By Divya Gollapudi, MD
Division of General Internal Medicine,
Harborview Medical Center,
Dr. Gollapudi reports no financial relationships in this field of study.
SOURCE: Blum CA, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015. Jan 18; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S0140-6736(14)62447-8)
Despite antibiotic therapy and hospital-based care, severe community-acquired pneumonia still carries a high risk for morbidity and mortality. This is due to an excessive amount of circulating inflammatory cytokines, which can then lead to pulmonary and hemodynamic dysfunction. Corticosteroids are potent anti-inflammatory drugs and may play a role in blunting the systematic inflammatory process present in community-acquired pneumonia. Previously published studies have demonstrated conflicting results regarding the beneficial effects of steroids in community-acquired pneumonia.
To assess the short-term effects of adjuvant corticosteroid therapy, Blum and colleagues performed a large, double-blind randomized control trial at seven tertiary care hospitals in Switzerland. The investigators enrolled adult patients admitted with community-acquired pneumonia within 24 hours of presentation. Exclusion criteria included active intravenous drug use, history of recent gastrointestinal bleed, acute burn injury, severe immunosuppression, adrenal insufficiency, conditions requiring steroid therapy, active tuberculosis, cystic fibrosis, and pregnancy. The 802 patients enrolled in the study were given empiric antibiotics, based on ERS/ESCMID guidelines, at the discretion of the treating provider. The patients were randomized to receive either prednisone 50mg daily or placebo for 7 days. Allocation was concealed, and all study participants, investigators, and data assessors were blinded to treatment allocation.
The primary endpoint was time (days) to clinical stability (defined as stable vital signs, including temperature, heart rate, respiratory rate, blood pressure, mental status, oral intake, and oxygenation) for greater than 24 hours. Additional outcomes were time to hospital discharge, all-cause mortality, complications related to community-acquired pneumonia, and side effects of corticosteroids.
The two groups were similar in baseline characteristics. The median age was 74 years, and 62% were men. The prevalence of medical comorbidities, including diabetes mellitus, chronic obstructive pulmonary disease, heart failure, and renal insufficiency, were similar between the two groups.
The median time to clinical stability was significantly reduced in the prednisone group (3.0 days) compared to the placebo group (4.4 days). This correlated with a shorter hospital course in the prednisone group (6.0 days vs. 7.0 days). There was no difference in total duration of antibiotics, but patients receiving prednisone had fewer days of intravenous antibiotic therapy. The intent-to-treat (n=802) and per-protocol (n=785) populations had similar results. Outcomes were independent of severity of community-acquired pneumonia at admission; however, the authors noted a trend toward larger treatment effect in patients with sepsis. Additionally, complications associated with community-acquired pneumonia were lower in the prednisone group, with an OR 0.49 (0.023 to 1.02, p=0.056). Patients who received prednisone were more likely to require new insulin treatment for in-hospital hyperglycemia (19% vs. 11%); however, rates of insulin treatment were low and equal at day 30. Prednisone therapy was otherwise well tolerated.
In conclusion, Blum and colleagues demonstrate a beneficial effect of adjunct corticosteroids in the treatment of hospitalized patients with community-acquired pneumonia. This was a large, adequately powered, and well-designed study. The study included older patients with a high prevalence of medical comorbidities, allowing for generalizability to patients frequently managed by hospitalists. The study, however, did not include ambulatory patients, and critically ill and septic patients were underrepresented. The results of this trial are compelling, but further research is needed to investigate the effects of steroids on survival before changing practice.