Severe community-acquired pneumonia: current concepts and controversies

Intensive Care Medicine | Published: 12 January 2026

Abstract

Community-acquired pneumonia, particularly in its severe forms (sCAP), remains a major public health problem due to its frequency, immediate and delayed complications, and the cost of treatment. Although rare, resistant pathogens could make it increasingly difficult to choose an empirical antibiotic treatment. Rapid molecular microbiological diagnostic techniques could help guide this choice, but their role needs to be better evaluated and their cost may be an obstacle to their widespread use. The duration of treatment tends to be decreasing, but could be guided by clinical progression and possibly biomarkers. As a disorder of dysregulated systemic inflammation, sCAP is potentially eligible for immunomodulatory treatment. Three recent high-powered randomized trials on corticosteroids have yielded conflicting results. There is a need to better define which patients are likely to benefit, perhaps those with a marked inflammatory syndrome, and in any case not those with influenza. Some macrolides also have a potential immunomodulatory effect. Other treatments are currently being investigated. Supportive care, particularly respiratory support, remains essential. It is not specific to sCAP and must be tailored to the severity of the patient's condition.

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

 

Corticosteroids in COVID-19 and non-COVID-19 ARDS: a systematic review and meta-analysis

Intensive Care Medicine Published: 19 April 2021

Purpose

Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS.

Methods

The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality.

Results

We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72–0.95, ARR 8.0%, 95% CI 2.2–12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course.

Conclusion

The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.

Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis

 

Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis

 

by Ping Lin, Yuean Zhao, Xiaoqian Li, Faming Jiang and Zongan Liang

 

Critical Care volume 25, Article number: 122 (2021)

 

Background

The possible benefits associated with corticosteroid treatment in acute respiratory distress syndrome (ARDS) patients are not fully known. We conducted an updated meta-analysis to assess the effect of corticosteroids in the treatment of patients with ARDS.

Methods

We systematically searched MEDLINE, Embase, and the Cochrane Library from inception to January 2021 via Ovid to identify randomized controlled trials evaluating the efficacy of glucocorticoids in the treatment of patients with ARDS. The primary outcome was hospital mortality. Secondary outcomes included the number of ventilator-free days at day 28, oxygenation improvement (PaO2/FIO2 ratios), and adverse events.

Results

Nine studies with 1371 participants were analyzed. The pooled analysis revealed that glucocorticoid use was associated with reduced mortality [relative risk (RR), 0.83; 95% confidence interval (CI) 0.74–0.93; P < 0.01; I2 = 37], and the statistical power was confirmed by trial sequential analysis. Glucocorticoids might also significantly increase the number of ventilator-free days at day 28 (mean deviation 3.66 days, 95% CI 2.64–4.68; P < 0.01) and improve oxygenation (standardized mean difference 4.17; 95% CI 2.32–6.02; P < 0.01). In addition, glucocorticoid use was not associated with increased risks of new infection (RR 0.84; 95% CI 0.70–1.01; P = 0.07) and hyperglycemia (RR 1.11; 95% CI 0.99–1.23; P = 0.06).

Conclusions

The use of glucocorticoids might result in reduced mortality in patients with ARDS. Glucocorticoids might be recommended as an adjunct to standard care for ARDS; however, the optimal dose and duration of steroid therapy remains unknown and further studies are needed.

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study

 

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study

 

by Pablo Monedero, Alfredo Gea, Pedro Castro, Angel M. Candela-Toha, María L. Hernández-Sanz, Egoitz Arruti, Jesús Villar and Carlos Ferrando 

 

Critical Care volume 25, Article number: 2 (2021)

 

Background

Critically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.

Methods

This is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.

Results

A total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.

Conclusion

Early use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.

Corticosteroids in severe COVID-19: a critical view of the evidence

 

Corticosteroids in severe COVID-19: a critical view of the evidence

 

by Daniel De Backer, Elie Azoulay and Jean-Louis Vincent 

 

Critical Care volume 24, Article number: 627 (2020)

 

Since December 2019, SARS-CoV-2 has infected millions of people worldwide, causing excess deaths and a surge in demand for ICU beds. With no effective therapies against SARS-CoV-2, randomized trials of several potential therapeutic agents, including steroids, have been conducted. Although use of steroids in patients with ARDS [1] and severe viral pneumonia [2, 3] has been challenged, several arguments support the biological plausibility of steroid use in patients with severe COVID-19. First, autopsy studies in COVID-19 patients showed lymphocyte alveolitis, acute fibrinous injury and organizing pneumonia [4], which are all probably steroid-sensitive. Second, COVID-19 leads to activation of endothelial cells causing not only systemic inflammation but also microvascular thrombosis, pulmonary infarcts and venous thromboembolism [4, 5]. Admittedly, there are also arguments against steroid use. First, viral particles are often found at autopsy [4], and steroids may decrease viral clearance. Second, steroids only influence the inflammatory component of the inflammation–thrombosis–hypoxia interaction [6], suggesting that steroids may be less effective once thrombi have developed.

The RECOVERY trial compared administration of 6 mg/day dexamethasone for 10 days to usual care in 6425 hospitalized patients with SARS-CoV-2 infection. Survival was significantly higher in the dexamethasone-treated patients, especially in the subgroup of 1007 patients receiving invasive mechanical ventilation [7]. As a result of the RECOVERY findings, three further steroid trials, focusing on ICU patients, were stopped prematurely after inclusion of 384 [8], 299 [9] and 149 [10] patients, respectively. A meta-analysis of the available data concluded that administration of systemic steroids was associated with a decrease in 28-day mortality [11]. Nevertheless, although administration of steroids appears promising, several limitations must be considered when interpreting the results

Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome

Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome

Festic, E et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 798–805

Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. 
Design: Double-blind, randomized clinical trial (ClinicalTrials.gov : NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. 
Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). 
Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis

Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis

McKown, A C et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 774–780

Objectives: To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis. Design: Retrospective observational study. Setting: Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center. Patients: A total of 1,080 critically ill patients with sepsis. Interventions: None. 
Measurements and Main Results: The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33–0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5–30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32–0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87–2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63–1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71–1.57; p = 0.783). Conclusions: Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.

pp. 500-506
Effect of corticosteroids on arginine vasopressin–containing vasopressor therapy for septic shock: a case control study.
Bauer, S. R.; Lam, S. W.; Cha, S. S.; Oyen, L. J.
http://zetoc.mimas.ac.uk/wzgw?db=etoc&terms=RN241197900&field=zid

New recommendations for the use of corticosteroids in sepsis : Not so fast !

Salluh , J . I . F . ; Soares , M .
Ovid ( Journals @ Ovid ) via Athens Full Text (01/1995 - /)
Page: 2489 Vol/Issue: 2008 ; VOL 36 ; PART 8
ISSN Print: 0090-3493 E-ISSN: 1530-0293 Print Holdings: Yes
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