C-reactive protein to guide steroid use in severe community-acquired pneumonia
Exploring nuance in the latest interim CAP guideline update
A 2025 interim guideline document published by a major critical care society recommends that patients with severe community-acquired pneumonia not due to influenza should receive systemic corticosteroids, such as hydrocortisone 200 mg daily.
The guidance echoes that of another major critical care society in 2024, which also recommended steroids for severe CAP.
But guidelines are never one-size-fits-all, and every patient deserves a thoughtful and individualized treatment plan.
Are there patients with severe CAP who are more likely to benefit from steroids, and how can they be identified?
C-Reactive Protein May Predict Steroid Responsiveness
In the CAPE COD trial, which strongly influenced the authors of one of the guideline documents, steroids were found to have a differential benefit based on C-reactive protein level.
Patients with CRP >15 mg/dL who received hydrocortisone had an absolute 7% lower risk of death (5% vs. 12%) compared to those receiving placebo.
This effect was explored further by Smit et al (Lancet Respiratory Medicine 2025), in a meta-analysis of 8 randomized trials (n=3,224) for which patient-level data (not just aggregated data) were available.
In that meta-analysis, corticosteroids reduced mortality overall (6.6% vs. 8.7%, odds ratio 0.72, 95% CI 0.56-0.94), including patients with severe and nonsevere CAP.
In the two most recent trials (CAPE COD and ESCAPE, combined n=1,355), elevated CRP predicted a mortality benefit with corticosteroids:
Among patients with a CRP level > 20.4 mg/dL (n=630), those receiving corticosteroids had 6% mortality, compared to 13% of those receiving placebo.
Among those with CRP ≤ 20.4 mg/dL (n=725), steroids had no apparent benefit (odds ratio 0.98, 95% CI 0.63-1.50).
Corticosteroids significantly increased the rate of hyperglycemia (odds ratio, 2.5) and the hospital readmission rate (7% vs. 3.7% with placebo).
Guidelines’ Mention of CRP’s Role
The thoracic society’s panel suggested that in individual patients, elevated CRP should strengthen their recommendation for steroids, and a normal or low CRP should weaken it.
Specific CRP thresholds were not mentioned, but levels >15 or >20 mg/dL would best approximate the relationships observed in the CAPE COD and ESCAPE trials, in which significant heterogeneity of treatment effect was observed with corticosteroids. This does not imply that patients with CRP lower than 15 mg/dL should not receive steroids.
Other factors that strengthened the recommendation were ICU admission, respiratory failure, and rapid onset and progression of symptoms of pneumonia.
CRP Shouldn’t Determine High-Stakes Antibiotic Decisions
Falling C-reactive protein levels have been studied as an adjunctive decision aid in discontinuing antibiotics, helping to reduce antibiotic exposure without an obvious harm signal in some studies.
However, CRP has been less well-studied than procalcitonin and appears possibly inferior to procalcitonin for this purpose. CRP should not be the sole or even the primary determining criterion for high-stakes antibiotic decisions (starting, stopping, or modifying agents).
Conclusions
Critical care professional society guidelines advise the provision of systemic corticosteroids for patients with severe community-acquired pneumonia. No specific agent or doses are advised, but hydrocortisone 200 mg daily was used in the most influential randomized trial (CAPE COD).
C-reactive protein appears to predict responsiveness to steroids in patients with community-acquired pneumonia. A CRP threshold of >15 mg/dL or >20 mg/dL may more strongly predict a benefit, as these patients were more likely to survive in two randomized trials. Benefits short of mortality reduction (e.g., faster improvement) might occur at lower elevations of CRP than these thresholds. One professional society considers an elevated CRP as a factor strengthening the indication for steroids, and a normal CRP as weakening the recommendation.
CRP should not be used as a primary criterion in making high-stakes antibiotic decisions.
Excellent post -- why this bloodwork (and BNP) seem to be ignored is strange. It's another tool in your decision making data set. Nothing will beat history/physical/imaging but if someone's on the vent, CRP 20 (not influenza or aspiration since CAPE COD avoided that) -- why not give steroids at this relatively modest dose, understanding that harm is not great. A COPDer sneezes and gets 60q6 of methylpred....no questions, less RCT data. Perhaps it should be drawn in that situation too...:) *Hope the play is going well. Am in Northeast so bit tough in order to get to ATL to see but would have loved too.