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



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.



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.



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.



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.
Endocrinology, Diabetology and Metabolism, Department of Internal Medicine and Department of Clinical Research, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Milica
M
Popovic
Endocrinology, Diabetology and Metabolism, Department of Internal Medicine and Department of Clinical Research, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.|Medical University Clinic, Departments of Internal and Emergency Medicine and Department of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Claudine A
CA
Blum
Endocrinology, Diabetology and Metabolism, Department of Internal Medicine and Department of Clinical Research, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
Nicole
N
Nigro
Medical University Clinic, Departments of Internal and Emergency Medicine and Department of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Beat
B
Mueller
Medical University Clinic, Departments of Internal and Emergency Medicine and Department of Endocrinology, Diabetology and Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Philipp
P
Schuetz
Endocrinology, Diabetology and Metabolism, Department of Internal Medicine and Department of Clinical Research, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. mirjam.christ@usb.ch.
Mirjam
M
Christ-Crain
D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D017714:Community-Acquired Infections; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood* / Q000188:drug therapy*; D011241:Prednisone / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D011241:Prednisone
Community-acquired pneumonia; Corticosteroids; Diabetes mellitus; Hyperglycaemia; Pneumonia; Prednisone; Time to clinical stability