u-62840 and Bacterial-Infections

Long-term intravenous infusion of epoprostenol and treprostinil for treatment of pulmonary arterial hypertension (PAH) via a central venous catheter is associated with the risk of bloodstream infection (BSI). While several potential explanations exist for possible differences in BSI incidence among intravenous prostanoids, one hypothesis suggests that the alkaline pH of epoprostenol in Sterile Diluent for Flolan (SDF) has greater antimicrobial activity compared with the neutral pH of other common diluents such as sterile saline or water, which have been used for treprostinil.. The chemical stability and antimicrobial activity of 4 microg/ml and 130 microg/ml treprostinil in SDF were assessed according to United States and European Pharmacopeia.. At both concentrations, treprostinil in SDF remained stable after incubation at 40 degrees C and ambient relative humidity for up to 52 h. Solution pH also remained stable (range 10.4-10.6), and the solutions were essentially free of particulate at all time points examined. Antimicrobial activity was measured using an antimicrobial effectiveness test after inoculation with five species of bacteria, yeast and mould. The antimicrobial activity of both concentrations of treprostinil met United States Pharmacopeia requirements. Further, the antimicrobial activity of treprostinil in SDF against gram-negative bacteria (> 4 log(10) reductions) exceeded that previously described for treprostinil in sterile saline.. These results suggest that dilution of treprostinil with the alkaline solution SDF may reduce the risk of infection from inadvertent patient contamination compared with dilution of treprostinil in sterile saline.

Topics: Anti-Infective Agents; Antihypertensive Agents; Bacteria; Bacterial Infections; Catheterization, Central Venous; Drug Stability; Epoprostenol; Equipment Contamination; Fungi; Humans; Infusions, Intravenous; Mycoses; Sodium Chloride; Time Factors; Water

Treatment of arterial pulmonary hypertension with epoprostenol (intravenous prostacyclin) improves survival and quality of life, but the need for an implanted central venous catheter is associated with frequent complications, that often (as in the case of infection or dislodgment) are serious and require catheter replacement. Treprostinil is a prostacyclin analogue suitable for continuous subcutaneous administration. We report the successful transition from intravenous epoprostenol to subcutaneuos treprostinil in four patients with severe pulmonary hypertension who suffered from serious complications associated with the epoprostenol infusion system.

Topics: Adult; Antihypertensive Agents; Bacterial Infections; Catheterization, Central Venous; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Injections, Subcutaneous; Middle Aged