Pharmacokinetics of ciprofloxacin and its penetration into bronchial secretions of mechanically ventilated patients with chronic obstructive pulmonary disease

We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (C(max)) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC(0-24)) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a mean C(max) of 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC(0-24)/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 μg/ml, respectively. Slightly better results were obtained for the ratio C(max)/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 μg/ml.     

Tuberculosis in patients with systemic rheumatic or pulmonary diseases treated with glucocorticosteroids and the preventive role of isoniazid: a review of the available evidence

Development of tuberculosis (TB) is a concern in patients who receive glucocorticosteroids for the treatment of chronic rheumatic or pulmonary diseases. However, the incidence of development of TB in such patients and the prophylactic role of isoniazid (INH) are unclear. We evaluated the available evidence from 20 relevant prospective and retrospective cohort and case–control studies identified in the PubMed and Cochrane databases. The frequency of development of TB in the populations studied varied from 0% to 13.8%. This figure was low in studies performed in countries with a low incidence of TB (0% in the USA and Greece, 0.6% in France and 1.35% in Spain). In contrast, the frequency of development of TB in the studied cohorts was high in studies performed in countries with a moderate to high incidence of TB (from 2.5% in South Korea to 13.8% in The Philippines). Isoniazid prophylaxis (INHP) was found to decrease the incidence of development of TB in two of four studies that examined this intervention. The available evidence suggests that patients who receive steroids for the treatment of chronic rheumatic or pulmonary diseases and who live in countries with a high incidence of TB have a high risk of development of TB in contrast to patients who live in countries with a low incidence of the infection. However, the role of INHP even for patients living in countries where TB is endemic is unclear because the effectiveness of INH in preventing TB development in such patients is not well established and there are cost-effectiveness and safety issues.     

Sildenafil combined with continuous positive airway pressure for treatment of erectile dysfunction in men with obstructive sleep apnea

Objectives To assess efficacy and safety of the combination of sildenafil and continuous positive airway pressure (CPAP), and satisfaction with treatment for erectile dysfunction (ED) in men with obstructive sleep apnea (OSA). Patients and methods Forty men suffering from OSA and concurrent ED were treated with CPAP after a thorough investigation. After a 4-week run-in period, the patients were randomly allocated to treatment for 6 weeks; 20 men to the combination group, receiving additionally 100 mg sildenafil on demand for intercourse, and 20 men to CPAP alone. After a 1-week washout phase, the two groups switched to the other treatment arm for an additional 6 weeks period. End points for efficacy evaluation were the percentage of successful attempts for intercourse based on an event log and the overall satisfaction with sildenafil in the treatment of ED. Results The patients recorded a total of 149 attempts for intercourse during the run-in phase with a success rate of 19.5%. During the 12 weeks of treatment, the success rate of intercourse attempts was 24.8% when only on CPAP and 61.1% when in combination with sildenafil (P < 0.001). Of the studied men, 70% were satisfied with the use of sildenafil while 30% remained unhappy with this additional treatment. Conclusions Sildenafil in combination with CPAP appears clearly superior to CPAP alone. The efficacy of this combination is superior to that of sildenafil alone, as reported in previous studies. Both treatment modalities are safe and well tolerated. However, approximately one-third of the patients remain unsatisfied even from the␣combination treatment. Further treatment options are needed.     

Predictors of all-cause mortality for patients with Chagas' cardiomyopathy listed for heart transplantation

This study sought to determine independent predictors of all-cause mortality for patients with Chagas' disease heart failure listed for heart transplantation. Need of inotropic support (p=0.01; hazard ratio=14.68, 95% Confidence Interval 1.86 to 115.82) and the Transpulmonary Gradient (p=0.02; HR=1.15, 95% Confidence Interval 1.03 to 1.30) were established independent predictors of all-cause mortality.     

No significant improvement in the outcome of patients with Waldenström's macroglobulinemia treated over the last 25 years

The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2‐microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent‐based regimens and most patients who started treatment after January 1, 2000 received rituximab‐based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high‐risk disease. Possible differences in the 15‐ or 20‐year survival rate between the two groups may be detected with further follow‐up of these patients. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.