Fetal intracerebral hemorrhage and cataract: think COL4A1.

The COL4A1 gene encodes the alpha1 chain of type IV collagen, a crucial component of nearly all basement membranes. Mutations in COL4A1 were first associated with cerebral microangiopathy and familial porencephaly. Recently, several authors have reported mutations in COL4A1 as a Mendelian cause of prenatal onset intracranial hemorrhage (ICH). We report two cases of prenatal ICH associated with cataract and suggest that COL4A1 mutation should be envisaged in fetuses with prenatal ICH, especially in the presence of lens abnormalities at ultrasound examination.

De novo mutations in ATP1A2 and CACNA1A are frequent in early-onset sporadic hemiplegic migraine.

OBJECTIVE: Hemiplegic migraine (HM) is a rare subtype of migraine with aura that may occur as a familial (FHM) or sporadic condition (SHM). Screening of FHM genes in previous series of patients with SHM detected a very low proportion of mutated patients. In this study, we investigated the FHM genes in patients with an early onset sporadic form of HM (onset before 16 years). METHODS: Twenty-five patients were included. Each one and his or her 2 parents were blood sampled. Mean age at diagnosis was 14.7 ± 8.2 years and mean age at clinical onset was 7.7 ± 3.4 years. Sequencing of ATP1A2 and CACNA1A was conducted in each proband and all identified variants were looked for in both parents. SCN1A was screened in all patients without CACNA1A or ATP1A2 de novo mutation. RESULTS: Twenty-three different amino acid variants were identified in 23 of the 25 patients. The variants occurred de novo in 19 patients (76%), strongly in favor of their causal role. SCN1A analysis did not show any mutation. Among the 19 patients with a de novo mutation, 5 had a pure HM and 14 had associated neurologic signs such as ataxia, epilepsy, or intellectual disabilities. CONCLUSIONS: FHM genes are involved in early-onset SHM, in particular when associated with neurologic signs. Molecular analysis can be helpful in those cases. Our study identified 14 novel de novo mutations that will help to interpret genetic tests in molecular diagnosis practice.

Streptococcus pneumoniae thoracic empyema in children: rapid diagnosis by using the Binax NOW immunochromatographic membrane test in pleural fluids.

AIM: To evaluate an immunochromatographic membrane test for Streptococcus pneumoniae antigen (Binax NOW, Inverness medical France) applied to pleural fluid samples. METHODS: Binax NOW was applied to the pleural fluids of 69 children with thoracic empyema, in comparison with conventional culture and molecular techniques. RESULTS: Binax NOW was positive on all 15 pleural fluid samples that yielded S. pneumoniae in culture, on two samples that yielded S. oralis and S. salivarius in culture and on 34 culture-negative samples. Fifteen of these 34 culture-negative samples were retrospectively tested by PCR methods, and 14 were shown to contain S. pneumoniae DNA. Thus, S. pneumoniae was identified by culture in 22% of samples and by Binax NOW in 69% of samples. CONCLUSION: Binax NOW may thus be useful for rapid diagnosis of S. pneumoniae thoracic empyema.

Low incidence of sepsis due to viridans streptococci in a ten-year retrospective study of pediatric acute myeloid leukemia.

BACKGROUND: Infections remain an important cause of morbidity and mortality in children with acute myeloid leukemia (AML), and particularly viridans group streptococci (VGS) sepsis. The present study, conducted between 1993 and 2003 in children with AML, sought to assess the frequency and characteristics of infectious complications (ICs), the incidence of VGS sepsis, the interest of preventive decontamination, and a possible cytarabine dose-effect on the occurrence of ICs. METHODS: Medical charts of 78 children treated according to the EORTC 58921 clinical trial were analyzed retrospectively. Patients were isolated in laminar air flow rooms, received non-absorbable gut decontamination, gum decontamination with vancomycin mouthwash, and trimethoprim-sulfamethoxasole. ICs were categorized as microbiologically documented infections (MDI), clinically documented infections (CDI), or fever of unknown origin (FUO). RESULTS: Overall, 268 ICs occurred: 57.5% FUO, 8.5% CDI, and 34% MDI. Bloodstream infections occurred in 58 febrile episodes: Gram-positive bacteria represented 83% of the pathogens including 66.1% Staphylococcus species and 8.5% Streptococcus species (6.8% VGS), Gram-negative bacteria represented 13.5% of the pathogens and yeasts 3.5%. Five patients died of infection (6.4%). None died from bacterial infection and no case of VGS sepsis required intensive care. Invasive fungal infection was proven in four patients. Number of ICs was significantly different according to gum and gut decontamination status, and according to the cytarabine dose during the first intensification. No resistant strains were detected in spite of the use of local antibiotics. CONCLUSION: The low rate of VGS and enterobacteriaceae sepsis was probably due to the effective decontamination. Our supportive care strategy could potentially help enhance overall survival in children with AML.

Rapid identification of Candida glabrata with a new commercial test, GLABRATA RTT.

The GLABRATA RTT test (Fumouze Diagnostics, Levallois Perret, France) is based on the ability of Candida glabrata to hydrolyze trehalose but not maltose. It requires an inoculum of only four to six colonies, and the results are available within 20 min. We tested GLABRATA RTT with 330 stock isolates grown in subcultures on four different primary fungal isolation media and obtained a sensitivity of 94 to 98% (depending on the medium used) and a specificity of 97.3 to 98.6%. The false-positive results corresponded to C. tropicalis, C. famata, and C. lusitaniae. GLABRATA RTT thus offers rapid and reliable identification of C. glabrata.

[Vancomycin-resistant enterococci in pediatric hematology: don't panic!]. / Entérocoques résistants á la vancomycine en hématologie pédiatrique: pas de panique!

Do immunocompromised children, carrying vancomycin-resistant enterococci (VRE) need to be treated? For 3 years, 230 children with chemotherapy and/or bone-marrow transplantation (BMT) received amikacin for gut decontamination and rinsed their mouth with solutions including vancomycin or not, according to the duration and severity of neutropenia. Some patients were isolated, others were at home with ambulatory treatment. The first-line antibio-therapy was piperacillin-amikacin-vancomycin in the chemotherapy unit, imipenem-vancomycin in the BMT unit. Once-a-week, the laboratory used to check the efficiency of decontamination procedures and look for emerging resistant bacteria. Four patients were identified as VRE carriers in their gut flora. The fecal carriage was long-lasting in a single patient, for whom attempts of eradication failed. No patient underwent VRE bacteremia. From our experience, it seems reasonable to neglect enterococcal eradication, provided that hygienic measures are strictly applied.

Pefloxacin and vancomycin vs. gentamicin, colistin sulphate and vancomycin for prevention of infections in granulocytopenic patients: a randomised double-blind study.

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

Septicemia caused by Sphingobacterium multivorum.

Sphingobacterium multivorum was isolated in pure culture from the blood of a man undergoing chemotherapy for a lymphoma. He responded to appropriate antibiotics and later showed a significant rise in specific serum antibodies. Carbon substrate assimilation tests and fatty acid analysis proved useful in identifying the organism precisely.

Nosocomial colonization and infection by Achromobacter xylosoxidans.

Achromobacter xylosoxidans, a bacterial species named in 1971, is often isolated from aqueous environments, but little has been reported about its pathogenicity in humans, its epidemiological pattern, and its susceptibility to antibiotics and antiseptics. We were faced with an epidemic caused by this microorganism for 18 months in an intensive care unit. Two patients had fatal infections and 37 others were colonized. The source was the deionized water of the hemodialysis system. The 46 isolates were identified by comparison with the reference strain A. xylosoxidans ATCC 27061. The characteristic cellular fatty acids of this species were demonstrated by gas-liquid chromatography. The minimal inhibitory concentrations of 27 antibiotics were determined. The isolates were susceptible to only two: moxalactam at 4 micrograms/ml and ceftazidime at 8 micrograms/ml. The minimal bactericidal concentrations of one disinfectant and three antiseptics were: sodium hypochloride, 109 micrograms/ml; chlorhexidine digluconate in ethanol solution, 15 to 125 micrograms/ml; polyvinylpyrrolidone iodine, 750 micrograms/ml; and iodine ethanol, 312 to 625 micrograms/ml.