Do patients with severe community-acquired bacterial pneumonia benefit from systemic corticosteroids?

WHY HAS CORTICOSTEROID USE IN CAP BEEN CONTROVERSIAL?

The use of systemic corticosteroids in CAP has been a subject of debate for years because the exact mechanism by which corticosteroids reduce mortality remains unclear. It has been postulated that corticosteroids may reduce the inflammatory response in the lungs, thereby promoting earlier resolution of CAP and preventing the development of or progression to acute respiratory distress syndrome, ultimately reducing mortality.^1,2

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In addition, studies exploring the potential harms and benefits of corticosteroid therapy in CAP have produced conflicting results. A meta-analysis by Siemieniuk et al³ published in 2015 showed conflicting evidence regarding the use of systemic corticosteroids in CAP but reported benefits that included reduced hospital length of stay, decreased need for mechanical ventilation, and reduced progression to acute respiratory distress syndrome. Results also suggested a potential mortality benefit, but this failed to reach statistical significance.

Table 1^2,4–14 summarizes conclusions from studies that have investigated the role of systemic corticosteroids in CAP, highlighting the conflicting evidence about their risks and benefits over the years.

WHAT HAVE CLINICAL GUIDELINES SAID ABOUT SYSTEMIC CORTICOSTEROIDS IN CAP?

The 2007 combined American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines on CAP did not address the use of corticosteroids. However, the 2019 ATS/IDSA guidelines¹⁵ for the diagnosis and treatment of adults with CAP recommend against using corticosteroids in adults with severe CAP, noting that data on corticosteroid therapy in this group are limited and the findings of benefits in some meta-analyses have not been replicated in others. Additionally, meta-analyses showing a mortality benefit in severe CAP were based on varying definitions of disease severity, making generalization difficult. The ATS/IDSA panel did acknowledge that these guidelines could change with emerging new evidence.

The ATS/IDSA panel¹⁵ also concluded that the evidence against using corticosteroids in nonsevere CAP was strong, citing the fact that benefits seen in larger randomized controlled trials have not been consistently replicated and some randomized controlled trials failed to show differences in clinically meaningful end points. While no study had reported increased mortality in patients treated with corticosteroids, there were concerns about potential harm. Evidence at the time showed a significant rise in hyperglycemia events and possible increased risk of secondary infections with corticosteroid therapy.^2,4–8 As a result, the ATS/IDSA panel¹⁵ recommended against corticosteroid use for nonsevere CAP.

The 2019 ATS/IDSA guidelines¹⁵ agreed with the Surviving Sepsis Campaign recommendations¹⁶ supporting the use of systemic corticosteroids specifically in cases where severe CAP is accompanied by refractory septic shock.

WHEN SHOULD SYSTEMIC CORTICOSTEROIDS BE CONSIDERED?

The pendulum has swung back in favor of corticosteroid use in severe CAP following publication of the landmark CAPE COD (Community-Acquired Pneumonia: Evaluation of Corticosteroids) trial¹² results in 2023, which showed reduced mortality in patients with severe CAP who received hydrocortisone, and with the 2024 release of a focused update by a panel of experts convened by the Society of Critical Care Medicine¹⁷ that addressed the use of corticosteroids in sepsis, acute respiratory distress syndrome, and CAP. Based on 18 randomized controlled trials comparing steroid treatment with no steroid treatment in CAP, the panel concluded that there was moderate certainty of evidence supporting the role of systemic corticosteroids in reducing mortality in patients with severe CAP, but not in those with less severe CAP, and in reducing the need for mechanical ventilation in all hospitalized patients. However, the evidence for shortening intensive care unit or hospital length of stay in hospitalized patients was of lower certainty.¹⁷ As such, the guideline recommends giving corticosteroids to adult patients hospitalized with severe CAP, but makes no recommendation about those with less severe CAP.

Most recently, a meta-analysis by Smit et al¹⁴ that included 8 randomized controlled trials comparing corticosteroids vs placebo in patients hospitalized with CAP showed a 30-day mortality benefit with steroid use. The authors also validated the use of baseline C-reactive protein (CRP) as a key modifier of steroid treatment effect in CAP, showing that patients with high CRP (> 204 mg/L) benefited from corticosteroids, while those with CRP below this threshold did not.

WHAT ARE IMPORTANT CONSIDERATIONS WHEN STARTING PATIENTS ON CORTICOSTEROIDS?

Systemic corticosteroids have been associated with increased hyperglycemia, although the definition of hyperglycemia has varied across studies. The impact of this on patient outcomes remains unclear. In meta-analyses looking at the potential harms and benefits of corticosteroid therapy, the incidence of hyperglycemia was 6% to 12% greater in patients who received systemic corticosteroids, but no evidence of long-term adverse effects, such as increased risk of diabetes or increased use of antihyperglycemic agents 30 days after presentation, was found.^3,14,17

Although there have been concerns that the use of systemic corticosteroids might lead to an increase in secondary or hospital-acquired infections, this was not demonstrated in CAPE COD¹² or the Smit et al¹⁴ study. However, the certainty that corticosteroids are not associated with these adverse effects is low at this time.

There is no evidence showing increased gastrointestinal bleeding risk with systemic corticosteroids.^12,17

Neuropsychiatric side effects like psychosis, insomnia, mood changes, and delirium are common in the elderly, and the risks of these potential side effects must be weighed carefully against the potential benefits.^12,17

WHAT REGIMEN SHOULD BE USED?

The data for specific regimens are mixed. However, the 2025 study by Smit et al¹⁴ suggested that hydrocortisone-based regimens may be superior to regimens using other corticosteroids. Common dosing regimens mentioned in the Society of Critical Care Medicine focused update¹⁷ include the following:

• Intravenous (IV) hydrocortisone 200 mg once, followed by IV infusion at 10 mg per hour for 7 days

• IV hydrocortisone 200 mg daily for 4 or 8 days (based on clinical improvement), then tapered for a total duration of 8 or 14 days

• IV methylprednisolone 0.5 mg/kg every 12 hours for 7 days, given within 36 hours of hospital admission

• Methylprednisolone 40 mg IV bolus, followed by 40 mg daily for days 1 to 7, 20 mg daily for days 8 to 14, 12 mg daily for days 15 to 17, and 4 mg daily for days 18 to 20. This regimen is given via continuous IV infusion in the intensive care unit and then changed to twice daily IV or oral dosing after discharge from the intensive care unit.

These systemic corticosteroid regimens are listed as options that have been tried in different studies in patients with severe CAP, but not in those with less severe CAP, and are not listed in order of efficacy.

THE BOTTOM LINE

Recent evidence in the literature^12,14 and the Society for Critical Care Medicine¹⁷ statement support the use of systemic corticosteroids in severe CAP. Scoring systems like the Pneumonia Severity Index¹² and CRP levels are helpful in assessing severity. Based on the findings from the meta-analysis by Smit et al¹⁴ and the CAPE COD trial,¹² the authors agree with using the Pneumonia Severity Index and CRP greater than 204 mg/L as decision-making tools to determine CAP severity and assess which patients are candidates for systemic corticosteroids.

At the present time, we do not believe the evidence supports systemic corticosteroid use for nonsevere CAP. Due to the heterogeneity of definitions and methodologies across studies, further large-scale randomized controlled trials are needed to further assess the optimal threshold for predicting which patients will benefit from steroid use, particularly as it relates to CRP levels.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.