Dataset Information

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia.

ABSTRACT: The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration-time curve (AUC) of oral dexamethasone in patients hospitalized with CAP.In this randomized, open label study, 30 patients admitted with CAP were randomized to receive either 4?mg intravenous or 6?mg oral dexamethasone for 4?consecutive days. Serial blood samples were obtained before and after drug administration.Median AUC to infinity was 626??g?l(-1) ?h (IQR 401-1161) for the intravenous group and 774??g?l(-1) ?h (IQR 618-1146) for the oral group. The AUC ratio of 6?mg oral and 4?mg intravenous dexamethasone was 1.22 (95% confidence interval (CI) 0.81, 1.82), which represents a bioavailability of 81% (95% CI 54, 121) after correction for differences in dexamethasone dose.Bioavailability of oral dexamethasone in patients hospitalized with pneumonia is sufficient. This makes oral dexamethasone an appropriate alternative for intravenous administration in these patients.

SUBMITTER: Spoorenberg SM

PROVIDER: S-EPMC4168382 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia.

Spoorenberg Simone M C SM Deneer Vera H M VH Grutters Jan C JC Pulles Astrid E AE Voorn G P Paul GP Rijkers Ger T GT Bos Willem Jan W WJ van de Garde Ewoudt M W EM

British journal of clinical pharmacology 20140701 1

<h4>Aim</h4>The use of corticosteroids as adjunctive therapy might be effective in patients with community-acquired pneumonia (CAP). Oral administration of dexamethasone is a practical and safer alternative to the intravenous route. Since patients hospitalized with pneumonia might have delayed gastric emptying, this study explored systemic exposure in terms of area under the concentration-time curve (AUC) of oral dexamethasone in patients hospitalized with CAP.<h4>Methods</h4>In this randomized, ...[more]

PMID: 24400953

Similar Datasets

Project description:BackgroundThe most frequently prescribed regimens for the treatment of hospitalized adults with suspected or documented community-acquired bacterial pneumonia (CABP), an acute bacterial infection of the pulmonary parenchyma, are ceftriaxone plus a macrolide, or a respiratory fluoroquinolone. Although these regimens are consistent with expert guidelines, there are growing concerns regarding their safety and efficacy. Omadacycline is a once-daily antibiotic with oral and intravenous (IV) formulations; it was recently approved in the United States for the treatment of adults with CABP.ObjectiveTo estimate the cost impact of shortening hospital stay or avoiding hospitalization when using a treatment with an IV and an oral formulation, such as omadacycline, versus an IV-only drug regimen, such as ceftriaxone plus a macrolide, in adults with CABP who are not candidates for respiratory fluoroquinolone therapy.MethodsWe developed 2 conceptual healthcare decision models to identify potential cost-saving opportunities in hospitalized adults with CABP who receive omadacycline versus ceftriaxone plus a macrolide. The early hospital discharge model examined the cost impact of shifting patients with CABP from inpatient treatment with ceftriaxone plus a macrolide to inpatient IV omadacycline treatment and early hospital discharge with oral omadacycline. The hospital-avoidance model examined the cost impact of omadacycline treatment in the outpatient setting in patients with CABP who have low disease severity. The models defined the upper range of the daily acquisition cost for omadacycline that conferred cost-savings relative to inpatient treatment with ceftriaxone plus a macrolide.ResultsIn the early hospital discharge model, omadacycline showed cost-savings with a 2-day hospital stay reduction if the daily cost of omadacycline was ?$836, almost twice its wholesale acquisition cost. In the hospital-avoidance model, the daily omadacycline thresholds that still conferred cost-savings relative to inpatient ceftriaxone plus a macrolide ranged from $1302 to $1334, based on a daily wholesale acquisition cost of $450 for omadacycline, depending on the potential use of the emergency department and an observation unit.ConclusionThe study findings show that the targeted use of omadacycline for the treatment of select patient populations with CABP could result in cost-savings relative to inpatient treatment with ceftriaxone plus a macrolide.

Project description:BACKGROUND:Empirical antibiotic coverage for atypical pathogens in community-acquired pneumonia (CAP) has long been debated, mainly because of a lack of epidemiological data. We aimed to assess both testing for atypical pathogens and their prevalence in hospitalized patients with CAP worldwide, especially in relation with disease severity. METHODS:A secondary analysis of the GLIMP database, an international, multicentre, point-prevalence study of adult patients admitted for CAP in 222 hospitals across 6 continents in 2015, was performed. The study evaluated frequency of testing for atypical pathogens, including L. pneumophila, M. pneumoniae, C. pneumoniae, and their prevalence. Risk factors for testing and prevalence for atypical pathogens were assessed through univariate analysis. RESULTS:Among 3702 CAP patients 1250 (33.8%) underwent at least one test for atypical pathogens. Testing varies greatly among countries and its frequency was higher in Europe than elsewhere (46.0% vs. 12.7%, respectively, p?<?0.0001). Detection of L. pneumophila urinary antigen was the most common test performed worldwide (32.0%). Patients with severe CAP were less likely to be tested for both atypical pathogens considered together (30.5% vs. 35.0%, p?=?0.009) and specifically for legionellosis (28.3% vs. 33.5%, p?=?0.003) than the rest of the population. Similarly, L. pneumophila testing was lower in ICU patients. At least one atypical pathogen was isolated in 62 patients (4.7%), including M. pneumoniae (26/251 patients, 10.3%), L. pneumophila (30/1186 patients, 2.5%), and C. pneumoniae (8/228 patients, 3.5%). Patients with CAP due to atypical pathogens were significantly younger, showed less cardiovascular, renal, and metabolic comorbidities in comparison to adult patients hospitalized due to non-atypical pathogen CAP. CONCLUSIONS:Testing for atypical pathogens in patients admitted for CAP in poorly standardized in real life and does not mirror atypical prevalence in different settings. Further evidence on the impact of atypical pathogens, expecially in the low-income countries, is needed to guidelines implementation.

Project description:Community acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.PROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.With the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.The PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Dataset Information

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia.

Publications

Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets