Corticosteroids in the Setting of Community-Acquired Pneumonia

Systemic corticosteroids are commonly prescribed to treat acute exacerbations of respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Current guidelines recommend the acute use of steroids in these patient populations as they have been shown to shorten recovery time and improve lung function and arterial hypoxemia.¹ As community-acquired pneumonia (CAP) also involves an inflammatory process, it has been hypothesized that the use of corticosteroids may also be beneficial in these patients. Antibiotics are the first-line treatment of CAP, however patients remain at a high risk for long-term morbidity and mortality. 

Recently 2 large trials have concluded that the use of corticosteroids in patients with CAP may improve patient outcomes and reduce treatment failure. Should all patients with CAP receive adjunctive corticosteroids in addition to antibiotic therapy? 

A Case Study

WG is a 67-year-old man with a past medical history of hypertension and dyslipidemia who presents to your outpatient clinic. He is complaining of new-onset cough with yellow sputum production, shortness of breath, and fever. His vital signs include a respiratory rate of 22 breaths/min, a heart rate of 95 beats/min, blood pressure of 120/78 mm Hg, and a temperature of 38.1°C. The C-reactive protein (CRP) level is measured at 67 mg/L.

After examining WG, you diagnose him with CAP and prescribe a 5-day course of azithromycin. In addition to antibiotics, should a short course of corticosteroids also be prescribed?

The Evidence

The concept of using corticosteroids for adjunctive treatment of pneumonia has been around since the early 1950s.² Retrospective and prospective studies evaluating this practice have revealed mixed results. Several meta-analysis concluded that corticosteroids might be beneficial, but a large randomized, controlled trial would be needed to appropriately assess this practice.³

Two large, randomized, controlled clinical trials have recently evaluated the use of adjunctive corticosteroids in patients with CAP. The first of these studies assessed the efficacy of prednisone 50 mg orally once daily for 7 days versus placebo in patients admitted to the hospital with a diagnosis with CAP—which is defined as infiltrate on chest radiographic and at least 1 clinical sign or symptom. All patients received background therapy with guideline-based antibiotics.³

The results of this first showed that the use of corticosteroids significantly reduced the time to clinical stability—defined as time until stable vital signs for 24 hours or longer—to 3 days versus 4.4 days (hazard ratio [HR], 1.33 P < .0001) and the time to hospital discharge to 6 days versus 7 days (HR, P = .012). Prednisone had no effect on recurrent readmission, hospital readmission, or mortality.³

The second of these trials evaluated the corticosteroids in patients with severe CAP—defined by modified American Thoracic Society criteria or risk class V for the Pneumonia Severity Index (PSI)—and a CRP level of greater than 150 mg/L at admission. Patients were randomized to receive intravenous methylprednisolone 0.5 mg/kg every 12 hours or placebo, in addition to guideline-based antibiotic therapy. Treatment with adjunctive corticosteroids was associated with a significant reduction in treatment failure, including a broad range of clinical outcome measures. Treatment with corticosteroids demonstrated no effect on mortality.⁴

While these studies support adjunctive corticosteroids in patients with CAP, the context of these studies must be highlighted. Both of these studies included patients with a pneumonia severity index of IV or V, thus indicating the need for inpatient treatment due to more severe disease and/or more severe underlying comorbidities at baseline. One of the studies also included patients with an elevated CRP, indicating a high baseline inflammatory burden and selecting out the patients who stand the most to gain from corticosteroids. Furthermore, the antibiotic regimens that were utilized in addition to the corticosteroids would likely be different than the regimens used for those patients treated in an outpatient setting. Therefore, it is unclear if the beneficial effects of the corticosteroids would be maintained in a less severely ill population or with simpler oral antibiotic regimens. 

Outcome of the Case

Based on WG’s CURB-65 and PSI scores, he does not warrant inpatient treatment and can be treated as an outpatient with oral antibiotics. While the use of adjunctive corticosteroids is an enticing option, available evidence only supports this practice in patients requiring hospitalization. The patients who benefited from corticosteroids in 1 study⁴ had a baseline CRP > 150 mg/L; WG has a CRP of 67 mg/L, which likely indicates that he would not be a candidate for the adjunctive treatment. Therefore, the patient should be treated with azithromycin alone until future studies establish the efficacy of adjunctive corticosteroids in the outpatient management of CAP. n

Eric A. Dietrich, PharmD, BCPS, graduated from the University of Florida College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the University of Florida Colleges of Pharmacy and Medicine in Gainesville, FL. 

Kyle Davis, PharmD, BCPS, graduated from the University of Florida College of Pharmacy in 2011 and completed a PGY-1 at Jackson Memorial Hospital and a PGY-2 in internal medicine at Indiana University Health and Butler College of Pharmacy. He currently works at Jackson Memorial Hospital in Miami, FL. 

References:

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of COPD. 2015. www.goldcopd.org/guidelines -global-strategy-for-diagnosis-management.html. Accessed November 2015.
2. Wagner HN, Bennett IL, Lasagna L, et al. The effect of hydrocortisone upon the course of pneumococcal pneumonia treated with penicillin. Bull Johns Hopkins Hosp. 1956;98(3):197-215.
3. Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511-1518.
4. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677-686.