TNF-Receptor Inhibitor Therapy for the Treatment of Children with Idiopathic Pneumonia Syndrome. A Joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521)

AbstractIdiopathic pneumonia syndrome (IPS) is an acute, noninfectious lung disorder associated with high morbidity and mortality after hematopoietic cell transplantation. Previous studies have suggested a role for TNFα in the pathogenesis of IPS. We report a multicenter phase II trial investigating a soluble TNF-binding protein, etanercept (Enbrel, Amgen, Thousand Oaks, CA), for the treatment of pediatric patients with IPS. Eligible patients were < 18 years old, within 120 days after transplantation, and with radiographic evidence of a diffuse pneumonitis. All patients underwent a pretherapy broncho-alveolor lavage (BAL) to establish the diagnosis of IPS. Systemic corticosteroids (2.0 mg/kg/day) plus etanercept (.4 mg/kg twice weekly × 8 doses) were administered. Response was defined as survival and discontinuation of supplemental oxygen support by day 28 of study. Thirty-nine patients (median age, 11 years; range, 1 to 17) were enrolled, with 11 of 39 patients nonevaluable because of identification of pathogens from their pretherapy BAL. In the remaining 28 patients, the median fraction of inspired oxygen at study entry was 45%, with 17 of 28 requiring mechanical ventilation. Complete responses were seen in 20 (71%) patients, with a median time to response of 10 days (range, 1 to 24). Response rates were higher for patients not requiring mechanical ventilation at study entry (100% versus 53%, P = .01). Overall survival at 28 days and 1 year after therapy were 89% (95% confidence interval [CI], 70% to 96%) and 63% (95% CI, 42% to 79%), respectively. Plasma levels of proinflammatory cytokines were significantly increased at onset of therapy, subsequently decreasing in responding patients. The addition of etanercept to high-dose corticosteroids was associated with high response rates and survival in children with IPS

Predictors of Clostridium difficile infection-related mortality among older adults

BACKGROUND: Over 90% of annual deaths caused by Clostridium difficile infection (CDI) occur in persons aged ≥65 years. However, no large-scale studies have been conducted to investigate predictors of CDI-related mortality among older adults. METHODS: This case-control study included 540 CDI patients aged ≥60 years admitted to a tertiary care hospital in Detroit, Michigan, between January 2005 and December 2012. Cases were CDI patients who died within 30 days of CDI date. Controls were CDI patients who survived \u3e30 days after CDI date. Cases were matched to controls on a 1:3 ratio based on age and hospital acquisition of CDI. RESULTS: One-hundred and thirty cases (25%) were compared with 405 controls (75%). Independent predictors of CDI-related mortality included admission from another acute hospital (odds ratio [OR], 8.25; P = .001) or a long-term care facility (OR, 13.12; P = .012), McCabe score ≥2 (OR, 12.19; P \u3c .001), and high serum creatinine (≥1.7 mg/dL) (OR, 3.43; P = .021). The regression model was adjusted for the confounding effect of limited activity of daily living score, total number of antibiotic days prior to CDI, ileus on abdominal radiograph, low albumin (≤2.5 g/dL), elevated white blood cell count (\u3e15 × 1,000/mm3), and admission to intensive care unit because of CDI. CONCLUSIONS: Predictors of CDI-related mortality reported in this study could be applied to the development of a bedside scoring system for older adults with CDI

Trends in Antimicrobial Resistance of Acinetobacter baumannii Isolates from a Metropolitan Detroit Health System ▿

A phenotypic and genotypic analysis of Acinetobacter baumannii was conducted from 2003 to 2008 in Detroit, MI. The incidence of A. baumannii increased from 1.7 to 3.7/1,000 patient days during the study period. Susceptibility to ampicillin-sulbactam and imipenem decreased from ∼90% to ∼40%. Genotyping revealed polyclonality, suggesting either emergence of multiple resistant strains or spread of a common genetic element. The sharp rise mandates major multidisciplinary interventions to optimize management of this multidrug-resistant pathogen