Josef Ben-Ari

Use of the NOW Streptococcus pneumoniae urinary antigen test in cerebrospinal fluid for rapid diagnosis of pneumococcal meningitis

Streptococcus pneumoniae is one of the most common pathogens in bacterial meningitis. Rapid diagnosis is critical for effective treatment. The aim of this study was to assess the accuracy of the NOW S. pneumoniae Urinary Antigen Test, (Binax, Portland, ME, USA) originally developed for urine testing, in detecting the S. pneumoniae antigen in cerebrospinal fluid (CSF). The study included 519 patients with suspected meningitis. CSF, blood and urine samples were cultured according to standard methods. CSF viral culture was also performed. CSF and urine specimens were tested for pneumococcal antigen with the NOW S. pneumoniae test.S. pneumoniae was isolated from the CSF of 22 patients. The direct antigen test was positive in CSF in 21/22 patients (95.4% sensitivity), and in urine, in 12/21 (57.1% sensitivity). Direct CSF smear was positive in 15/22 (68% sensitivity). CSF samples that cultured negative for S. pneumoniae (n = 470) or positive for other bacteria (n = 27) were also negative on the NOW test (100% specificity). By contrast, urine samples of 63/470 of patients with negative CSF culture were positive on the NOW test, as were 5/27 urine samples of patients with CSF culture positive for other bacteria (p = 0.45). The NOW S. pneumoniae antigen test in CSF yields a rapid and very reliable diagnosis of pneumococcal meningitis, enabling prompt and adequate treatment. Its low sensitivity in urine indicates that this mode of testing is not useful for the diagnosis of pneumococcal meningitis. These data have been included in the FDA application for approval of the NOW test for use in the CSF for the diagnosis of pneumococcal meningitis.

Chronic granulomatous disease in Israel : Clinical, functional and molecular studies of 38 patients

Chronic granulomatous disease (CGD) is an innate immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. In the course of 21 years, 38 Israeli CGD patients were diagnosed with 17 gene mutations, seven of which were new. Clinical, functional, and molecular studies were accomplished. Although X-linked recessive (XLR)-CGD is worldwide the most common genotype of the disease (~70%), in our study only 11 patients (29%) suffered from XLR-CGD. In Israel, the higher incidence of the autosomal recessive (AR) form of CGD (63%) may be related to consanguineous marriages. In three patients (8%), all four proteins of the NADPH oxidase were present. Severe clinical expression was found both in the XLR and AR forms, but in general a milder disease was evident in AR-CGD, particularly in patients with p47(phox) deficiency. Despite early and aggressive therapy, a mortality rate of 26% was noted. Given that bone-marrow transplantation was successful in five of seven patients, it is recommended to perform it as early as possible before tissue damage is irreversible.

Hemophagocytic lymphohistiocytic syndrome: Unrecognized cause of multiple organ failure.

Objective To describe an often-unrecognized clinical picture of multiple organ failure in hemophagocytic lymphohistiocytic syndrome (HLS). Design Retrospective chart review. Setting A ten-bed pediatric intensive care unit (PICU) in a tertiary children’s university hospital. Patients A total of 11 children (age, 5 months to 13 yrs) who fulfilled the criteria for the diagnosis of familial- or infectious-associated hemophagocytic lymphohistiocytosis and who required intensive care support for organ failure. Intervention None. Main Results During a 10-yr period, 5,439 children were hospitalized in our PICU. A total of 11 children were diagnosed as suffering with HLS. Of these 11 patients, three (27%) had the familial form and eight had the infectious-associated form. After admission to the PICU, seven patients (63%) were diagnosed as suffering with HLS and each had one or more organ failures (patients 3–7, 9, and 10). All presented with fever, hepatomegaly, and splenomegaly; in addition, all had at least two of the following: anemia, neutropenia, or thrombocytopenia. All 11 had lymphohistiocytic accumulation in bone marrow (n = 10), lymph node (n = 2), lung (n = 2), and/or liver (n = 1). Organ failure was noted most often in the respiratory system (n = 7) attributable to severe, acute respiratory distress syndrome and pleural effusion. Of the 11 patients, six had cardiovascular involvement that manifested as shock in three and as capillary leak syndrome in three. Renal failure occurred in four patients. Of these, two required hemodiafiltration and one required peritoneal dialysis. Liver failure occurred in three and central nervous system involvement and coma in three. Most of the patients required massive therapeutic intervention, including assisted ventilation (n = 6), inotropic support (n = 3), and hemofiltration (n = 3). A total of seven patients (63%) died. Conclusions Hemophagocytic lymphohistiocytic syndrome in the pediatric population may have a dramatic clinical picture, with multiple organ failure as a presenting symptom or early in the disease course, mandating intensive support in the PICU.

Blood Transfusion Policy among European Pediatric Intensive Care Physicians

The objective of this study was to define current blood transfusion practices among European pediatric intensive care physicians treating critically ill children. A questionnaire of case scenarios was administered to members of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Of the 258 members of the ESPNIC, 134 (51.9%) pediatric intensive care physicians completed the questionnaire. The suggested blood transfusion thresholds for case scenario 1 (post–orthopedic surgery child) ranged from <7.0 g/dl to 11 g/dl. A total of 57.3% suggested 7 g/dl, 33.6% suggested 8 g/dl, and 6.9% suggested 9 g/dl as a hemoglobin threshold for transfusion (mean, 7.54 ± 0.75). For case scenarios 2 to 4, the suggested hemoglobin thresholds were 7 g/dl to 12 g/dl. For case scenario 2 (a child with acute respiratory distress syndrome), 22.4% suggested 8 g/dl, 15.7% suggested 9 g/dl, and 41% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 9.40 ± 1.27 g/dl). For case scenario 3 (a post–cardiac surgery infant), 20.1% suggested 7 g/dl, 24.6% suggested 8 g/dl, 21.6% suggested 9 g/dl, and 23.9% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 8.72 ± 1.24 g/dl). For case scenario 4 (a child with septic shock), 23.1% suggested 8 g/dl, 16.4% suggested 9 g/dl, and 41% suggested 10 g/dl as a hemoglobin threshold for transfusion (mean, 9.45 ± 1.24 g/dl). The threshold for transfusion was not statistically different ( P > .05) between the physicians according to their subspecialty, years of experience, or country of origin. The suggested volume of transfused blood was 10 to 15 ml/kg in 427 responses (82.6%) and 20 ml/kg in 89 responses (17.2%). Most physicians, 78/128 (60.9%), did not consider the age of the transfused blood an important factor in their decision to transfuse. Of the 106 (79.1%) physicians who detailed their considerations for elevating the thresh- old for transfusion, 82 (77.3%) gave a general nonspecific indication, 47 (44.3%) stated hemodynamic instability and shock, and 40 (37.7%) an ongoing bleeding. The hemoglobin threshold for blood transfusion and transfusion volume varies among European pediatric intensive care physicians, for the same patient.

Infections associated with chronic granulomatous disease: linking genetics to phenotypic expression

Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency characterized by the absence or malfunction of the NADPH oxidase in phagocytic cells. As a result, there is an impaired ability to generate superoxide anions and the subsequent reactive oxygen intermediates. Consequently, CGD patients suffer from two clinical manifestations: recurrent, life-threatening bacterial and fungal infections and excessive inflammatory reactions leading to granulomatous lesions. Although the genotype of CGD was linked to the phenotypic expression of the disease, this connection is still controversial and poorly understood. Certain correlations were reported, but the clinical expression of the disease is usually unpredictable, regardless of the pattern of inheritance. CGD mainly affects the lungs, lymph nodes, skin, GI tract and liver. Patients are particularly susceptible to catalase-positive microorganisms, including Staphyloccocus aureus, Nocardia spp. and Gram-negative bacteria, such as Serratia marcescens, Burkholderia cepacea and Salmonella spp. Unusually, catalase-negative microorganisms were reported as well. New antibacterial and antimycotic agents considerably improved the prognosis of CGD. Therapy with IFN-γ is still controversial. Bone marrow stem cell transplantation is currently the only curative treatment and gene therapy needs further development. In this article, the authors discuss the genetic, functional and molecular aspects of CGD and their impact on the clinical expression, infectious complications and the hyperinflammatory state.

Vocal fold paralysis in infants with tracheoesophageal fistula.

Objectives: We describe the clinical characteristics and management of vocal fold paralysis in infants who were born with a tracheoesophageal fistula (TEF). Methods: This retrospective case series included all infants born with TEFs who presented to our pediatric otolaryngology unit and intensive care unit because of dyspnea or aphonia in the years 2005 and 2006, and who were found to have vocal fold paralysis. Results: Five boys and 1 girl were studied. One infant had stridor before TEF repair, and 5 after it. All children underwent flexible laryngotracheobronchoscopy and were treated in the pediatric intensive care unit before diagnosis of the vocal fold paralysis (5 bilaterally and 1 unilaterally) was made. The ages at diagnosis of paralysis ranged between 14 days and 14 months. Five infants required tracheostomy. Conclusions: Vocal fold paresis in infants is difficult to diagnose. The risk for recurrent laryngeal nerve injury associated with TEF and TEF repair should be emphasized in these children. We recommend that all newborns with TEF should be examined by an otolaryngologist before operation to confirm the mobility of the vocal folds and to rule out other associated airway malformations, and examined after operation if respiratory difficulties develop.

Laryngomalacia: a cause for early near miss for SIDS

Six infants had recurrent apnea of infancy episodes (near miss sudden infant death syndrome) during their neonatal period. Physical examination and laboratory investigation were normal. Polygraphic sleep monitoring revealed recurrent obstructive sleep apnea. These infants underwent fiberoptic endoscopy which showed that airway obstruction occurred at the laryngeal orifice as a result of laryngomalacia. It is suggested that laryngomalacia may be a cause for early apnea of infancy.

Hepatitis Associated with Propylthiouracil Treatment

A 12-year-old girl with hyperthyroidism who had started treatment with propylthiouracil (PTU) 100 mg tid developed hepatitis. The drug was stopped, and the clinical and laboratory findings of hepatitis disappeared within a week. She was not receiving other drugs that could cause hepatic damage, and investigations for various viral agents were negative. This is the ninth report of PTU-induced hepatitis. The clinical picture is similar to that of viral hepatitis. Recovery usually occurs after withdrawal of the drug, but there have been two fatal cases of PTU-induced hepatitis.

Oral amphotericin B for the prevention of Candida bloodstream infection in critically ill children

Objectives: To determine the efficacy of oral amphotericin B for the prevention of Candida bloodstream infection in the pediatric intensive care unit. Design: Retrospective, nonrandomized, historic-control study. Setting: Multidisciplinary pediatric intensive care unit at a university-affiliated children’s medical center. Patients: Study group included all patients admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, who required mechanical ventilation and who were admitted for >7 days. The control group included all patients admitted for >7 days who needed mechanical ventilation from January 1, 1994, to December 31, 1997. Interventions: Oral amphotericin B suspension, 50 mg every 8 hrs, administered to all study group patients soon after initiation of mechanical ventilation and terminating after weaning. Measurements: The rates of Candida bloodstream infection were compared between the study and control groups. Main Results: Candida species were isolated from blood cultures in 5 of 185 (2.1%) and 21 of 196 (10.7%) patients in the study and control groups, respectively (p= .0038). There was also a statistically significant (p= .017) decrease in Candida bloodstream infection rate in all patients admitted to the pediatric intensive care unit for >7 days during the study period compared with the Candida bloodstream infection rate during the control period. Conclusion: Prophylactic administration of oral amphotericin B may lead to a significant decrease in the rate of Candida bloodstream infection in ventilated pediatric intensive care unit patients.

Prolonged croup due to herpes simplex virus infection

Abstract Herpes simplex virus (HSV) is an uncommon cause of acute laryngitis in immunocompetent patients since it mostly occurs in immunocompromised subjects. We present two previously healthy children with prolonged gingivostomatitis and stridor (lasting 3 and 4 weeks) in whom HSV-1 was isolated from subglottal ulcers. Conclusion HSV should be considered a possible pathogen in cases of prolonged or atypical croup not only in immunocompromised or elderly patients but also in otherwise healthy children.