Efficacy of Corticosteroids in Community-acquired Pneumonia: A Randomized Double-Blinded Clinical Trial

Department of Pulmonary Diseases, Medical Centre Alkmaar, Wilhelminalaan 15, 1812 JD Alkmaar, The Netherlands.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 05/2010; 181(9):975-82. DOI: 10.1164/rccm.200905-0808OC
Source: PubMed


Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia (CAP), possibly by diminishing local and systemic antiinflammatory host response.
To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP.
Hospitalized patients, clinically and radiologically diagnosed with CAP using standard clinical and radiological criteria, were randomized to receive 40 mg prednisolone for 7 days or placebo, along with antibiotics. Primary outcome was clinical cure at Day 7. Secondary outcomes were clinical cure at Day 30, length of stay, time to clinical stability, defervescence, and C-reactive protein. Disease severity was scored using CURB-65 (a severity index for community-acquired pneumonia evaluating Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, and age 65 or older) and Pneumonia Severity Index.
We enrolled 213 patients. Fifty-four (25.4%) patients had a CURB-65 score greater than 2, and 93 (43.7%) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104 (66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109 (77.1%) in the placebo group (P = 0.38 and P = 0.08). Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo. Subanalysis of patients with severe pneumonia did not show differences in clinical outcome. Late failure (>72 h after admittance) was more common in the prednisolone group (20 patients, 19.2%) than in the placebo group (10 patients, 6.4%; P = 0.04). Adverse events were few and not different between the two groups.
Prednisolone (at 40 mg) once daily for a week does not improve outcome in hospitalized patients with CAP. A benefit in more severely ill patients cannot be excluded. Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP.

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Available from: Tjip van der Werf, Dec 07, 2014
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    • "However, insufficient data on non-severe CAP are available. Recently, two randomized double-blind controlled trials including 200 to 300 patients with all severities of CAP found controversial results: the first study using 40 mg of prednisolone for seven days showed no effect on time to clinical stability, with a higher rate of late failure in the corticosteroid group, defined by recurrence of signs and symptoms of pneumonia after 72 hours of admission after an initially beneficial response to treatment [12]. The second study using 4 days of 5 mg of dexamethasone intravenously showed a significantly shorter duration of hospital stay in patients treated with corticosteroids [6,12]. "
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    ABSTRACT: Background Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. Methods/Design This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. Discussion This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. Trial registration 7 September 2009 on ClinicalTrials.gov: NCT00973154.
    Trials 06/2014; 15(1):257. DOI:10.1186/1745-6215-15-257 · 1.73 Impact Factor
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    • "However, this adjunctive promise of systemic CS was not confirmed in several more recent studies. In a large randomised, double-blinded, placebo-controlled trial, Snijders et al. failed to detect beneficial effects of systemic administration of prednisone (40 mg/daily for 7 days) on outcome in patients with CAP, with the frequency of late failure (>72 hours after hospital admission) being significantly (P < 0.04) more common in CS-treated patients [169]. In agreement with these findings, Polverino et al., in a retrospective study covering an approximately 10.5 year period involving 3257 patients who received a mean systemic CS daily dose of 45 mg for varying periods of time, reported that administration of CS did not influence either clinical stability or mortality [170]. "
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    ABSTRACT: Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality among the infectious diseases. Despite the implementation of national pneumococcal polyvalent vaccine-based immunisation strategies targeted at high-risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the control of CAP include the range of bacterial and viral pathogens causing this condition, the ever-increasing problem of antibiotic resistance worldwide, and increased vulnerability associated with steadily aging populations in developed countries. These and other risk factors, as well as diagnostic strategies, are covered in the first section of this review. Thereafter, the review is focused on the pneumococcus, specifically the major virulence factors of this microbial pathogen and their role in triggering overexuberant inflammatory responses which contribute to the immunopathogenesis of invasive disease. The final section of the review is devoted to a consideration of pharmacological, anti-inflammatory strategies with adjunctive potential in the antimicrobial chemotherapy of CAP. This is focused on macrolides, corticosteroids, and statins with respect to their modes of anti-inflammatory action, current status, and limitations.
    Mediators of Inflammation 12/2013; 2013(12):490346. DOI:10.1155/2013/490346 · 3.24 Impact Factor
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    • "Despite their excellent anti-inflammatory efficacy, the use of GCs as therapeutics is often restrained due to two major drawbacks. First, long-term treatment with GCs is often accompanied by severe side effects, such as diabetes, increased risk of infection, osteoporosis, hypertension, and so forth [25, 26]. Occurrence of GCs resistance also restricts many GC-based therapies. "
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    ABSTRACT: Airway diseases such as pneumonia constitute a major health burden on a global scale; untreated pneumonia may develop to severe pneumonia and consequently lead to to fatal episodes of mortality and morbidity. The balance between inflammatory mediators is key for the outcome of the pulmonary infection; elimination of invading pathogen was marked by the release of cytokines and other inflammatory mediators from alveolar macrophages and glucocorticoid steroids (GCs) acting on the inflammatory component. Treatments of severe pneumonia with GCs have been developing for years with inconclusive results. In many cases GCs have been administered empirically without clinical evidence. Recent studies assess beneficial impact on treatment of severe pneumonia by suggesting specific dosage, period of administration, and tapered dosage.
    Mediators of Inflammation 12/2013; 2013:865635. DOI:10.1155/2013/865635 · 3.24 Impact Factor
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