group and 54.2 ± 96 days in the noninfectious group (P = 0.003). Symptoms observed solely in the infectious group included refusal to stand (n = 27, 77%); walk or crawl (n = 24, 65%); irritability (n = 20, 50%) and recent constipation event (n = 8, 20%). No significant differences in laboratory results were found. Infectious SI patients had uneventful medical history, rapid response to antibiotics and a higher rate of complete resolution of symptoms without recurrences.

Conclusions: An acute unilateral presentation in young patients ≤2 years of age, without chronic medical conditions, suggests an infectious etiology of SI anticipated to completely resolve with antibiotic treatment, not necessitating further workup for noninfectious etiologies.
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July 2019

Risk factors for early invasive fungal infections in paediatric liver transplant recipients.

Mycoses 2018 Sep 20;61(9):639-645. Epub 2018 Jun 20.

Sackler Faculty of Medicine, Tel Aviv University Tel Aviv, Israel.

Invasive fungal infections (IFIs) postliver transplantation are a frequent cause of morbidity and mortality; however, studies reporting on these infections in the paediatric population are scarce. To investigate the incidence and risk factors of IFIs in paediatric liver transplant recipients during the early posttransplantation period (≤3 months). Data were collected for all paediatric liver transplant recipients registered in a national transplantation center from 2004 to 2014. Using a stepwise logistic regression to identify independent risk factors for IFIs, a predictive model was formulated. Ten IFIs were identified in 81 liver transplant recipients (12.3%) all occurring during the first month posttransplantation. Candida species were responsible for nine cases (90%), of which four were non-albicans Candida (44%). Significant risk factors were identified; recipient of multiple blood product transfusions during transplantation, prolonged use of indwelling intravenous catheter, prolonged IV antibiotic treatment, surgical complications, pulse steroid treatment and living donor liver transplantation. The predictive model used two clinical parameters to define high-risk patients: a living donor transplantation and duration of IV antibiotic treatment (area under the ROC curve 0.918). IFIs are a significant complication occurring in the first month posttransplantation. Future studies are required to assess efficacy of targeted antifungal prophylaxis in high risk patients.
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September 2018

Fusobacterium necrophorum as an Emerging Pathogen of Acute Mastoiditis.

Pediatr Infect Dis J 2019 01;38(1):12-15

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Recent reports have reported an increase in the incidence of acute mastoiditis because of Fusobacterium necrophorum. However, the crude incidence and the specific clinical and laboratory characteristics of F. necrophorum mastoiditis in children have not been described. Our aim was to describe these features to identify high-risk patients.

Methods: The electronic medical records of all children with acute mastoiditis at a tertiary medical center between July 2011 and December 2015 were analyzed. Using a stepwise logistic regression to identify independent risk factors for F. necrophorum, we formulated a predictive model.

Results: F. necrophorum was identified in 13% (19/149) of mastoiditis cases with an identifiable agent. Its incidence increased 7-fold from 2.8% in 2012 to 20.4% in 2015 (P = 0.02). F. necrophorum infection had unique clinical, laboratory and prognostic features. The vast majority had complications and underwent surgical intervention. The predictive model used 4 parameters to define high-risk patients for F. necrophorum infection at admission: females, winter/spring season, prior antibiotic treatment and a C-reactive protein value >20 mg/dL (area under receiver operating characteristic curve 0.929).

Conclusions: Clinicians should be aware of the increasing incidence of F. necrophorum mastoiditis and consider anaerobic cultures and specific anaerobic coverage in high-risk patients.
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January 2019

Long-term immunity to hepatitis B following vaccination in infancy: Real-world data analysis.

Vaccine 2018 04 21;36(17):2288-2292. Epub 2018 Mar 21.

Tel Aviv University, Sackler School of Medicine, 55 Chaim Levanon St., Tel Aviv 69978, Israel; Maccabi Health Care Services, Maccabi Institute of Health Services Research, 27 Ha'Mered St., Tel Aviv 68125, Israel; Schneider Children's Medical Center of Israel, Infectious Disease Unit, 14 Kaplan St., Petach Tikva 49202, Israel. Electronic address:

Background: Hepatitis B virus (HBV) vaccination has decreased the prevalence of chronic HBV infections and their sequelae. However, whether vaccination at birth provides lifelong protection is unclear.

Objective: To assess long-term immunity following neonatal HBV immunization in a large population-based cohort.

Methods: Using the database of a 2 million member sick fund in Israel, we identified all subjects born after introduction of universal HBV vaccination in Israel (January 1992 through December 2014), that were tested for hepatitis B surface antibody (anti-HBs Ab's). Years since vaccination were categorized into 5-year groups and linear trends in the seroprevalence of HBV immunity were calculated. Anamnestic response and presence of Hepatitis B surface antigen (HBs Ag) were assessed.

Results: Included were 20,634 tested individuals. Mean (±SD) age at testing was 14.8 (±5.4) years. Mean anti-HBs Ab levels declined with time to 16.39 mIU/ml in the 15-20 year group (P < 0.001). The proportion of negative results increased gradually (P < 0.001) to 66.7% after 15 years. Anamnestic response assessment showed that 604 of 644 seronegative subjects (93.8%, 95% CI: 91.6-95.5%) became seropositive after a booster dose. HBs Ag was identified in 91 of the 20,634 (4.4 per 1000 study participants).

Conclusions: Following vaccination, anti-HB's Ab's progressively decline, with only a third of the population retaining protective levels after 15 years. In adolescence, anamnestic response shows that nearly all revaccinated adolescents exhibit immunity. A low rate of Hepatitis B infection was demonstrated despite vaccination of nearly all newborns.
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April 2018

Blood Cultures Drawn From Arterial Catheters Are Reliable for the Detection of Bloodstream Infection in Critically Ill Children.

Pediatr Crit Care Med 2018 05;19(5):e213-e218

Department of Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objectives: Arterial catheters may serve as an additional source for blood cultures in children when peripheral venipuncture is challenging. The aim of the study was to evaluate the accuracy of cultures obtained through indwelling arterial catheters for the diagnosis of bloodstream infections in critically ill pediatric patients.

Design: Observational and comparative.

Setting: General and cardiac ICUs of a tertiary, university-affiliated pediatric medical center.

Patients: The study group consisted of 138 patients admitted to the general or cardiac PICU in 2014-2015 who met the following criteria: presence of an indwelling arterial catheter and indication for blood culture.

Interventions: Blood was drawn by peripheral venipuncture and through the arterial catheter for each patient and sent for culture (total 276 culture pairs).

Measurements And Main Results: Two specialists blinded to the blood source evaluated each positive culture to determine if the result represented true bloodstream infection or contamination. The sensitivity, specificity, and positive and negative predictive values of the arterial catheter and peripheral cultures for the diagnosis of bloodstream infection were calculated. Of the 56 positive cultures, 41 (15% of total samples) were considered diagnostic of true bloodstream infection. In the other 15 (5%), the results were attributed to contamination. The rate of false-positive results was higher for arterial catheter than for peripheral venipuncture cultures (4% vs 1.5%) but did not lead to prolonged unnecessary antibiotic treatment. On statistical analysis, arterial catheter blood cultures had high sensitivity (85%) and specificity (95%) for the diagnosis of true bloodstream infection, with comparable performance to peripheral blood cultures.

Conclusion: Cultures of arterial catheter-drawn blood are reliable for the detection of bloodstream infection in PICUs.
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May 2018

Influenza Vaccination Rate and Reasons for Nonvaccination in Children With Cardiac Disease.

Pediatr Infect Dis J 2017 Nov;36(11):e268-e271

From the *Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; †Unit of Pediatric Infectious Diseases, ‡Pediatrics A, and §Institute of Pediatric Cardiology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Influenza is a major cause of respiratory morbidity worldwide. It poses a risk of complications in children with cardiac disease. Influenza vaccine is considered the most effective and safe means of preventing the disease. The aims of this study were to determine the rate of influenza vaccination in children with cardiac disease and to identify the reasons for failure to vaccinate in this patient population.

Methods: The study group included 186 children and their parents who attended the cardiology institute of a tertiary pediatric medical center between September and October 2012. Parents were asked to complete a questionnaire covering demographics, clinical features, influenza vaccination, receipt of advice from medical professionals regarding vaccination and personal knowledge about and attitude toward the influenza vaccine.

Results: Median age of the children was 7.6 years. Thirty-six percent had been vaccinated in the previous influenza season. Vaccination was unrelated to the child's age or sex or the parents' education. Factors significantly affecting the decision of the parents to have their child vaccinated were their knowledge, beliefs and conceptions about the vaccine and their receipt of a recommendation to do so from the pediatrician or cardiologist (P < 0.001).

Conclusions: The rate of vaccination against influenza is low in children with heart disease. Major factors encouraging vaccination are proper parental knowledge and the recommendation of the primary physician or cardiologist. Medical professionals caring for this patient population should be alerted to the need to routinely counsel parents on the importance of influenza vaccination.
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November 2017

Dual versus Triple Antibiotics Regimen in Children with Perforated Acute Appendicitis.

Eur J Pediatr Surg 2018 Dec 25;28(6):491-494. Epub 2017 Sep 25.

Department of Pediatric Surgery, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Introduction:  Acute appendicitis is the most common emergency condition in pediatric surgery. Historically, a triple-antibiotic therapy consisted of ampicillin, gentamicin, and clindamycin has been used postoperatively for perforated appendicitis. According to recently published trials, dual therapy consists of ceftriaxone and metronidazole only, offers a more efficient and cost-effective antibiotic management compared with triple therapy. Based on these results, our department applied dual antibiotic therapy for children with perforated appendicitis that underwent appendectomy from 2009 and forth.

Aim:  The aim of our study was to compare postoperative outcomes between patients treated with triple therapy (ampicillin, gentamicin, and metronidazole) (group A) versus dual therapy (ceftriaxone and metronidazole) (group B).

Methods:  Clinical and laboratory data were retrospectively collected by review of the medical records for all children who underwent appendectomy for the perforated appendix at the Schneider Children's Medical Center of Israel, a tertiary pediatric care center between 2007 and 2011. Children with perforated appendicitis received antibiotic therapy in accordance with the hospital's guidelines that were valid at the time the surgery took place. In the first period (years 2007-2009) (group A) a triad of ampicillin, gentamicin, and metronidazole and the second period (2009-2011) (group B) dual therapy consists of ceftriaxone and metronidazole. The two groups were compared for outcome and complications, such as wound infections, changing of antibiotic therapy, and length of stay.

Results:  During the study period 1,203 patients underwent an appendectomy. Of these, 175 patients were diagnosed with perforated appendix and were treated with postoperative antibiotic's regimen. Group A and group B consisted of 89 and 86 patients, respectively. The two groups were not different significantly in terms of demographic data, length of stay, or readmission rates. However, more rates of wound infection and changing of antibiotic therapy were seen in group B, although not statistically significant ( = 0.064).

Conclusion:  Dual antibiotic therapy for perforated appendicitis is a cost-effective and efficient mode of therapy compared with triple-antibiotic's regimen. However, prospective studies are required to determine whether this policy is associated with higher rates of wound infections and change in antibiotic therapy.
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December 2018

Chronic Q Fever Infections in Israeli Children: A 25-year Nationwide Study.

Pediatr Infect Dis J 2018 03;37(3):212-217

Background: Q fever is a zoonosis caused by the bacterium Coxiella burnetii (C. burnetii) with a worldwide distribution. Our aim was to assess the epidemiology, clinical manifestations and treatment regimens of chronic Q fever infections in Israeli children during the past 25 years.

Methods: Cases were collected from the national Q fever reference laboratory database. Demographic, epidemiologic and clinical data were reviewed using a structured questionnaire sent to the referring physician. Cases were defined according to the new Dutch Consensus Guidelines.

Results: A total of 16 children originating from all regions of the country were found positive for chronic Q fever infections. The most common infection site was bone or joint (8/16, 50%), all in previously healthy children. Endovascular infections were found in 5 children (31%), all with an antecedent cardiac graft insertion. According to the new Consensus Guidelines, 9 children (56%) had a proven infection, 3 (19%) a probable infection and 4 (25%) a possible chronic Q fever infection. Almost all cases were treated with a long-term antibiotic regimen, often necessitating a change in medication because of persistent or rising titers.

Conclusions: Although pediatric chronic Q fever infections are rare, incidence has been rising. The most common infection site was bone or joint. A high index of suspicion is necessary, even in cases of previously healthy children without a possible exposure history. Use of the relatively new diagnostic tools in combination with serologic methods is helpful in diagnosing proven cases. There is no consensus as to the selection or duration of antibiotic treatment.
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March 2018

Nephrologists need to play a key role in improving annual influenza vaccination rates in children with kidney disease.

Acta Paediatr 2017 May 23;106(5):812-818. Epub 2017 Feb 23.

Pediatric Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: This study investigated the under-researched area of annual influenza vaccination rates in children with chronic kidney disease and identified reasons for nonimmunisation.

Methods: A prospective cross-sectional study was conducted in the nephrology clinic and dialysis unit of a tertiary paediatric medical centre from August to October 2011 and September to October 2012. Parents were asked to complete a questionnaire on their child's immunisation against influenza.

Results: Of the 217 children studied, 45.6% were vaccinated against influenza. The major reason for nonimmunisation was because the parents had not received the necessary information from the primary physician or treating nephrologist. The nonvaccinated children were significantly more likely to be less than two years old and female and to have parents who did not believe in the benefits of vaccination (p < 0.05). Of the parents who did not vaccinate their child, 38% claimed they would have done so if the vaccine had been offered in the nephrology clinic.

Conclusion: Children with kidney disease had a higher annual influenza vaccination rate than the general population, but it was still suboptimal. Nephrologists should be alerted to the need to provide parents with information on influenza vaccinations and they should be available in nephrology clinics.
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May 2017

Positive IgM in Congenital CMV Infection.

Clin Pediatr (Phila) 2017 Apr 22;56(4):371-375. Epub 2016 Dec 22.

1 Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.

Neonatal serum detection of cytomegalovirus (CMV) immunoglobulin M (IgM) has low sensitivity in identifying congenital cytomegalovirus (cCMV). Several reports have endeavored to associate the presence/absence of IgM to disease severity. Data were collected for all infants with cCMV followed in our clinic. Infant outcome after birth was compared between infants who tested positive or negative. Sensitivity of positive IgM in diagnosing cCMV was 40.7%. The rate of symptomatic disease in those who tested positive was statistically higher (67.7%, P < .001). Odds ratio for symptomatic disease in infants with positive IgM born after a maternal primary infection was 3.47 (95% confidence interval = 1.7-7.1). Positive IgM was found in only 48.8% of symptomatic and 22.1% of asymptomatic children. Our results demonstrated a low sensitivity of IgM in diagnosing cCMV. However, while a positive IgM antibody for CMV is associated with a more symptomatic disease, it does not serve as a precise laboratory marker for a severity.
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April 2017

Human metapneumovirus (hMPV) infection in immunocompromised children.

J Clin Virol 2016 10 17;83:12-6. Epub 2016 Jun 17.

Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Ramat Aviv 6997801, Israel.

Background: Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory tract infection (URTI, LRTI) in children. The prognosis of hMPV is unclear in immunocompromised patients.

Objectives: To describe the characteristics of hMPV infection in immunocompromised pediatric patients and to review the literature.

Study Design: This retrospective study included 39 immunocompromised children (age 0-18 years) with proven hMPV infection attending two tertiary pediatric medical centers in 2004-2014. Demographic, clinical, laboratory, and radiological data were collected from the medical files.

Results: Median age was 6 years. Seven patients had primary immune deficiency and 32, secondary immune deficiency, including 9 patients who underwent hematopoietic stem cell transplantation (HSCT). Most cases (92%) occurred in January-May. Twenty patients (51%) had lower respiratory tract infection and 17 (44%), upper respiratory tract infection; 2 patients (5%) had fever only. Presenting symptoms were fever (70%), cough (54%), and rhinorrhea (35%). Severe lymphopenia (<1000lymphocytes/mL) was noted in 64% of patients and elevated liver enzyme levels in 49%. Seventeen patients had pneumonia: bilateral and alveolar in 13 patients, each. HSCT was not associated with more severe disease. Respiratory failure occurred in 6 patients, of whom 4 died (10% of cohort). All children who died had severe lymphopenia. On multivariate analysis, bacterial or fungal co-infection was the only major risk factor for death. Review of the literature showed variable clinical presentations and severity in pediatric patients with hMPV infection.

Conclusions: Infection with hMPV may be associated with relatively high morbidity and mortality in immunocompromised children. Death was associated with bacterial and fungal co-infection.
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October 2016

Clinical Implications for Children Born With Congenital Cytomegalovirus Infection Following a Negative Amniocentesis.

Clin Infect Dis 2016 07 24;63(1):33-8. Epub 2016 Apr 24.

Department of Pediatrics C, Schneider Children's Medical Center, Petah Tiqva Sackler Faculty of Medicine, Tel Aviv University.

Background: Recently, congenital cytomegalovirus (cCMV) infection was reported irrespective of a negative amniotic fluid prenatal analysis for cytomegalovirus (CMV). The question of whether this phenomenon represents low sensitivity of the test or late development of fetal infection (after amniocentesis) was discussed, but not answered. However, if late transmission is the rule, then infants born with cCMV after negative amniocentesis would be expected to carry better prognosis than those who tested positive.

Methods: Data of all infants with cCMV infection, followed in 2 pediatric centers from 2006 to 2015, were reviewed. Infant outcome after birth of symptomatic vs asymptomatic disease was compared with infants born after a negative amniocentesis (study group) and those with a positive amniocentesis (control group).

Results: Amniocentesis was performed in 301 pregnancies of our cohort of infants with cCMV and was negative for CMV in 47 (15.6%). There were fewer symptomatic cCMV neonates in the study group than in the control group (4.3% vs 25%; P < .001). Hearing impairment at birth was also less frequent in the study group (2.2% vs 17.4%; P = .012). None of the children in the study group had neurologic sequelae at long-term follow up, compared with 13 (14.1%) in the control group (P < .001).

Conclusions: Although negative amniocentesis does not exclude cCMV, infants with cCMV born after a negative amniocentesis seldom present with mild clinical symptoms or cerebral ultrasound features at birth. These children also have a very good long-term outcome. Our findings support the theory of a late development of fetal infection, after the time of the amniocentesis.
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July 2016

Lenticulostriated vasculopathy is a high-risk marker for hearing loss in congenital cytomegalovirus infections.

Acta Paediatr 2015 Sep 22;104(9):e388-94. Epub 2015 Jun 22.

Department of Pediatrics C, Schneider Children's Medical Center, Petah Tiqva, Israel.

Aim: This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection.

Methods: We included all infants with cCMV infection who were followed in our clinic for more than a year with only LSV signs of brain involvement on initial brain ultrasound. Group one comprised 13 infants with no hearing impairment at birth who were not treated with gan/valganciclovir during 2006-2009. Group two was 51 infants with LSV and no hearing impairment who had been treated since mid-2009. Group three was 25 infants born with LSV and hearing loss, who had been treated from birth. Group four was 52 control infants born during the same period with asymptomatic cCMV. Hearing tests were performed during the neonatal period and every four to six months until four years of age.

Results: Hearing deterioration was more extensive in group one (85%) than in group two (0%, p < 0.001) and the asymptomatic group (10%, p < 0.001) and occurred more often in group four (10%) than in group two (0%, p = 0.008).

Conclusion: Lenticulostriated vasculopathy was common in infants with cCMV infection and may serve as a sign of central nervous system involvement and further hearing deterioration. Antiviral treatment may be prudent in such infants.
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September 2015

Cervical Discitis in Children.

Pediatr Infect Dis J 2015 Jul;34(7):794-5

From the *Department of Pediatrics B, †Pediatric Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ‡Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; §Department of Imaging, and ¶Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Cervical discitis, though rare, should be included in the differential diagnosis of torticollis, neck pain and neurodevelopmental regression in motor skills in children and infants. Magnetic resonance imaging is the diagnostic method of choice. Treatment should be conservative with antibiotics only. The aim of this study was to describe the 10-year experience of a tertiary pediatric medical center with cervical discitis.
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July 2015

Seasonal influenza vaccination rates and reasons for non-vaccination in children with gastrointestinal disorders.

Vaccine 2015 Jan 11;33(1):182-6. Epub 2014 Nov 11.

Sackler Faculty of Medicine, Tel.: Aviv University, Tel: Aviv, Petach Tikva, Israel; Unit of Pediatric Infectious Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel. Electronic address:

Objectives: Despite advances in the treatment and prevention of influenza, it is still considered an important cause of morbidity and mortality worldwide. Annual vaccination is the safest and most effective mean of prevention. Our study aims were to explore the uptake of influenza vaccination among children with gastrointestinal disorders, and to characterize non-adherent patients.

Methods: The present cross-sectional study included parents of pediatric patients attending the Gastroenterology Institute at Schneider Children's Medical Center of Israel between September and October 2011. Parents were asked to complete a questionnaire concerning demographic and clinical parameters, influenza vaccination of the child, and reasons for not vaccinating the child, when appropriate.

Results: The study population included 273 patients (50% female), with a median age of 10 years (range, 2-18 years). Overall, the rate of seasonal influenza vaccination was 30.8%. Higher rates were found among immunosuppressed patients (46.1%), and in patients with inflammatory bowel disease (50%). There was no significant effect of patient age, gender, ethnic origin or parental level of education on the vaccination rate. Vaccination rates were significantly associated with parents' information and knowledge of, as well as their personal beliefs regarding the vaccine (P<0.001).

Conclusions: Influenza vaccination rates are relatively low in the pediatric population attending gastroenterology clinics, in both high- and low-risk groups. The importance of parental knowledge in compliance with influenza vaccination of children should prompt general pediatricians and gastroenterologists to discuss and address the common misconceptions regarding the vaccine.
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January 2015

Compliance with surgical antibiotic prophylaxis guidelines in pediatric surgery.

Eur J Pediatr Surg 2015 Apr 28;25(2):199-202. Epub 2014 Mar 28.

Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.

Introduction: Surgical antibiotic prophylaxis (AP) guidelines balance the need to prevent infection with the risks of adverse drug effects. Our aim was to assess compliance with AP guidelines.

Methods: A retrospective study was performed in a pediatric medical center. Included were patients aged 0 to 18 years that underwent clean-contaminated surgery during a 1-year period (2008-2009) and required AP. Compliance with four AP bundle guidelines was evaluated. Risk factors for noncompliance were identified using univariate and multivariate analyses.

Results: AP was given to 239 of 247 (96.8%) of patients. Complete compliance with AP guidelines was achieved in 16 of 247 (6.5%) patients. Compliance with guidelines for appropriate antibiotic, drug dose, correct timing, and treatment duration were found in 97.1, 52.2, 31.9, and 35.9% of patients, respectively. Multivariable analysis showed that inappropriate timing was associated with age ≥ 4 years (p = 0.002), urgent surgery (p = 0.0018), surgical department AP administration (p = 0.0001), and night-time surgery (p = 0.015). Incorrect AP dose was associated with presence of comorbidities (p = 0.006). No risk factor was related to incorrect AP duration.

Conclusions: We have found a low rate of full compliance with AP guidelines. AP should only be given in the operating room. Increased awareness to AP guidelines is needed.
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April 2015

[HIV post exposure prophylaxis therapy - the experience of two major AIDS centers].

Harefuah 2013 Apr;152(4):224-9, 246

Internal Medicine B and the Altergy, Clinical Immunology and AIDS Unit, Kaplan Medical Center, Rehovot affiliated to the Medical School, Hebrew University, Hadassah, Jerusalem.

Background: During recent years, the use of antiretroviral therapy expanded beyond the treatment of HIV-infected patients. Since the outset of the HIV epidemic, antiretroviral drugs were also used for post-exposure prevention of HIV infection in health workers and implemented after possible exposure during sex. In this study, we summarize the cases from the AIDS center in the Kaplan Medical Center and the Sheba Medical Center after possible exposure to HIV (occupational or sexual).

Aim: The study aims to validate the different types of potential exposures to HIV encountered, the treatment and outcomes.

Methods: All the data regarding attendance at the AIDS Center in the Kaplan Medical Center during the years 2008-2010 for any possible HIV exposure (occupational or sexual) and for sexual exposure in the Sheba Medical Center AIDS Clinic during the years 2003-2008 was collected retrospectively.

Results: During the years of the study, 448 patients attended the Kaplan Medical Center for consultation after a potential exposure to HIV; 314 of the cases were because of occupational exposure, however, only in 11 (3.5%) of the cases, post exposure prophylaxis (PEP) treatment was advised. In the other 134 patients who attended for non-occupational potential exposure to HIV (18 cases of needle stick or sharp object injury and 116 of sexual exposure), for 46 (40%) of these cases, PEP was recommended. No evidence of HIV infection was found for any of the 448 patients who attended the clinic for possible exposure to HIV, regardless of the consultation that they received. In the Sheba Medical Center, during the years 2003-2008, 175 patients attended for consuLtation after potential sexual exposure to HIV. The medical staff of the clinic decided, after risk assessment, to recommend PEP to 140 (80%) of the cases. Similarly, in this case, no evidence of HIV infection was found (regardless of whether PEP was given or not).

Discussion: In potential occupational exposure to HIV it is possible, in most cases, to assess the risk for infection sufficiently so that only a few cases will need PEP. In potential sexual exposure to HIV, there are many cases where data regarding the potential source of infection is partial or missing, making the risk assessment more difficult. This may be the reason for the high percentage of patients in this situation who received PEP. From the data in this study, our cohort support PEP as being effective and safe.
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April 2013

Polymerase-chain-reaction-based diagnosis of viral pulmonary infections in immunocompromised children.

Acta Paediatr 2013 Jun 28;102(6):e263-8. Epub 2013 Mar 28.

Pediatric Intensive Care Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: Viral pneumonia is a serious complication in immunocompromised children. Its aetiology is difficult to identify owing to the limitations of conventional microbiological tests. The aim of this study was to determine whether polymerase chain reaction (PCR) assays for respiratory viruses increase the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised children.

Methods: BAL samples obtained from immunocompromised children hospitalized with pneumonia were processed for respiratory viruses by viral culture, rapid antigen test and PCR (for CMV, adenovirus, influenza, parainfluenza, herpesvirus, RSV and hMPV).

Results: The study group included 42 patients (mean age 7.2 ± 5.1 years) with 50 episodes of clinical pneumonia (50 BAL samples). Forty viral pathogens were identified in 30 episodes (60%). PCR increased the diagnostic rate by fourfold (75% identified by PCR alone, p < 0.0001). When viral culture and rapid antigen test were used as the gold standard, PCR was found to have high sensitivity (86-100% when assessed) and specificity (80-96%). The PCR results prompted the initiation of specific antiviral therapy and the avoidance of unnecessary antibiotic treatment in 17 (34%) episodes.

Conclusion: PCR-based diagnosis from BAL may increase the rate of pathogen detection in immunocompromised children, decrease the time to diagnosis and spare patients unnecessary antimicrobial treatment.
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June 2013

Diagnostic accuracy of PCR alone compared to galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis: a systematic review.

J Clin Microbiol 2012 Nov 5;50(11):3652-8. Epub 2012 Sep 5.

Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.

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.
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November 2012