Long-Term Safety and Efficacy Data of a Plasma-Derived Factor VIII Concentrate with von Willebrand Factor for Treatment of Patients with Hemophilia A Covering 18 Years.

We describe the results of the (to our knowledge) longest long-term noninterventional study so far performed to obtain real-life data on the treatment of hemophilia A patients with a single plasma-derived FVIII concentrate containing von Willebrand factor (pdFVIII; Haemoctin/Faktor VIII SDH Intersero). A total of 198 patients (146 in Germany and 52 in Hungary), of whom 160 had severe and 38 nonsevere hemophilia A, representing all age groups (0-88 years; mean ∼25 years at inclusion) were analyzed during prophylactic or on-demand treatment over 18 years (overall 1,418 patient-years; mean >7 years). pdFVIII was very effective and well tolerated. The mean annual bleeding rate, including spontaneous and traumatic bleeds, was considerably lower for patients treated prophylactically (mean 5.4; median 3.1) than for patients treated on demand (mean 26.1; median 21.9). Inhibitors were found in 13% (3/23) and high-titer inhibitors in 4% (1/23) of previously untreated patients with severe hemophilia A. Four previously treated patients with severe hemophilia A developed inhibitors, thereof three high-titer inhibitors (3.3 and 2.5 high-titer inhibitors in 1,000 patient-years). No unexpected adverse effect on the health of the patients, no pdFVIII-related thrombosis, thromboembolic event, or hypersensitivity reaction, and no suspected viral transmission related to pdFVIII were documented.

Time trend of prevalence and susceptibility to nitrofurantoin of urinary MDR Escherichia coli from outpatients.

OBJECTIVES: To assess the time trend of the prevalence of urinary MDR Escherichia coli in Belgian outpatients (2005 versus 2011-12), the antibiotic susceptibility of urinary MDR E. coli, and the time trend of non-susceptibility to nitrofurantoin, i.e. first-line treatment for uncomplicated urinary tract infections (UTIs), of urinary MDR E. coli (2005 versus 2011-12). METHODS: In this secondary analysis of a multicentre study, which collected a convenience sample of voluntary participating laboratories (15 and 8 in 2005 and 2011-12, respectively), we analysed antimicrobial susceptibilities (ampicillin, amoxicillin/clavulanate, cefalotin, ciprofloxacin, nitrofurantoin and trimethoprim/sulfamethoxazole) of urinary E. coli. MDR was defined as resistance to three or more of these agents. The prevalence of MDR E. coli and its non-susceptibility to nitrofurantoin was compared between 2005 and 2011-12 using a generalized estimating equation model. RESULTS: MDR status could be determined for 9704 and 12512 urinary E. coli isolates from 7911 and 9441 patients in 2005 and 2011-12, respectively, with most patients being women (79% in both study periods). The prevalence of MDR increased from 28.4% (2758/9704) in 2005 to 34.3% (4286/12512) in 2011-12 (adjusted OR 1.305; 95% CI 1.220-1.397). Within the MDR isolates, the prevalence of nitrofurantoin non-susceptibility decreased from 23.2% (623/2684) in 2005 to 10.7% (455/4253) in 2011-12 (adjusted OR 0.424; 95% CI 0.363-0.494). CONCLUSIONS: Despite a high prevalence of MDR E. coli in urinary samples from Belgian outpatients, nitrofurantoin could still be recommended as first-line empirical treatment in uncomplicated UTIs.

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.