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Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.

ABSTRACT: Improving the outcome of patients with community-acquired pneumonia (CAP) is an ongoing challenge, even in the setting of significant advances in antimicrobial chemotherapy and critical care. Recognition of the underlying involvement of inflammation-mediated organ dysfunction as a determinant of adverse outcomes in CAP has aroused intense interest in the protective potential of adjunctive anti-inflammatory therapies in CAP, particularly the role of corticosteroids (CS). This is the primary topic of the current review which is focused on an evaluation of the latest meta-analyses encompassing both recent and earlier clinical trials, with particular emphasis on the stringent meta-analysis undertaken by Siemieniuk and colleagues (Ann Intern Med 2015;163:519-528). The review highlights the findings and recommendations of these and related published commentaries/critiques, while providing a brief description of those sub-groups of patients who seemingly stand to benefit most from CS therapy. This is preceded by an overview of the mechanisms of the anti-inflammatory activities of CS, the interactions of these agents with macrolide antibiotics, and the potential benefits and risks of short-term administration of CS, concluding with a succinct appraisal of priority issues for ongoing and future research.

SUBMITTER: Feldman C

PROVIDER: S-EPMC4805802 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.

Feldman Charles C Anderson Ronald R

Journal of thoracic disease 20160301 3

Improving the outcome of patients with community-acquired pneumonia (CAP) is an ongoing challenge, even in the setting of significant advances in antimicrobial chemotherapy and critical care. Recognition of the underlying involvement of inflammation-mediated organ dysfunction as a determinant of adverse outcomes in CAP has aroused intense interest in the protective potential of adjunctive anti-inflammatory therapies in CAP, particularly the role of corticosteroids (CS). This is the primary topic ...[more]

PMID: 27076965

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Project description:ImportanceCommunity-acquired pneumonia remains a leading cause of hospitalization, mortality, and health care costs worldwide. Randomized clinical trials support the use of adjunctive corticosteroids, early progressive mobilization, antibiotic switching rules, and dietary interventions in improving outcomes. However, it is uncertain whether implementing these interventions will translate into effectiveness under routine health care conditions.ObjectiveTo evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia.Design, setting, and participantsA double-blind, stepped-wedge, cluster-randomized clinical trial with 90-day follow-up was conducted between August 1, 2016, and October 29, 2017, in the general internal medicine service at 2 tertiary hospitals in Melbourne, Australia, among a consecutive sample of patients with community-acquired pneumonia. The primary analysis and preparation of results took place between May 14 and November 25, 2018.InterventionsTreating clinical teams were advised to prescribe prednisolone acetate, 50 mg/d, for 7 days (in the absence of any contraindication) and de-escalate from parenteral to oral antibiotics according to standardized criteria. Algorithm-guided early mobilization and malnutrition screening and treatment were also implemented.Main outcomes and measuresHospital length of stay, mortality, readmission, and intervention-associated adverse events (eg, gastrointestinal bleeding and hyperglycemia).ResultsA total of 917 patients were screened, and 816 (351 women and 465 men; mean [SD] age, 76 [13] years) were included in the intention-to-treat analysis, with 401 patients receiving the intervention and 415 patients in the control group. An unadjusted geometric mean ratio of 0.95 (95% CI, 0.78-1.16) was observed for the difference in length of stay (days) between the intervention and control groups. Similarly, no significant differences were observed for the secondary outcomes of mortality and readmission, and the results remained unchanged after further adjustment for sex and age. The study reported higher proportions of gastrointestinal bleeding in the intervention group (9 [2.2%]) compared with the controls (3 [0.7%]), with an unadjusted estimated difference in mean proportions of 0.008 (95% CI, 0.005-0.010).Conclusions and relevanceThis bundled intervention including adjunctive corticosteroids demonstrated no evidence of effectiveness and resulted in a higher incidence of gastrointestinal bleeding. Efficacy of individual interventions demonstrated in clinical trials may not necessarily translate into effectiveness when implemented in combination and may even result in net harm.Trial registrationClinicalTrials.gov identifier: NCT02835040.

Dataset Information

Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.

Publications

Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.

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