Any Benefit to Adjunct Prednisone Therapy in Community Acquired Pneumonia?

PneumoniaBackground: Respiratory tract infections and pneumonia are the 3rd leading cause of death worldwide.  Although morbidity and mortality has improved slightly with the advent of antibiotics, there is still a significant long-term morbidity and mortality associated with this disorder.  It is well known that in pneumonia, there is an excess release of circulating inflammatory cytokines which cause further pulmonary dysfunction. Maybe the use of systemic corticosteroids, which have anti-inflammatory effects, could help attenuate this systemic inflammatory process and thus improve outcomes. So is there any benefit to adjunct prednisone therapy in community acquired pneumonia?

Are there studies evaluating the use of steroids in pneumonia?

StudyYear of StudyType of CorticosteroidMorbidity/Mortality Benefit or Harm with Steroids in Pneumonia
[5]1956HydrocortisoneMortality Benefit
[4]2005HydrocortisoneMortality Benefit
[3]2007"Systemic Steroids"Mortality Benefit
[2]2010PrednisoloneNo Benefit in Mortality but increase pneumonia recurrence rate with steroids
[1]2011DexamethasoneDecrease Length of Hospital Stay by 1 Day

Systematic Review and Meta-Analysis

Are there larger studies or reviews evaluating the use of steroids in pneumonia?

Systematic Reviews:

  • Siempos II et al (2008) [1]
  • Chen Y et al (2011) [2]

Meta-Analyses:

  • Nie W et al (2012) [3]
  • Shafiq M et al (2013) [4]
  • Lamontagne F et al (2013) [5]

Conclusion of all larger trials: Adjunct corticosteroids in community acquired pneumonia might be beneficial, but a large, adequately powered randomized trial is warranted

Hot off the press

What is the most recent literature evaluating adjunct corticosteroids in community acquired pneumonia?

Blum CA et al (January 2015) [6]

Methods:

  • Largest, Double-Blind, Multicenter, Randomized, Placebo Controlled Trial
  • 785 Patients from 7 Hospitals in Switzerland
  • Augmentin or Rocephin Alone for Community Acquired Pneumonia + Clarithromycin if Concern for ICU/Legionella
  • Prednisone 50mg PO qDay vs Placebo PO qDay x7days

Outcomes:

  • Primary Outcome – Time to clinical stability (Days until stable vital signs x24hours)
  • Secondary Outcome – Hospital Length of Stay, IV Antibiotics

Results:

  • Median Time to Clinical Stability: 3 days (prednisone) vs 4.4 days (placebo)
  • Hospital Length of Stay: 6 days (prednisone) vs 7 days (placebo)
  • Need for IV Antibiotics: 4 days (prednisone) vs 5 days (placebo)
  • Incidence of Hyperglycemia Requiring Insulin Tx: 19% (prednisone) vs 11% (placebo)

Limitations:

  • Only admitted patients, therefore we don’t know how this works in patients treated as outpatients
  • The study was not powered for mortality
  • The primary endpoint is a combined endpoint of several vital signs
  • Asthma patients not teased out in this study
  • Prednisone has a bitter taste and therefore may have unblinded patients
  • Hyperglycemic events may have unblinded researchers

Conclusion of Study: Prednisone treatment for 7 days in patients with community-acquired pneumonia shortens time to clinical stability without an increase in complications

Take Home Message

Although this study certainly showed some benefit in patient centered outcomes and hospital costs/efficiency, there was an increase in hyperglycemia and the study was not powered to show mortality benefit.  We are still lacking a large, adequately powered randomized trial and therefore the use of systemic steroids should not be adopted into clinical practice at this time

Other Blog Posts on the Topic:

Ryan Radecki at Emergency Medicine Literature of Note

References

  1. I.I. Siempos, K.Z. Vardakas, P. Kopterides, and M.E. Falagas, "Adjunctive therapies for community-acquired pneumonia: a systematic review.", The Journal of antimicrobial chemotherapy, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18641037
  2. Y. Chen, K. Li, H. Pu, and T. Wu, "Corticosteroids for pneumonia.", The Cochrane database of systematic reviews, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21412908
  3. W. Nie, Y. Zhang, J. Cheng, and Q. Xiu, "Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis.", PloS one, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23112872
  4. M. Shafiq, M.S. Mansoor, A.A. Khan, M.R. Sohail, and M.H. Murad, "Adjuvant steroid therapy in community-acquired pneumonia: a systematic review and meta-analysis.", Journal of hospital medicine : an official publication of the Society of Hospital Medicine, 2012. http://www.ncbi.nlm.nih.gov/pubmed/23184813
  5. F. Lamontagne, H. Quiroz Martinez, N.K.J. Adhikari, D.J. Cook, K.K.Y. Koo, F. Lauzier, A.F. Turgeon, M.E. Kho, K.E.A. Burns, C. Chant, R. Fowler, I. Douglas, Y. Poulin, K. Choong, N.D. Ferguson, and M.O. Meade, "Corticosteroid use in the intensive care unit: a survey of intensivists.", Canadian journal of anaesthesia = Journal canadien d'anesthésie, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23606231
  6. C.A. Blum, N. Nigro, M. Briel, P. Schuetz, E. Ullmer, I. Suter-Widmer, B. Winzeler, R. Bingisser, H. Elsaesser, D. Drozdov, B. Arici, S.A. Urwyler, J. Refardt, P. Tarr, S. Wirz, R. Thomann, C. Baumgartner, H. Duplain, D. Burki, W. Zimmerli, N. Rodondi, B. Mueller, and M. Christ-Crain, "Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial.", Lancet, 2015. http://www.ncbi.nlm.nih.gov/pubmed/25608756

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Salim Rezaie