Is treatment with corticosteroids beneficial and safe for people with pneumonia?To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. Two reviewers independently corticosteroid therapy for pneumonia study data twinmuscleworkout steroids assessed risk of bias. Quality of evidence was haldol decanoate injection side effects with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality 12 corticosteroid therapy for pneumonia patients; risk ratio [RR], 0. They also decreased time to clinical stability 5 therapg patients; mean difference,
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By Martin Fried, MD. Welcome to Gamechangers, a series that takes a critical look at the latest in medical literature to answer one important question: Featuring thorough evidence-based review as well as expert commentary, our aim is for this series to help you decide if the results of a given study are, in fact, a gamechanger. Community-acquired pneumonia CAP is a common and potentially serious infection that can lead to hospitalization and death. Until recently, the body of research for use of adjunctive steroids in moderate CAP was limited to two small studies with discordant results.
The STEP study was a multicenter, double-blind, randomized, placebo-controlled trial that took place in seven tertiary care hospitals in Switzerland from Dec to May Patients were eligible for enrollment if they met the following criteria: Exclusion criteria included permanent inability to give informed consent as well as reasons to avoid steroids such as recent GI bleed, immunosuppression and pregnancy, or reasons to withhold steroids in the placebo group such as known adrenal insufficiency or ongoing corticosteroid use.
Eligible patients were designated to receive either 50mg oral prednisone or placebo daily for 7 days through centralized randomization lists and prepackaged medications to ensure appropriate randomization and blinding. Baseline blood samples were drawn and patients were started on European guideline-based antibiotic therapy, which included either amoxicillin-clavulanic acid or ceftriaxone monotherapy. Clarithromycin was added for those patients with atypical organisms or requiring ICU care.
A procalcitonin-guided therapy algorithm was encouraged, but clinical decisions and discharge time was at the discretion of the treating team. The primary outcome of the STEP trial was time to clinical stability defined as stable vital signs with baseline mental status and ability to tolerate oral nutrition for 24 hours. Secondary endpoints included time to discharge, pneumonia recurrence, re-admission, ICU admission, all-cause mortality, duration of total and IV antibiotic treatment, validated disease activity scores specific to CAP and complications of CAP acute respiratory distress syndrome ARDS , empyema, respiratory failure, etc.
Investigators also evaluated adverse effects of glucocorticoids including rate of hyperglycemia, hypertension, delirium, nosocomial infections and weight gain. Of the 1, patients who met inclusion criteria, ended up in final intention-to-treat groups: A third of the patients had pneumonia severity index PSI class IV with the rest approximately evenly distributed across the other four classes. The median time to clinical stability was significantly shorter in the prednisone group than in the placebo group: Among the secondary endpoints, time to discharge 6.
Pneumonia-associated complications were less in the prednisone group, but the difference just missed statistical significance with odds ratio OR: These improvements came at the cost of an increased rate of steroid-associated adverse events, mostly driven by a statistically significant in-hospital hyperglycemia requiring new insulin treatment that largely resolved by day The authors specified pre-defined interaction variables age, initial C-reactive protein concentration, history of COPD, PSI class and blood culture positivity to address possible effect modification, which was not found in the statistical analysis.
This suggests that the higher risk patients within the study — those with older age and PSI class IV and V, for example, did not account for the majority of the difference seen. There are a number of issues regarding the reported baseline characteristics of each patient group.
First, active smoking, prior pneumonia and pneumonia vaccine status were not addressed in baseline characteristics. If differential rates of these variables were found between the study and control groups the statistical analysis should have accounted for that difference.
The effect of culture data on the study results was also lacking. The full methods, published separately  , noted that initial laboratory assessment of all patients included Legionella and pneumococcal urine antigens. These data were not presented in the final manuscript. It does not appear that the effect of any particular isolated microorganism on study outcomes was evaluated. This is important because the clinical benefit of steroids in meningitis appears to be more useful in cases caused by Streptococcus pneumoniae than those caused by Neisseria meningitidis.
If so, we might be able to prevent unnecessary adverse effects of glucocorticoids in a subset of CAP patients where there is no proven benefit of steroids. That said, blindness to precise microbiologic diagnosis mimics usual clinical practice. Finally, it should be noted that all patients in this study were hospitalized, limiting our ability to extrapolate these results to ambulatory settings and those discharged from the emergency department.
The results of the STEP trial are important additions to the canon of existing research in this field. Not only did they enroll a large number of patients across all PSI classes, but they also chose a clinically important primary endpoint for patients with moderate-severity pneumonia where the risk of death and serious adverse reactions are lower. The STEP study provided the power to make that claim. Adjunctive corticosteroids are the standard of care for a number of other infections including bacterial meningitis, pneumocystis pneumonia and acute viral hepatitis.
Whether steroids can improve the outcome of patients with community-acquired pneumonia is an old question that has been unresolved for decades. The publication of two new randomized trials in [9, 10] and 3 recent meta-analyses [5, 6,13] has reinvigorated the debate. The currently available data suggest that the addition of steroids to standard therapy seems to shorten the time to clinical stability, but does not improve survival in the overall population.
A mortality benefit may be present in a subgroup of patients with severe pneumonia. As always, one size does not fit all, and a lot still has to be learned about which patient population will benefit most from the addition of steroids.
Do we treat bacterial and viral pneumonia the same? Do we need to target specific organisms, as for the treatment of meningitis? In addition, we need to better understand what differentiates inflammation that is beneficial to fight infection from an inflammatory response that leads to organ dysfunction. Eventually, this could lead to a well-timed and more individualized treatment approach.
The recently published studies have swung the pendulum more towards steroids in patients with pneumonia, but we still have to learn a lot more before we can win the game. By Martin Fried, MD Peer Reviewed Welcome to Gamechangers, a series that takes a critical look at the latest in medical literature to answer one important question: Why does this matter? What were the study results? What were the flaws of the study? What is the bottom line? Is this study a Game Changer?
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