The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 ...countries worldwide, involved patients with complicated skin and skin-structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, ⩽2 µg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated skin and skin-structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated skin and skin-structure infections or complicated intra-abdominal infections.
Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an ...effective maintenance therapy for patients with fistulas.
We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization.
The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009).
Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.
A series of conformationally constrained bicyclic derivatives derived from SR141716 was prepared and evaluated as hCB
1-R antagonists and inverse agonists. Optimization of the structure–activity ...relationships around the 2,6-dihydro-pyrazolo4,3-
dpyrimidin-7-one derivative
2a led to the identification of two compounds with oral activity in rodent feeding models (
2h and
4a). Replacement of the PP group in
2h with other bicyclic groups resulted in a loss of binding affinity.
Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a ...prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was ⩾0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection.
A study of Sitka spruce plantations of varying age on stagnopodsols in Wales has shown that relatively little nitrate leaches from forests of under 30 years, but it does so to a statistically ...significant and increasing extent from older forests. It has been hypothesised that P and K deficiencies develop in later stages of the forest rotation which effectively limit N demand by the trees resulting in nitrate leaching. To test this hypothesis, bioassays to determine tree nutrient demands relative to supply, based on rates of uptake of isotopically labelled ions (
32P,
86Rb and
15N) by live roots were applied to four stands on stagnopodsol soils in each of five Welsh forests (Beddgelert, Dyfi, Dyfnant, Hafren and Tywi). Older forest sites where stream nitrate concentrations were generally over 0.16 mg N 1
−1 tended to have a higher demand for P and K, but a low demand for N, indicating that nitrate leaching may be associated with deficiencies in supply of P and K. Multivariate analysis of root bioassay data showed that sites leaching nitrate could be distinguished at
P < 0.01 from those not leaching nitrate. The critical load for pollutant N inputs to the Welsh forests will therefore need to be calculated using the mass balance equation modified to take account of P and K deficiencies on certain soil types.
A pilot study to test the effectiveness of medication instruction was carried out using 61 voluntary participants age 65 and older. They were interviewed regarding their medication taking, and ...instruction was individualized using one of four teaching modes: oral; written; oral and written; and oral and written combined with memory aids. Postinstruction interviews revealed no significant difference in compliance among all groups. The preinstruction mean compliance score of all subjects was 98.8 percent. Although compliance, judged specifically on the basis of the prescription label instructions, was extremely high both before and after instruction, drug-taking behavior and knowledge did change. The preinstruction compliance score does not necessarily reflect safe or desirable drug-taking behavior. There was no specific information given to clients with their prescriptions and prescription medications, indicating, for drug-therapy decision makers, a much broader problem than non-compliance.
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