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Clinical analysis of pulmonary infection in hemodialysis patients.

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The present study aimed to investigate the pathogen distribution and drug resistance of lung infections in hemodialysis to guide clinical empirical pharmacy. The clinical data of 116 hemodialysis patients with pulmonary infection were analyzed. The majority of the 82 pathogens isolated from the sputa of patients were Gram-negative bacteria (accounting for 71.95%).

The results of the drug sensitivity test suggested that Gram-negative bacilli had low resistance rates to piperacillin and tazobactam, imipenem and amikacin, while Gram-positive cocci had a low resistance rate to vancomycin. All resistance rates of the pathogens to other common antimicrobials were >50%. The pathogens resulting in lung infections in hemodialysis patients were mainly Gram-negative bacteria and were significantly resistant to various antibacterials.

Results of the this study demonstrate that pathological examination should be performed as early as possible and effective antimicrobial agents should be chosen according to drug sensitivity test results.

Pulmonary penetration of piperacillin and tazobactam in critically ill patients.

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Pulmonary infections in critically ill patients are common and associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target site antibiotic concentrations in patients with pneumonia.

The aim of this study was to assess the plasma and intra-pulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intra-pulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic endpoints and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored.

The median piperacillin and tazobactam pulmonary penetration ratio was 49.3% and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentration were unpredictable and negatively correlated to pulmonary permeability.

Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam susceptible organisms in some critically ill patients.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 13 June 2014; doi:10.1038/clpt.2014.131.

The role of macrolides in asthma: current evidence and future directions.

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Macrolides, such as clarithromycin and azithromycin, possess antimicrobial, immunomodulatory, and potential antiviral properties. They represent a potential therapeutic option for asthma, a chronic inflammatory disorder characterised by airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing.

Results from clinical trials, however, have been contentious. The findings could be confounded by many factors, including the heterogeneity of asthma, treatment duration, dose, and differing outcome measures. Recent evidence suggests improved effectiveness of macrolides in patients with sub-optimally controlled severe neutrophilic asthma and in asthma exacerbations. We examine the evidence from clinical trials and discuss macrolide properties and their relevance to the pathophysiology of asthma. At present, the use of macrolides in chronic asthma or acute exacerbations is not justified. Further work, including proteomic, genomic, and microbiome studies, will advance our knowledge of asthma phenotypes, and help to identify a macrolide-responsive subgroup.

Future clinical trials should target this subgroup and place emphasis on clinically relevant outcomes such as asthma exacerbations.

Percutaneous microwave ablation of stage I medically inoperable non-small cell lung cancer: Clinical evaluation of 47 cases.

MWATo retrospectively evaluate safety and effectiveness of CT-guided percutaneous microwave ablation (MWA) in 47 patients with medically inoperable stage I peripheral non-small cell lung cancer (NSCLC).

METHODS: From February 2008 to October 2012, 47 patients with stage I medically inoperable NSCLC were treated in 47 MWA sessions. The clinical outcomes were evaluated. Complications after MWA were also summarized.

RESULTS: At a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, 5 years after MWA were 96%, 64%, and 48%, respectively. The median cancer-specific and median overall survivals were 47.4 and 33.8 months. The overall survival rates at 1, 2, 3, and 5 years after MWA were 89%, 63%, 43%, and 16%, respectively. Tumors ≤3.5 cm were associated with better survival than were tumors >3.5 cm. The complications after MWA included pneumothorax (63.8%), hemoptysis (31.9%), pleural effusion (34%), pulmonary infection (14.9%), and bronchopleural fistula (2.1%).

CONCLUSIONS: MWA is safe and effective for the treatment of medically inoperable stage I peripheral NSCLC. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.

Population Pharmacokinetics of Inhaled Umeclidinium and Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

A fixed-dose combination of the bronchodilators umeclidinium and vilanterol is in development for the long-term, once-daily treatment of chronic obstructive pulmonary disease (COPD). We characterized the pharmacokinetics of umeclidinium and vilanterol in ≈1,635 patients with COPD, evaluating the impact of patient demographics and baseline characteristics on umeclidinium and vilanterol exposure.

Methods : Plasma concentrations of umeclidinium and vilanterol were evaluated in patients enrolled in two phase III, randomized, double-blind, parallel-group, placebo-controlled trials using inhaled umeclidinium/vilanterol combination therapy and inhaled umeclidinium and vilanterol monotherapies as treatments. Population-pharmacokinetic models were developed using non-linear mixed-effects analyses, performed using NONMEM® software. A likelihood-based approach was used to characterize the data below limit of quantification. Umeclidinium and vilanterol exposures at clinical doses were simulated based on the population model.

Results : For the umeclidinium and vilanterol population-pharmacokinetic analyses, 1,635 and 1,637 patients provided 8,498 and 8,405 observations, respectively. Umeclidinium and vilanterol pharmacokinetics were best described by a two-compartment model with first-order absorption. For umeclidinium, bodyweight, age, and creatinine clearance (CLCR) were statistically significant covariates for apparent inhaled clearance (CL/F);bodyweight was a statistically significant covariate for volume of distribution of central compartment (V 2/F).The population parameter estimates namely CL/F and V 2/F for umeclidinium were 218 L/h and 1,160 L and 40.9 L/h and 268 L for vilanterol.

For vilanterol, bodyweight and age were statistically significant covariates for CL/F. The effect of covariates on umeclidinium and vilanterol systemic exposure was marginal. The population model indicates that a 10 % increase in bodyweight will result in a 2 % increase in CL/F for umeclidinium and vilanterol and 6 % increase in umeclidinium V 2/F. A 10 % increase in age will provide a 7 and 4 % decrease in umeclidinium and vilanterol CL/F, respectively. A 10 % decrease in CLCR will result in a 3 % decrease in umeclidinium CL/F. Umeclidinium and vilanterol population-pharmacokinetic model-based systemic exposure predictions showed no pharmacokinetic interactions between umeclidinium and vilanterol when administered in combination.

Conclusions : There were no apparent pharmacokinetic interactions when umeclidinium and vilanterol were co-administered in patients with COPD. The effects of patient demographics, including age, bodyweight, and CLCR, on umeclidinium or vilanterol systemic exposure were minimal, and therefore no dose adjustments are necessary.

 

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