A pooled analysis of patients with wound infections in the Phase 3 REVIVE trials: randomized, double-blind studies to evaluate the safety and efficacy of iclaprim versus vancomycin for treatment of acute bacterial skin and skin structure infections.

Introduction. Iclaprim is a diaminopyrimidine antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to Gram-positive pathogens.Aim. This analysis evaluates patients with wound infections from two Phase 3 trials of ABSSSI.Methodology. Six-hundred-two patients with wound infections from two Phase 3, double-blinded, randomized, multicenter, active controlled trials (REVIVE-1/-2) were evaluated in a post hoc analysis of iclaprim 80 mg compared with vancomycin 15 mg kg-1 administered intravenously every 12 h for 5-14 days. The primary endpoint was to determine whether iclaprim was non-inferior (10 % margin) to vancomycin in achieving a ≥20 % reduction from baseline in lesion size 48-72 h after starting study drug (early clinical response [ECR]). Safety was assessed.Results. In REVIVE-1, ECR was 83.5 % with iclaprim versus 79.7 % with vancomycin (treatment difference 3.77%, 95 % CI -4.50%, 12.04%). In REVIVE-2, ECR was 82.7 % with iclaprim versus 76.3 % with vancomycin (treatment difference 6.38%, 95 % CI -3.35%, 16.12%). In the pooled dataset, iclaprim had similar ECR rates compared with vancomycin among wound infection patients (83.2 % vs 78.2 %) with a treatment difference of 5.01 % (95 % CI -1.29%, 11.32%). The safety profile was similar in iclaprim- and vancomycin-treated patients, except for a higher incidence of diarrhea with vancomycin (n=17) compared with iclaprim (n=6) and fatigue with iclaprim (n=17) compared with vancomycin (n=8).Conclusion. Based on early clinical response, iclaprim achieved non-inferiority to vancomycin with a similar safety profile in patients with wound infections suspected or confirmed as caused by Gram-positive pathogens. Iclaprim may be a valuable treatment option for wound infections.

A Pooled Analysis of the Safety and Efficacy of Iclaprim Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Patients With Intravenous Drug Use: Phase 3 REVIVE Studies.

PURPOSE: This analysis evaluates the efficacy and safety of iclaprim versus vancomycin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in patients who were intravenous drug users (IVDUs). METHODS: A total of 621 patients who were IVDUs from 2 parallel Phase III, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2) were analyzed separately and pooled. This post hoc analysis summarizes the efficacy and safety profile of iclaprim 80 mg fixed dose compared with vancomycin 15 mg/kg administered intravenously during 2 h every 12 h for 5-14 days among this population. The primary end point of these studies was to determine whether iclaprim was noninferior (10% margin) to vancomycin in achieving a ≥20% reduction in lesion size at 48-72 h after initiation of treatment with the study drug (early clinical response) in the intent-to-treat population. The safety profile was assessed based on adverse events and laboratory parameters. FINDINGS: Iclaprim had higher early clinical response rates (85.8%; 95% CI, 81.5%-89.4%) compared with vancomycin (79.8%; 95% CI, 74.8%-84.2%) among patients with ABSSSIs who were IVDUs, with a treatment difference of +6.00% (95% CI, 0.06-12.0). The safety profile was similar in the iclaprim and vancomycin arms, with 3.7% and 5.0%, respectively, of patients discontinuing study therapy because of adverse events and 1.9% and 3.4%, respectively, of patients developing serious adverse events. IMPLICATIONS: Iclaprim had a higher early clinical response rate and favorable safety profile compared with vancomycin for the treatment of ABSSSIs in patients who were IVDUs. Iclaprim may be a valuable treatment option for ABSSSIs in this patient population.

Alcohol consumption and risk of ischemic stroke: The Framingham Study.

BACKGROUND AND PURPOSE: Stroke is a major cause of death in the United States. The association between alcohol consumption and ischemic stroke (IS) remains controversial. METHODS: We used data collected on participants in the Framingham Study to assess the association between total alcohol intake and type of alcoholic beverage and development of IS, overall and according to age. RESULTS: A total of 196 men and 245 women developed IS during three 10-year follow-up periods. In the categories of never drinkers, drinkers of 0.1 to 11, 12 to 23, and > or =24 g/d of ethanol (a "typical drink" is approximately 12 g of ethanol), and former drinkers of 0.1 to 11 and > or =12 g/d, crude incidence rates of IS were 6.5, 5.9, 4.9, 5.0, 6.7, and 17.8 cases per 1000 person-years, respectively, for men and 5.9, 4.1, 4.1, 4.3, 8.3, and 7.1, respectively, for women. Overall, compared with never drinkers in a multivariate Cox regression, current alcohol consumption was not related significantly to IS in either sex. Former drinking of > or =12 g/d of alcohol was associated with a 2.4 times higher risk of IS among men but not among women. When stratified by age, alcohol intake was associated with lower risk of IS among subjects aged 60 to 69 years. In beverage-specific analysis, only wine consumption was related to a decreased risk of IS. CONCLUSIONS: Our data showed no significant association between total alcohol and IS overall but showed a protective effect of alcohol among subjects aged 60 to 69 years.

The influence of gender and age on disability following ischemic stroke: the Framingham study.

The magnitude of disability among elderly stroke survivors is substantial. There have been few community-based estimates of the contribution gender and older age make to stroke-related disability and outcome. Using the original Framingham Study cohort, we documented gender-specific neurological deficits and disability differences in stroke survivors at six months post-stroke. Logistic regression analyses were performed to estimate odds ratios, comparing men and women, and adjusting for age, and age and stroke subtype. Age and gender-matched controls were then compared to distinguish stroke-related disability from disability associated with general aging. Results showed that almost half (43%) of all elderly stroke survivors in the cohort had moderate to severe neurological deficits. In the crude analyses, women were more dependent in ADLs (33.9% vs 15.6%), less likely to walk unassisted (40.3% vs 17.8%), and living in nursing homes (34.9 % vs 13.3%). After adjusting for age and stroke subtype, it was older age that accounted for the severity of disability. When compared to age and gender-matched controls, stroke cases were significantly more disabled in all domains studied. In this elderly cohort, more women experienced initial strokes and were more disabled at 6 months post-stroke than men. However, older age at stroke onset, not gender or stroke subtype, was associated with greater disability. Health care providers need to understand that strokes occur later in life for women and that because of age, women are at greater risk for disability and institutionalization.