Dosing characteristics of oral treprostinil in real-world clinical practice.

Pharmacokinetic studies with oral treprostinil demonstrate that three times daily (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with twice daily (BID) dosing. TID dosing may allow for faster titration, higher total daily doses, and potentially improve the tolerability of oral trepostinil. This analysis, which looks at the real-world dosing of oral treprostinil, supports the utility of TID dosing.

The impact of delayed treatment on 6-minute walk distance test in patients with pulmonary arterial hypertension: A meta-analysis.

BACKGROUND: The impact of treatment delay in stable patients with pulmonary arterial hypertension (PAH) remains unaddressed. METHODS: This meta-analysis included six datasets of PAH therapies with randomized-controlled trials (RCT) and corresponding open-label extension (OLE) studies. We evaluated the change in 6MWD at 1year in the OLE studies by active treatment versus ex-placebo group. The ex-placebo group (i.e., the patients randomized to placebo in the RCT and ultimately treated with active therapy in the OLE) represented the "delay-in-treatment" population. RESULTS: Patients with a treatment delay of 12-16weeks in PAH targeted therapy had an improvement in 6-minute walk distance (6MWD) test at 1year, but this improvement did not amount to the same degree of improvement as their initially treated counterparts. The difference in 6MWD was 15m to 20m at 1year. CONCLUSION: A short-term delay in PAH targeted therapy may adversely affect functional capacity in patients with PAH. This meta-analysis provides some insight as to whether earlier treatment would benefit stable patients with PAH.

Effects of six-week clarithromycin therapy in corticosteroid-dependent asthma: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Although corticosteroids such as prednisone are efficacious for the treatment of severe asthma, chronic administration of oral corticosteroid therapy is associated with significant adverse effects. Previous studies have shown that clarithromycin is effective in reducing bronchial hyperresponsiveness and allergen-induced bronchoconstriction. However, the effect of long-term clarithromycin therapy in patients with prednisone-dependent asthma is uncertain. OBJECTIVE: This study was conducted to determine the effects of oral clarithromycin on prednisone daily dosage, pulmonary function, quality of life (QOL), and asthmatic symptoms in patients with corticosteroid-dependent asthma. METHODS: This 14-week, prospective, randomized, double-blind, placebo-controlled pilot study was conducted at Pulmonary Associates (Phoenix, Arizona) and the University of Illinois at Chicago Medical Center (Chicago, Illinois). Patients aged 18 to 75 years with an established diagnosis of asthma and who had been receiving ≥5 mg/d of prednisone for the preceding 6 months were enrolled. After a 4-week data-collection period, patients received clarithromycin 500 mg BID for 6 weeks, followed by a 4-week follow-up period. The effects of clarithromycin therapy on prednisone dosage requirements, pulmonary function (as assessed using spirometry), QOL, and asthmatic symptoms (nocturnal asthma, shortness of breath, chest discomfort, wheezing, and cough) were assessed. RESULTS: Fourteen patients (9 men, 5 women; mean [SD] age, 62 [13] years) completed the study and were included in the final analysis. One patient withdrew from the study due to clarithromycin-related nausea. After 6 weeks of clarithromycin therapy, patients were able to tolerate a significant reduction in mean (SD) prednisone dosage from baseline (30% [18%]; P- 0.020). Pulmonary function, QOL, and asthmatic symptoms did not significantly worsen despite reduction in prednisone dose. All patients who completed the study tolerated clarithromycin therapy. CONCLUSIONS: In this pilot study of patients with corticosteroid-dependent asthma, 6-week clarithromycin 500 mg BID was clinically effective in allowing a reduction in prednisone dosage, without worsening pulmonary function, QOL, or asthmatic symptoms. In addition, clarithromycin was well tolerated, with only 1 patient discontinuing therapy due to treatment-related nausea.

In vitro bactericidal activity of piperacillin, gentamicin, and metronidazole in a mixed model containing Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis.

An anaerobic, mixed model assay was used to study the bactericidal activities of piperacillin, gentamicin, and metronidazole, alone and in double- and triple-antibiotic combinations against a polymicrobial suspension of E. coli, E. faecalis, and B. fragilis. Only slight differences were noted with the agents when tested against single (10(5) cfu/mL inoculum) versus polymicrobic suspensions (10(6) cfu/mL final inoculum) of susceptible and resistant organisms. Contrary to previous reports in the literature, metronidazole was not active against E. coli in an anaerobic environment (even in the presence of B. fragilis) nor was the activity of metronidazole reduced against B. fragilis in the presence of E. faecalis. Gentamicin demonstrated excellent activity against E. coli when tested in a Bactron anaerobic chamber (5% hydrogen, 5% CO(2,) 90% nitrogen). The pH of the media was only reduced to 6.3-6.7, considerably higher than the pH range of 5-6 needed to significantly reduce the activity of aminoglycosides.

In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas aeruginosa.

The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and ciprofloxacin demonstrated similar in vitro activity, with ofloxacin demonstrating less activity compared to the other agents. Predominantly additive effects were seen with all combinations, with no significant differences detected between the fluoroquinolone agents.