Effect of Corticosteroids on Mortality and Clinical Cure in Community-Acquired Pneumonia: A Systematic Review, Meta-analysis, and Meta-regression of Randomized Control Trials

Abstract

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. Corticosteroids may be a beneficial adjunct in the treatment of bacterial pneumonia.

Research question: Is there any benefit of corticosteroid therapy in the management of bacterial CAP among patients requiring hospitalization?

Study design and methods: PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials assessing the use of systemic corticosteroids compared with standard care in the management of CAP. A systematic review, meta-analysis, and Trial Sequential Analysis (TSA) were performed. The primary outcome was all-cause mortality. Secondary outcomes included ICU admission, mechanical ventilation, treatment failure, readmission, and adverse events. Data are presented as risk ratio (RR) with 95% CI, P value, heterogeneity (I²), and TSA-adjusted CIs.

Results: Sixteen trials met the eligibility criteria. All-cause mortality (16 studies [3,842 patients]; RR, 0.85 [95% CI, 0.67-1.07]; P = .17; I² = 14%; TSA-adjusted CI, 0.61-1.09), ICU admission (six studies [2,619 patients]; RR, 0.66 [95% CI, 0.45-0.97]; P = .04; I² = 0%; TSA-adjusted CI, 0.37-1.12), treatment failure (six studies [2,093 patients]; RR, 0.78 [95% CI, 0.37-1.67]; P = .52; I² = 68%; TSA-adjusted CI, 0.02-25.5), and the incidence of adverse events (six studies [2,487 patients]; RR, 1.10 [95% CI, 0.97-1.25]; P = .14; I² = 53%; TSA-adjusted CI, 0.82-2.41) were similar between patients receiving corticosteroids and patients assigned to the control group. The need for mechanical ventilation (eight studies [1,457 patients]; RR, 0.51 [95% CI, 0.33-0.77]; P = .001; I² = 0%; TSA-adjusted CI, 0.20-0.85) was lower among patients receiving corticosteroids compared with those receiving standard care. However, corticosteroid use may be associated with higher rates of hospital readmission (five studies [2,853 patients]; RR, 1.20 [95% CI, 1.05-1.38]; P = .008; I² = 0%; TSA-adjusted CI, 0.89-1.98).

Interpretation: Corticosteroid therapy is associated with a lower incidence of progression to requiring mechanical ventilation among patients hospitalized with CAP. No association was found between corticosteroid therapy and mortality, treatment failure, or adverse events.

Trial registry: PROSPERO; No.: CRD42021279359; URL: https://www.crd.york.ac.uk/prospero/.

Keywords: bacterial pneumonia; community-acquired pneumonia; corticosteroids; meta-analysis; steroids.

Graphical abstract

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-analyses flow chart showing included and excluded trials.

Figure 2

Forest plot showing effect of adjuvant systematic corticosteroids on all-cause mortality in included trials. The size of squares for risk ratio reflects the weight of the trial in the pooled analysis. Horizontal bars represent 95% CIs.

Figure 3

Line graph showing trial sequential analysis for all-cause mortality in included randomized controlled trials. The uppermost and lowermost curves represent trial sequential monitoring boundary lines for benefit and harm, respectively. Horizontal lines represent traditional boundaries for statistical significance. Triangular lines represent the futility boundary. The cumulative z curve represents the trial data. The cumulative z curve crossed neither the conventional nor the TSA boundary for benefit or harm, but did cross the boundary for futility having exceeded the required information size. TSA = Trial Sequential Analysis.

Figure 4

A, B, Forest plots showing the effect of adjuvant corticosteroid therapy on ICU admission (A) or mechanical ventilation (B). The size of squares for risk ratio reflects the weight of the trial in the pooled analysis. Horizontal bars represent 95% CIs.