The Role of Adjunctive Corticosteroids in Community Acquired Pneumonia

Optimizing the management of community-acquired pneumonia (CAP) still remains a goal of organizations like the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS).¹ This is primarily due to the fact that CAP is common and has been associated with a significant amount of morbidity and mortality. Pneumonia is a leading cause of hospital admissions and healthcare resource consumption worldwide.² As of 2017, pneumonia in addition to influenza, remains the eighth leading cause of death in the United States.

While antibiotics are the mainstay for treatment, the role of corticosteroids for adjunctive treatment of CAP has long remained controversial. 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 refrain from making a clear recommendation of their use due to a lack of strong evidence.¹ Severe CAP is defined as CAP requiring supportive measures in an intensive care unit (ICU).³ Corticosteroids are well known to be the cause of a variety of potentially severe adverse effects that often prevents clinicians from utilizing them. However, corticosteroids 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.⁴ 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=0.24). Additionally, the time to clinical stability and hospital length of stay was reduced by one day in the corticosteroid group (p<0.001). However, the corticosteroid group did experience higher rates of hyperglycemia (22% vs. 12%; p<0.001) and rehospitalization (5.0% vs. 2.7%; p=0.04). 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.⁵ This article reviewed 10 randomized controlled trials that enrolled patients with severe CAP. The results found that patients who received adjunctive corticosteroids did have 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 finding suggest that adding corticosteroids to the management of severe CAP may be beneficial to reduce mortality and hospital length of stay.

Another randomized controlled trial that is currently ongoing in Australia is evaluating alternative interventions in CAP therapy that have a high level of evidence, yet are poorly utilized in practice.⁶ Among these interventions is routine corticosteroid use. The trial is set to measure length of hospital stay as a primary outcome, in addition to mortality and readmission rates at 30 and 90 days as secondary outcomes. The investigators will also report any serious adverse events. The results of this trial are anticipated and may further drive new guidelines to incorporate adjunctive corticosteroids in the management of CAP.

With the increasing amount of evidence supporting a reduction in length of stay and mortality rates in severe CAP patients without shock, it is very 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. 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 be welcome to 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.

References

• 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.
• 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.
• Morgan AJ, Glossop AJ. Severe community-acquired pneumonia. BJA Education. 2016; 16(5):167-72.
• 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.
• 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.
• Skinner EH, Lloyd M, Janus E, et al. The IMPROVE-GAP trial aiming to improve evidence-based management of community acquired pneumonia: study protocol for a stepped-wedged randomized controlled trial. Trials. 2018; 19(1): 88.