Effect of Corticosteroids on Mortality and Clinical Cure in Community-Acquired Pneumonia

Saleem, Naveed; Kulkarni, Adarsh; Snow, Timothy Arthur Chandos; Ambler, Gareth; Singer, Mervyn; Arulkumaran, Nishkantha

doi:10.1016/j.chest.2022.08.2229

Cited by 55 publications

(28 citation statements)

References 39 publications

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“…We selected this schedule in part to enhance the clinical relevance of the model, as patients with pneumonia usually come to medical attention when their infection has progressed enough to cause symptoms. These ndings are consistent with the results of some recent clinical trials of steroids in COVID-19 ARDS [35,36], non-COVID ARDS [33], and meta-analyses of steroid use in community-acquired pneumonia [37], in which steroid administration provided clinical bene t in patients with pneumonia of differing etiologies but was not associated with signi cantly higher rates of secondary infection.…”

Section: Discussionsupporting

confidence: 89%

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans

Taenaka,

Wick,

Sarma

et al. 2024

Preprint

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Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

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Section: Discussionsupporting

confidence: 89%

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans

Taenaka,

Wick,

Sarma

et al. 2024

Preprint

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“…The available evidence seems to indicate that not all patients are eligible to benefit from them, and the data have been controversial. [91][92][93] Nevertheless, there is evidence that corticosteroids may be useful in sCAP patients with a high inflammatory response. Torres et al, in a randomized clinical trial with methylprednisolone demonstrated a reduction in treatment failure in sCAP patients with CRP greater than 150 mg/L at admission.…”

Section: Adjunctive Therapymentioning

confidence: 99%

Treatment Failure and Clinical Stability in Severe Community-Acquired Pneumonia

Méndez,

González-Jiménez,

Mengot

et al. 2024

Semin Respir Crit Care Med

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“…Although previous systematic reviews and meta-analyses have demonstrated similar findings, we believe that this study provides important contributions. Specifically, as compared to the most recent review addressing this topic, 51 of which there are significant methodological limitations and the absence of the CAPE COD trial, 52 we have specifically evaluated for subgroup effect based on the severity of CAP and assess the credibility of potential subgroup effect using the ICEMAN tool. This subgroup analysis demonstrates that the effects of corticosteroids on mortality are limited to those with severe disease.…”

Section: In Relation To Other Findingsmentioning

confidence: 99%

Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis

et al. 2023

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Introduction International guidelines provide heterogenous guidance on use of corticosteroids for community-acquired pneumonia (CAP). Methods We performed a systematic review of randomized controlled trials examining corticosteroids in hospitalized adult patients with suspected or probable CAP. We performed a pairwise and dose-response meta-analysis using the restricted maximum likelihood (REML) heterogeneity estimator. We assessed the certainty of the evidence using GRADE methodology and the credibility of subgroups using the ICEMAN tool. Results We identified 18 eligible studies that included 4661 patients. Corticosteroids probably reduce mortality in more severe CAP (RR 0.62 [95% CI 0.45 to 0.85]; moderate certainty) with possibly no effect in less severe CAP (RR 1.08 [95% CI 0.83 to 1.42]; low certainty). We found a non-linear dose-response relationship between corticosteroids and mortality, suggesting an optimal dose of approximately 6 mg of dexamethasone (or equivalent) for a duration of therapy of 7 days (RR 0.44 [95% 0.30 to 0.66]). Corticosteroids probably reduce the risk of requiring invasive mechanical ventilation (RR 0.56 [95% CI 0.42 to 74] and probably reduce intensive care unit (ICU) admission (RR 0.65 [95% CI 0.43 to 0.97]) (both moderate certainty). Corticosteroids may reduce the duration of hospitalization and ICU stay (both low certainty). Corticosteroids may increase the risk of hyperglycemia (RR 1.76 [95% CI 1.46 to 2.14]) (low certainty). Conclusion Moderate certainty evidence indicates that corticosteroids reduce mortality in patients with more severe CAP, the need for invasive mechanical ventilation, and ICU admission. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-023-08203-6.

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Effect of Corticosteroids on Mortality and Clinical Cure in Community-Acquired Pneumonia

Cited by 55 publications

References 39 publications

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans

Treatment Failure and Clinical Stability in Severe Community-Acquired Pneumonia

Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis

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