Community Acquired Pneumonia and the Role of Adjunctive Corticosteroids

Pneumonia is a leading cause of hospital admissions and health care resource consumption worldwide and in addition to influenza, remains the eighth leading cause of death in the United States.¹ Because community-acquired pneumonia (CAP) is associated with significant morbidity and mortality, efforts to optimize the management of the infection are a top priority for organizations such as the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS).²

Antibiotics are the mainstay treatment for CAP; however, the additive role of corticosteroids is continually being debated. The 2007 IDSA/ATS Guidelines on the management of CAP briefly mention that there may be some benefit to the use of corticosteroid therapy in patients with severe CAP who are not in shock, but they refrain from making a clear recommendation of their use because of a lack of strong evidence.² Corticosteroids are known to cause a variety of potentially severe adverse effects that often prevents clinicians from using them; however, they may reduce the inflammatory response that occurs in CAP. Therefore, many clinicians remain curious about the role of corticosteroids in CAP, compelling the emergence of new evidence.

A recent systematic review and meta-analysis evaluated the benefits and harms of adjunctive corticosteroids in CAP from 6 different trials.³ The review found no difference in the rate of mortality at 30 days in the corticosteroid group compared to placebo (5.0% vs 5.9%, P = .24). Additionally, the time to clinical stability and hospital length of stay was reduced by 1 day in the corticosteroid group (P<.001); however, the corticosteroid group experienced higher rates of hyperglycemia (22% vs. 12%; P<.001) and rehospitalization (5.0% vs. 2.7%; P = .04). Only studies which included severe CAP patients in the meta-analysis found significant benefit with steroid utilization, whereas, studies that evaluated non-severe patients did not.

Furthermore, a different meta-analysis recently assessed the efficacy of adjunctive corticosteroid treatment in only severe CAP.⁴ This article reviewed 10 randomized controlled trials that enrolled patients with severe CAP—defined as CAP requiring supportive measures in an intensive care unit (ICU).⁵ The results showed that patients who received adjunctive corticosteroids had a reduced hospital mortality rate (RR: 0.49; 95% CI: 0.29—0.85) in addition to a decreased hospital length of stay. There was no difference between the steroid and placebo groups on mechanical ventilation duration. These findings suggest that adding corticosteroids to the management of severe CAP may be beneficial for reducing mortality and hospital length of stay.

With the increasing amount of evidence supporting a reduction in length of stay and mortality rates in severe CAP patients without shock, it is likely that a new recommendation regarding the role of adjunct corticosteroids in CAP will be included in the updated version of the IDSA guideline, despite their adverse effects. This recommendation will likely focus only on ICU patients as general floor patients have not seen benefits in the currently available literature. The guideline is projected to be published in the summer of 2018.

Various steroids and doses have been utilized in the trials investigating the management of severe CAP patients without shock. There are no studies evaluating which steroid or dosing strategy is optimal in severe CAP. Therefore, clinicians have to weigh the evidence against the risk and benefit profiles of various steroids and doses to optimize the care of these patients. Larger randomized clinical trials would shed light on optimal dosing strategies in this patient population.

This article was collaboratively written with Paulushi Patel, a fourth-year PharmD candidate at Chicago State University College of Pharmacy.An earlier version of this article was published on PharmacyTimes.com.

References

1. Centers for Disease Control and Prevention. Leading causes of death. www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Published March 17, 2017. Accessed March 23, 2018.
2. Mandell L, Wunderink R, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin infect Dis. 2007; 44(2): S27-S72.
3. Briel M, Spoorenberg S, Snijders D, et al. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data metaanalysis. Clin Infect Dis. 2018; 66(3):346-54.
4. Wei-Fang W, Qiang F, Guo-Jun H, et al. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: a meta-analysis. Am J of Emerg Med. 2018; 36(2):179-84.
5. Morgan AJ, Glossop AJ. Severe community-acquired pneumonia. BJA Education. 2016; 16(5):167-72.