Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]

INTRODUCTION: PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care). METHODS: Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism. RESULTS: Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin–antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days. CONCLUSION: Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups

Risk-benefit analysis for drotrecogin alfa (activated)

An analysis of risks and benefits is an important component of patient care. Drotrecogin alfa (activated), the first approved cogin (a class of recombinant human coagulation inhibitors), provides a clear example of a treatment that requires a careful risk-benefit analysis. Treatment with this novel compound has been shown to reduce significantly the risk of death in patients with sepsis and acute organ dysfunction (severe sepsis). However, the drug is a natural antithrombotic that can increase the risk of bleeding in recipients. We will discuss bleeding and other potential risks associated with drotrecogin alfa (activated) treatment, as well as the survival benefits seen with the use of this therapy in patients with severe sepsis

Prosthetic valve endocarditis caused by Candida lusitaniae, an uncommon pathogen: a case report

© 2009 Michel et al; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Multicenter, Open-Label, Randomized Comparison of Levofloxacin and Azithromycin Plus Ceftriaxone in Hospitalized Adults with Moderate to Severe Community-Acquired Pneumonia

Abstract Background: Changing etiologic patterns and the growing problem of antimicrobial resistance, particularly an increase in macrolide-resistant pneumococcal bacteremia, are causing physicians to adopt new approaches to the treatment of community-acquired pneumonia (CAP). Objective: The relative efficacy and tolerability of levofloxacin monotherapy and azithromycin and ceftriaxone combination therapy were assessed in hospitalized adults with moderate to severe CAP. Methods: This Phase IV, multicenter, open-label, randomized trial compared 2 treatment regimens: (1) levofloxacin 500 mg PO or IV q24h, and (2) azithromycin 500 mg IV q24h for ≥2 days plus ceftriaxone 1 g IV q24h for 2 days, followed by an optional transition to azithromycin 500 mg PO q24h at the investigator’s discretion. The total duration of therapy was to be a minimum of 10 days in both treatment groups. Ceftriaxone was included in the initial azithromycin regimen to ensure coverage against pneumococcal bacteremia. Results: Of 236 patients in the intent-to-treat population, completion or withdrawal information was available for 110 patients in the levofloxacin group and 114 in the azithromycin group. Baseline demographic and disease characteristics were comparable between groups. At the end of treatment, the clinical success rate (cured + improved) in clinically evaluable patients was 94.1% in the levofloxacin group and 92.3% in the azithromycin group. The respective posttherapy microbiologic eradication rates were 89.5% and 92.3%. Levofloxacin was as well tolerated as azithromycin, with an incidence of drug-related adverse events (AEs) for all body systems of 5.3% and 9.3%, respectively. One patient receiving levofloxacin had a serious drug-related AE, compared with 7 patients receiving azithromycin. Conclusions: In this study in hospitalized patients with moderate to severe CAP, levofloxacin monotherapy was at least as effective as a combination regimen of azithromycin and ceftriaxone in providing coverage against the current causative pathogens in CAP. In addition, levofloxacin was as well tolerated as the combination of azithromycin and ceftriaxone

Clinical Study Bronchial Responsiveness in Patients with Restrictive Spirometry

Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defined as a decreased FVC and FEV1, with normal FEV1/FVC. Responsiveness to bronchodilators was defined as an improvement in FEV1 and/or FVC of at least 12% and 200 mL. Patients with lung volume measurements had their clinical and radiographic records reviewed. Results. Twenty-one patients were included in the study. Most were current or ex-smokers, with most being on bronchodilators. The average FVC and FEV1 were 65 ± 11% and 62 ± 10% of the predicted, respectively. Most patients (66%) had a normal TLC, averaging 90 ± 16% of the predicted. RV, RV/TLC, and the TLC-VA values strongly suggested an obstructive defect. Conclusions. Reversible restrictive pattern on spirometry appears to be a variant of obstructive lung disease in which early airway closure results in air trapping and low FVC. In symptomatic patients, a therapeutic trial of bronchodilators may be beneficial

Bronchial Responsiveness in Patients with Restrictive Spirometry

Background. Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. Methods. Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defined as a decreased FVC and FEV1, with normal FEV1/FVC. Responsiveness to bronchodilators was defined as an improvement in FEV1 and/or FVC of at least 12% and 200 mL. Patients with lung volume measurements had their clinical and radiographic records reviewed. Results. Twenty-one patients were included in the study. Most were current or ex-smokers, with most being on bronchodilators. The average FVC and FEV1 were 65±11% and 62±10% of the predicted, respectively. Most patients (66%) had a normal TLC, averaging 90±16% of the predicted. RV, RV/TLC, and the TLC-VA values strongly suggested an obstructive defect. Conclusions. Reversible restrictive pattern on spirometry appears to be a variant of obstructive lung disease in which early airway closure results in air trapping and low FVC. In symptomatic patients, a therapeutic trial of bronchodilators may be beneficial

Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study.

OBJECTIVE: To investigate community-acquired pneumonia (CAP) as a cause of severe sepsis in the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial and to evaluate the effect of drotrecogin alfa (activated) (DrotAA) in this subgroup. DESIGN: Retrospective analysis of the severe CAP subgroup in the PROWESS trial. SETTING: Tertiary care institutions in 11 countries. INTERVENTIONS: DrotAA (n = 850), 24 microg.kg.hr for 96 hrs, or placebo (n = 840). PARTICIPANTS: The 1,690 patients with severe sepsis enrolled in the PROWESS trial. MEASUREMENTS AND MAIN RESULTS: Patients were classified as having CAP if lung was the primary site of infection and if they were enrolled directly from home (private residence) with /=25, Pneumonia Severity Index score of >/=4, or CURB-65 (confusion, urea, respiratory rate, blood pressure, age) score of >/=3. CONCLUSIONS: CAP associated with a high Pneumonia Severity Index score, bacteremia, or an intense coagulation and inflammatory response requiring intensive care unit care were indicators of a high risk of death from severe sepsis. In patients with severe sepsis resulting from CAP, a readily identifiable disease, DrotAA, improved survival compared with placebo