Corticosteroids for community‐acquired bacterial pneumonia

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One in 18 was helped (death prevented in patients with severe CAP) No one was helped (no death prevented in patients with non-severe CAP) One in 28 was helped (invasive mechanical ventilation prevented) One in 56 was helped (ICU admission prevented regardless of severity) An average of 2 days’ reduction in ICU stay and hospital stay, regardless of severity 5.6% lower risk of death in severe CAP—3.6% lower rate of need for invasive mechanical ventilation 1.8% reduction in ICU admission Pneumonia is a major contributor of morbidity and mortality in the United States and globally.1, 2 Theoretical and laboratory evidence indicate that administration of corticosteroids may be beneficial in treatment of pneumonia.3-5 This evidence-based summary is based on data from a recent systematic review and meta-analysis by Pitre et al.,6 which included 18 randomized controlled trials with 4661 adult (≥18 years old) patients hospitalized with suspected or probable community-acquired pneumonia (CAP). The outcomes of interest included mortality, need for invasive mechanical ventilation (endotracheal intubation), need for intensive care unit (ICU) admission, and length of ICU and hospital stay. The authors of the systematic review conducted a dose–response meta-analysis for the studies with alternative doses or types of corticosteroids, included all severities of disease, but planned an a priori subgroup analysis based on more severe versus less severe patients.6 The systematic review defined trials as more severe if 50% or more of the participants had severe pneumonia scores (pneumonia severity scores of IV or V, CURB65 scores of ≥3, CORB scores of ≥2, SMART-COP scores ≥4) or if ≥50% of patients were admitted to the ICU at the time of randomization. They excluded trials that enrolled predominately (≥80%) patients with Pneumocystis jirovecii pneumonia, inflammatory cases of pneumonia such as organizing pneumonia, chronic obstructive pulmonary disease, COVID-19 pneumonia, other viral cases of pneumonia, empyema, postobstructive pneumonia, or ventilator-associated pneumonia.6 Administration of corticosteroids reduced mortality for patient with severe CAP (relative risk [RR] 0.62, 95% confidence interval [CI] 0.45–0.85, absolute risk difference [ARD] 5.6%, number needed to treat [NNT] 18; 17 trials, 4567patients; moderate certainty). For patients with less severe CAP no significant mortality benefit was found (low certainty).6 The need for invasive mechanical ventilation was reduced with corticosteroids (RR 0.56, 95% CI 0.42–0.74, ARD 3.6%, NNT 28; nine trials, 2895 patients; moderate certainty) as did the need for ICU admission (RR 0.65, 95% CI 0.43–0.97, ARD 1.8%, NNT 56; five trials, 2227 patients; moderate certainty), duration of ICU stay (mean duration [MD] 2.1 days fewer, 95% CI 0.5–3.61 days; 11 trials, 926 patients; low certainty), and duration of hospitalization (MD 2.31 days fewer, 95% CI 0.76–3.85 days; 13 trials, 3442 patients; low certainty).6 The subgroup analysis based on CAP severity did not change these findings. Corticosteroids increased the risk of hyperglycemia (RR 1.76, 95% CI 1.6–2.14, ARD 5.8%, NNH 17; 11 trials, 3362 patients; moderate certainty) but probably did not significantly increase the risk of secondary infections (10 trials, 1970 patients; low certainty) or gastrointestinal bleeding (11 trials, 3368 patients; low certainty).6 The dose–response meta-analysis demonstrated a nonlinear dose–response relationship with the optimal dose of approximately 6 mg of dexamethasone per day for 7 days.6 The primary limitations in evaluating the results of this systematic review are that many of the included trials did not report subgroup analyses based on pneumonia severity, and there was low certainty of evidence for several outcomes. Additionally, these results cannot provide conclusive insights into the consistency of steroid effectiveness across different etiologies of CAP; further studies are necessary to address this question. It remains uncertain whether the effects of corticosteroids are consistent across different causes of bacterial pneumonia (e.g., Streptococcus pneumoniae vs. other pathogens). Future studies should investigate these microbiologic subgroups to clarify this potential variation in treatment response. When comparing different corticosteroids' impact on mortality in patients with severe CAP, hydrocortisone appears to have an edge over other corticosteroids (low to moderate certainty). In addition, hydrocortisone did not have the same superiority when other outcomes were analyzed. This finding has limited impact on the findings of this systematic review as hydrocortisone is generally the corticosteroid of choice in ICU for patients with severe CAP and sepsis. This choice is because of hydrocortisone's high relative mineralocorticoid activity. Further research is needed to confirm whether non-hydrocortisone corticosteroids improves mortality in this context. Although the systematic review reports the findings with specific levels of evidence—a methodologic strength of this systematic review—most conclusions are based on low-certainty evidence, underscoring the need for further research to clarify these questions. Only two conclusions, namely, the reduction in mortality in patients with severe CAP and the risk of hyperglycemia as a side effect, were derived from moderate-certainty evidence. Different trials used varying criteria to define “severe” pneumonia, making it challenging to generalize findings. This variability limits the ability to apply results consistently across patient populations. There is no standardized dosing or treatment duration for corticosteroids across trials, which introduces inconsistencies in the reported effects and complicates determining the optimal approach. Most trials have relatively short follow-up periods, limiting information on the long-term effects of corticosteroid use, such as potential complications. To summarize, the existing evidence supports the use of corticosteroids (namely, hydrocortisone) for hospitalized patients with severe CAP. This recommendation is based on the potential benefits in reduction of mortality, the need for mechanical ventilation and ICU admission, and shortening the duration of hospitalization, reduction in health care costs, and low risk for adverse events. Therefore, we have assigned a color recommendation of green (benefits > harms) to this treatment. This recommendation is in line with the recent recommendation by the Society of Critical Care Medicine, which in their 2024 updates issued a “strong” recommendation for use in hospitalized patient with severe “CAP.”7 Other societies employ a more cautious tone. While they highlight that corticosteroids may benefit a subset of patients, specifically those with severe CAP or those in septic shock, they caution against their widespread use due to risks of side effects and mixed evidence on efficacy.8 The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.