Bleeding events and mortality in SCT patients: a retrospective study of hematopoietic SCT patients with organ dysfunctions due to severe sepsis or GVHD.

In autologous and allogeneic hematopoietic SCT (HSCT) neutropenia may be associated with severe infection. Immunodeficiency associated with GVHD and its treatment in allogeneic HSCT is also a risk for severe infection. In both periods, patients may develop severe sepsis with organ failure. To gain insights into treatment possibilities, HISTORY, a multicenter retrospective study reviewed HSCT patient records on mortality, organ dysfunction, platelet count and bleeding events. All transplantation records from 16 European centers were reviewed for 1.5 years. Of 2092 patients screened, 160 were documented for HSCT with respiratory and/or cardiovascular organ dysfunction because of sepsis and/or GVHD. Mortality was 53.1% at 28 days and 65.6% at 100 days. HSCT patients with sepsis and organ dysfunction are at highest risk of death (49.5%). Death from refractory septic shock was 15.2%, and it was 20% from respiratory failure and 64.7% from sepsis. Fewer than 3% of HSCT patients died from bleeding complications; however, individuals at increased risk of bleeding were excluded. Despite low platelet counts, an increased risk of bleeding could be established only if thrombocytopenia dropped below 13 x 10(9)/l. Thus, there might be a therapeutic window for treatment strategies for severe sepsis in HSCT, such as drotrecogin alpha (activated).

Pulmonary penetration of dirithromycin in patients suffering from acute exacerbation of chronic bronchitis.

The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, dirithromycin regimen. All patients received dirithromycin, 500 mg (two 250 mg tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups (n = 5 in each group) according to sampling time (24, 48, 72, 96 and 120 h, after the last dose). Mean serum concentrations remained low throughout the study (0.44 microgram/ml at 24 h, 0.31 microgram/ml at 48 h, 0.33 microgram/ml at 72 h, 0.12 microgram/ml at 96 h and 0.11 microgram/ml at 120 h, respectively), although they were higher than the MICs for Moraxella catarrhalis for up to 72 h and than that for Streptococcus pneumoniae for up to 120 h after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for S. pneumonia and M. catarrhalis for up to 120 h (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and 0.17 micrograms/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 micrograms/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 micrograms/ml, respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5-day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.

Pharmacokinetics and safety of dirithromycin in the elderly.

Pharmacokinetic and safety studies were undertaken in elderly (age > or = 65 years) and non-elderly (age 18-50 years) subjects receiving the normal recommended dose of 500 mg/day dirithromycin for ten days. There was a considerable variation in the maximum plasma concentration and time when this was achieved in each of the subject groups. There was also a trend for values for the area under the plasma concentration versus time curve to increase with age, but neither of these pharmacokinetic parameters was significantly altered with age. The incidence and nature of adverse events were similar in elderly and non-elderly subjects, and there was no electrocardiographic evidence that dirithromycin caused an increased incidence of cardiac disturbances. No changes in clinical laboratory values were thought to be due to dirithromycin. It is concluded that 500 mg/day dirithromycin may be used to treat elderly patients without the need for any dose adjustment.