Skip to main content
Top
Published in: Diabetologia 12/2016

01-12-2016 | Article

Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients

Authors: Milica Popovic, Claudine A. Blum, Nicole Nigro, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain

Published in: Diabetologia | Issue 12/2016

Login to get access

Abstract

Aims/hypothesis

We have recently shown that adjunct prednisone shortens the time taken to reach clinical stability (time to clinical stability, TTCS) in patients with community-acquired pneumonia (CAP). Considering the hyperglycaemic effects of prednisone, there are concerns about the efficacy and safety of this therapy for diabetic patients with CAP. Our objective was to evaluate whether diabetes and/or hyperglycaemia on admission to hospital has an influence on the effect of corticosteroids on outcome in a well-defined cohort of patients with CAP.

Methods

This is a preplanned subanalysis of a prospective randomised, double-blind placebo-controlled multicentre trial. Patients aged 18 years or older with CAP were eligible and were recruited from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomised (1:1 ratio) to receive either 50 mg of prednisone daily for 7 days or placebo. Allocation was concealed with a prespecified computer-generated randomisation list. Patients, treating physicians, investigators and data assessors were masked to treatment allocation. The primary endpoint was TTCS; secondary endpoints were length of stay, mortality, duration of antibiotic treatment, CAP complications and new insulin requirement at day 30. Furthermore, we analysed whether these endpoints were influenced by a glycaemic dysregulation during the study time.

Results

Of 802 patients randomised (n = 402 in the prednisone, n = 400 in the placebo group), 726 patients were treated per protocol and included in this analysis (n = 362 in the prednisone, n = 364 in the placebo group). Nineteen per cent of 726 patients had diabetes mellitus (n = 66 in the prednisone group, n = 72 in the placebo group). Adjunct prednisone shortened TTCS in diabetic and non-diabetic patients (HR 1.65 [95% CI 1.16, 2.35], p = 0.007; 1.30 [95% CI 1.10, 1.53], p = 0.002) with no evidence for effect modification by diabetes in interaction analysis (p = 0.44). No difference was found in other clinically relevant endpoints. Although adjunct prednisone was associated with glycaemic dysregulation, this did not translate into worse clinical outcomes in either group, and there was no difference in secondary endpoints.

Conclusions/interpretation

The benefit of adjunct prednisone in CAP patients is also valid for those with diabetes or hyperglycaemia on admission. Hyperglycaemia in diabetic patients or due to adjunct prednisone did not have a negative effect on outcome.

Trial registration

ClinicalTrials.gov NCT00973154

Funding

This study was supported by a grant from the Swiss National Foundation and by the Nora van Meeuwen Häfliger Stiftung and the Gottfried Julia Bangerter-Rhyner Stiftung.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lepper PM, Ott S, Nüesch E et al (2012) Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 344:e3397CrossRefPubMedPubMedCentral Lepper PM, Ott S, Nüesch E et al (2012) Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 344:e3397CrossRefPubMedPubMedCentral
2.
go back to reference Yende S, van der Poll T, Lee M (2010) The influence of pre-existing diabetes mellitus on the host immune response and outcome of pneumonia: analysis of two multicentre cohort studies. Thorax 65:870–877CrossRefPubMedPubMedCentral Yende S, van der Poll T, Lee M (2010) The influence of pre-existing diabetes mellitus on the host immune response and outcome of pneumonia: analysis of two multicentre cohort studies. Thorax 65:870–877CrossRefPubMedPubMedCentral
3.
go back to reference Falguera M, Pifarre R (2005) Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus. Chest 128:3233–3239CrossRefPubMed Falguera M, Pifarre R (2005) Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus. Chest 128:3233–3239CrossRefPubMed
4.
go back to reference Fine M, Smith M, Carson C (1996) Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 275:134–141CrossRefPubMed Fine M, Smith M, Carson C (1996) Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 275:134–141CrossRefPubMed
5.
go back to reference Kornum J, Thomsen R, Riis A (2007) Type 2 diabetes and pneumonia outcomes: a population-based cohort study. Diabetes Care 30:2251–2257CrossRefPubMed Kornum J, Thomsen R, Riis A (2007) Type 2 diabetes and pneumonia outcomes: a population-based cohort study. Diabetes Care 30:2251–2257CrossRefPubMed
6.
go back to reference Saibal M, Rahman S (2013) Community acquired pneumonia in diabetic and non-diabetic hospitalized patients: presentation, causative pathogens and outcome. Bangladesh Med Res Counc Bull 38:98–103CrossRef Saibal M, Rahman S (2013) Community acquired pneumonia in diabetic and non-diabetic hospitalized patients: presentation, causative pathogens and outcome. Bangladesh Med Res Counc Bull 38:98–103CrossRef
7.
go back to reference Valdez R, Narayan K (1999) Impact of diabetes mellitus on mortality associated with pneumonia and influenza among non-Hispanic black and white US adults. Am J Public Health 89:1715–1721CrossRefPubMedPubMedCentral Valdez R, Narayan K (1999) Impact of diabetes mellitus on mortality associated with pneumonia and influenza among non-Hispanic black and white US adults. Am J Public Health 89:1715–1721CrossRefPubMedPubMedCentral
8.
go back to reference Miyashita N, Matsushima T, Oka M (2006) The JRS guidelines for the management of community-acquired pneumonia in adults:an update and new recommendations. Intern Med 45:419–428CrossRefPubMed Miyashita N, Matsushima T, Oka M (2006) The JRS guidelines for the management of community-acquired pneumonia in adults:an update and new recommendations. Intern Med 45:419–428CrossRefPubMed
9.
go back to reference Lim WS, van der Eerden MM, Laing R et al (2003) Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58:377–382CrossRefPubMedPubMedCentral Lim WS, van der Eerden MM, Laing R et al (2003) Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58:377–382CrossRefPubMedPubMedCentral
10.
go back to reference Hirata Y, Tomioka H, Sekiya R (2013) Association of hyperglycemia on admission and during hospitalization with mortality in diabetic patients admitted for pneumonia. Intern Med 52:2431–2438CrossRefPubMed Hirata Y, Tomioka H, Sekiya R (2013) Association of hyperglycemia on admission and during hospitalization with mortality in diabetic patients admitted for pneumonia. Intern Med 52:2431–2438CrossRefPubMed
11.
go back to reference Bader M, Abouchehade K, Yi Y (2011) Antibiotic administration longer than eight hours after triage and mortality of community-acquired pneumonia in patients with diabetes mellitus. Eur J Clin Microbiol Infect Dis 30:881–886CrossRefPubMed Bader M, Abouchehade K, Yi Y (2011) Antibiotic administration longer than eight hours after triage and mortality of community-acquired pneumonia in patients with diabetes mellitus. Eur J Clin Microbiol Infect Dis 30:881–886CrossRefPubMed
12.
go back to reference Schuetz P, Friedli N, Grolimund E, Kutz A (2014) Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort. Diabetologia 57:275–284CrossRefPubMed Schuetz P, Friedli N, Grolimund E, Kutz A (2014) Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort. Diabetologia 57:275–284CrossRefPubMed
13.
go back to reference Leibovici L, Yehezkelli Y, Porter A (1996) Influence of diabetes mellitus and glycaemic control on the characteristics and outcome of common infections. Diabet Med 13:457–463CrossRefPubMed Leibovici L, Yehezkelli Y, Porter A (1996) Influence of diabetes mellitus and glycaemic control on the characteristics and outcome of common infections. Diabet Med 13:457–463CrossRefPubMed
14.
go back to reference Becker T, Moldoveanu A (2007) Clinical outcomes associated with the use of subcutaneous insulin-by-glucose sliding scales to manage hyperglycemia in hospitalized patients with pneumonia. Diabetes Res Clin Pract 78:392–397CrossRefPubMed Becker T, Moldoveanu A (2007) Clinical outcomes associated with the use of subcutaneous insulin-by-glucose sliding scales to manage hyperglycemia in hospitalized patients with pneumonia. Diabetes Res Clin Pract 78:392–397CrossRefPubMed
15.
go back to reference McAlister F, Majumdar S, Blitz S (2005) The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care 28:810–815CrossRefPubMed McAlister F, Majumdar S, Blitz S (2005) The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care 28:810–815CrossRefPubMed
16.
go back to reference Meijvis SCA, Hardeman H, Remmelts HHF et al (2011) Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet 377:2023–2030CrossRefPubMed Meijvis SCA, Hardeman H, Remmelts HHF et al (2011) Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet 377:2023–2030CrossRefPubMed
17.
go back to reference Blum CA, Nigro N, Briel M et al (2015) Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 385:1511–1518CrossRefPubMed Blum CA, Nigro N, Briel M et al (2015) Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 385:1511–1518CrossRefPubMed
18.
go back to reference Blum C, Nigro N, Winzeler B (2014) Corticosteroid treatment for community-acquired pneumonia-the STEP trial: study protocol for a randomized controlled trial. Trials 15:257CrossRefPubMedPubMedCentral Blum C, Nigro N, Winzeler B (2014) Corticosteroid treatment for community-acquired pneumonia-the STEP trial: study protocol for a randomized controlled trial. Trials 15:257CrossRefPubMedPubMedCentral
19.
go back to reference Niederman MS, Mandell LA, Anzueto A et al (2001) Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 163:1730–1754CrossRefPubMed Niederman MS, Mandell LA, Anzueto A et al (2001) Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 163:1730–1754CrossRefPubMed
20.
go back to reference Mandell LA, Wunderink RG, Anzueto A et al (2007) Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(suppl 2):S27–S72 Mandell LA, Wunderink RG, Anzueto A et al (2007) Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(suppl 2):S27–S72
21.
go back to reference Fine M, Auble T, Yealy D (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250CrossRefPubMed Fine M, Auble T, Yealy D (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250CrossRefPubMed
23.
go back to reference Egi M, Bellomo R, Stachowski E et al (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105:244–252CrossRefPubMed Egi M, Bellomo R, Stachowski E et al (2006) Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 105:244–252CrossRefPubMed
24.
go back to reference Reynolds R, Labad J, Sears A (2012) Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study. Eur J Endocrinol 166:861–868CrossRefPubMedPubMedCentral Reynolds R, Labad J, Sears A (2012) Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study. Eur J Endocrinol 166:861–868CrossRefPubMedPubMedCentral
25.
go back to reference Agustí C (2003) Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment. Chest J 123:488CrossRef Agustí C (2003) Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment. Chest J 123:488CrossRef
26.
go back to reference Torres A, Sibila O, Ferrer M et al (2015) Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA 313:677CrossRefPubMed Torres A, Sibila O, Ferrer M et al (2015) Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA 313:677CrossRefPubMed
27.
go back to reference Siemieniuk RAC, Meade MO, Alonso-Coello P et al (2015) Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med 163:519–528CrossRefPubMed Siemieniuk RAC, Meade MO, Alonso-Coello P et al (2015) Corticosteroid therapy for patients hospitalized with community-acquired pneumonia. Ann Intern Med 163:519–528CrossRefPubMed
28.
go back to reference Wan Y-D, Sun T-W, Liu Z-Q et al (2016) Efficacy and safety of corticosteroids for community-acquired pneumonia: a systematic review and meta-analysis. Chest 149:209–219CrossRefPubMed Wan Y-D, Sun T-W, Liu Z-Q et al (2016) Efficacy and safety of corticosteroids for community-acquired pneumonia: a systematic review and meta-analysis. Chest 149:209–219CrossRefPubMed
29.
go back to reference Busillo JM, Cidlowski JA (2013) The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab 24:109–119CrossRefPubMedPubMedCentral Busillo JM, Cidlowski JA (2013) The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab 24:109–119CrossRefPubMedPubMedCentral
30.
go back to reference Garcia-Vidal C, Calbo E, Pascual V et al (2007) Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J 30:951–96CrossRefPubMed Garcia-Vidal C, Calbo E, Pascual V et al (2007) Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J 30:951–96CrossRefPubMed
Metadata
Title
Benefit of adjunct corticosteroids for community-acquired pneumonia in diabetic patients
Authors
Milica Popovic
Claudine A. Blum
Nicole Nigro
Beat Mueller
Philipp Schuetz
Mirjam Christ-Crain
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 12/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4091-4

Other articles of this Issue 12/2016

Diabetologia 12/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine