Tula Virus as Causative Agent of Hantavirus Disease in Immunocompetent Person,Germany

We report molecular evidence of Tula virus infection in an immunocompetent patient from Germany who had typical signs of hantavirus disease. Accumulating evidence indicates that Tula virus infection, although often considered nonpathogenic, represents a threat to human health.     

Prevalence of nosocomial infections in Swiss children's hospitals.

OBJECTIVE: To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. DESIGN: Prevalence survey and evaluation of a new comorbidity index. SETTING: Seven Swiss pediatric hospitals. PATIENTS: Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. RESULTS: Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS: This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospitals.     

Isoniazid Mediates the CYP2B6*6 Genotype-Dependent Interaction between Efavirenz and Antituberculosis Drug Therapy through Mechanism-Based Inactivation of CYP2A6

Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations in patients with the CYP2B6*6/*6 genotype (but not the CYP2B6*1/*1 genotype) during coadministration with the commonly used four-drug antituberculosis therapy. This study sought to elucidate the mechanism underlying this genotype-dependent drug-drug interaction. In vitro studies were conducted to determine whether one or more of the antituberculosis drugs (rifampin, isoniazid, pyrazinamide, or ethambutol) potently inhibit efavirenz 8-hydroxylation by CYP2B6 or efavirenz 7-hydroxylation by CYP2A6, the main mechanisms of efavirenz clearance. Time- and concentration-dependent kinetics of inhibition by the antituberculosis drugs were determined using genotyped human liver microsomes (HLMs) and recombinant CYP2A6, CYP2B6.1, and CYP2B6.6 enzymes. Although none of the antituberculosis drugs evaluated at up to 10 times clinical plasma concentrations were found to inhibit efavirenz 8-hydroxylation by HLMs, both rifampin (apparent inhibition constant [K_i] = 368 μM) and pyrazinamide (K_i = 637 μM) showed relatively weak inhibition of efavirenz 7-hydroxylation. Importantly, isoniazid demonstrated potent time-dependent inhibition of efavirenz 7-hydroxylation in both HLMs (inhibitor concentration required for half-maximal inactivation [K_I] = 30 μM; maximal rate constant of inactivation [k_inact] = 0.023 min⁻¹) and recombinant CYP2A6 (K_I = 15 μM; k_inact = 0.024 min⁻¹) and also formed a metabolite intermediate complex consistent with mechanism-based inhibition. Selective inhibition of the CYP2B6.6 allozyme could not be demonstrated for any of the antituberculosis drugs using either recombinant enzymes or CYP2B6*6 genotype HLMs. In conclusion, the results of this study identify isoniazid as the most likely perpetrator of this clinically important drug-drug interaction through mechanism-based inactivation of CYP2A6.     

Das Modellprojekt ReWiKs

Several studies point to various barriers in achieving sexual self-determination for people with disabilities as well as a high degree of thematic uncertainty among staff in residential homes. In addition, women with disabilities and people in institutions are especially at risk in a particular way, to be victims of sexual violence. The ReWiKs project develops, based on evaluated guidelines for sexual self-determination, materials in order to reflect the institutional handling of the subject. Training modules and recommendations are also developed. In addition, extracts of materials are created in simple language. All materials are evaluated before their publication in an intensive theory-practice dialogue.