Level 2 [mid-level] evidence
Community-acquired pneumonia is a major public health concern leading to millions of primary care and hospital visits each year. The Infectious Diseases Society of America and American Thoracic Society (IDSA/ATS) 2007 guidelines recommend empiric antibiotic for treatment of community-acquired pneumonia. Adjunctive corticosteroids are not currently recommended, but a growing body of evidence suggests they may provide clinical benefit.
Two randomized trials published in 2015 compared adjunctive corticosteroids vs. placebo in adults hospitalized with community-acquired pneumonia (JAMA. 2015;313:677; Lancet. 2015;385:1511).
The first trial from Torres et al. published in February 2015 (JAMA. 2015;313:677) examined the effect of corticosteroid treatment on treatment failure and in-hospital mortality in adults with severe community-acquired pneumonia.
Treatment failure was evaluated as a composite outcome, with early treatment failure defined as shock, new need for invasive mechanical ventilation, or death within three days; and late treatment failure defined as radiographic progression, persistent severe respiratory failure, shock, new need for invasive mechanical ventilation, or death between three and five days.
In this trial, 120 adults (mean age, 65 years) with severe community-acquired pneumonia were randomized to methylprednisolone (0.5 mg/kg per 12 hours IV bolus) vs. placebo for five days in addition to antibiotic treatment. All patients had a high inflammatory response at admission, defined as C-reactive protein levels greater than 150 mg/L. Septic shock was present in 17% of patients randomized to methylprednisolone and in 31% of patients randomized to placebo (no P value reported).
Although there was no difference between groups in early treatment failure (10% per group), methylprednisolone was associated with a significantly decreased risk of late treatment failure compared with placebo (3% vs. 25%, P = 0.001, NNT 5). There were also no significant differences in in-hospital mortality, length of hospital or ICU stay, time to clinical stability, or adverse events.
The second trial by Blum et al. recently published in The Lancet (2015;385:1511) evaluated oral corticosteroids in a larger population of adults hospitalized with pneumonia of any severity. The primary outcome of this trial was time to clinical stability, a composite outcome defined as time until vital signs were stable for 24 or more hours.
Here, 802 adults (mean age, 74 years) were randomized to prednisone (50 mg daily) vs. placebo for seven days in addition to antibiotic treatment. Patients presented with a number of comorbidities, including renal insufficiency in 32%, antibiotic pretreatment in 23%, diabetes mellitus in 20%, heart failure in 18%, chronic obstructive pulmonary disease in 17%, and coinfection in 12%.
Comparing prednisone with placebo, time to clinical stability was three days vs. 4.4 days (P < 0.0001) and length of hospital stay was six days vs. seven days (P = 0.012). Consistent results were reported in subgroup analyses by age, median C-reactive protein concentration, history of chronic obstructive pulmonary disease, severity of pneumonia, or blood culture positivity. There were no significant differences in recurrent pneumonia, hospital readmission, or pneumonia-associated mortality.
Together, the results of these trials suggest that the addition of corticosteroids to antibiotic treatment may improve the clinical course of disease in patients hospitalized with pneumonia, regardless of disease severity. There are several considerations that may limit the generalizability of these findings, however. Neither trial considered patients with community-acquired pneumonia treated in an outpatient setting. The trial by Torres et al. evaluated corticosteroids in a very specific population of patients with severe pneumonia plus high inflammatory responses.
Also, the decreased rate of late treatment failure observed in the methylprednisolone group in this trial may have been influenced by the lower percentage of patients with septic shock at baseline randomized to this treatment. While the trial by Blum et al. evaluated the use of adjunctive corticosteroids in a broader patient population, the individual components of the time to clinical stability composite outcome were not reported. One component of this outcome is a temperature of 37.8°C (100°F) or lower.
Treatment with corticosteroids can result in a decrease in fever, and a change in body temperature alone cannot be ruled out. Absence of fever is also a common component of discharge criteria, which may confound the effect of corticosteroids on decreasing the length of hospital stay as well.
The results of these trials show potential benefit for adjunctive corticosteroid use in hospitalized patients with community-acquired pneumonia, but further analysis is required to determine at what dose and in which patient populations they are truly effective.
Alan Ehrlich, MD, is a deputy editor for DynaMed, in Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.
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