PL Detail-Document #310339

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additional insight related to the Recommendations published in

PHARMACISTS LETTER / PRESCRIBERS LETTER

March 2015

Corticosteroids for Community-Acquired Pneumonia

Introduction
Community-acquired pneumonia (CAP) is the
most common cause of death from infectious
disease in developed countries.1 The role of
inflammation in patients with CAP has been
elucidated over the past several decades.2
Pulmonary cytokines protect the body from
infection, but they can also cause systemic
inflammation which can be harmful.3
This
inflammation doesnt appear to be limited to the
acute phase of illness, but rather, persists for a
longer period of time.2 Because of their antiinflammatory effects, corticosteroids have been
studied as adjunctive therapy to antimicrobials in
hospitalized patients with CAP. Study results
have not been consistent, but new and more robust
data are helping clarify their role. This document
reviews the evidence for using corticosteroids in
patients hospitalized with CAP.

Evidence for Steroid Use in CAP Patients

Most data for corticosteroid use in hospitalized
patients with CAP are fairly recent, published
within the past decade. A review published in
2008 included two randomized controlled trials
(RCTs), one open-label RCT, and one
retrospective cohort study. Administration of
steroids (i.e., hydrocortisone, methylprednisolone,
prednisolone) to patients with severe CAP
reduced morbidity and mortality in two out of four
of the studies. The authors of the review
concluded that the use of steroids in patients with
severe CAP should be considered a weak
recommendation, in accordance with evidence
ratings from the Infectious Diseases Society of
America (IDSA)/American Thoracic Society
(ATS) guidelines.1,4 None of the studies showed
worse outcomes in patients who received steroids.
Because of this, the authors also concluded that
steroids are safe for patients with CAP who
require them for other reasons (e.g., asthma,
COPD).1

A randomized, double-blind, placebocontrolled trial (n=213) looking at the use of

steroids in hospitalized patients with CAP was
published in 2010. This study included both nonICU and ICU patients, with 14.4% of patients in
the treatment group and 6.4% of patients in the
placebo group in the ICU. The treatment group
received prednisolone 40 mg orally once daily for
seven days.
Exclusion criteria included
immunosuppression, pregnancy, and pre-existing
conditions requiring the use of steroids. Almost
one-half of patients enrolled had a Pneumonia
Severity Index (PSI) of either class IV or class V
(moderate to high risk). The primary endpoint
was clinical cure (i.e., improvement or resolution
of symptoms without the need for additional
treatment) at day seven. Secondary endpoints
included clinical cure at day 30, length of hospital
stay, and early and late treatment failure.5
There was no significant difference between
groups for clinical cure at day seven. There were
also no significant differences between groups for
secondary outcomes, with the exception of late
failure. Late failure actually occurred more
frequently in patients who received corticosteroids
(19.2% vs 9.2%, p=0.04).5
A larger study was published in 2011
(n=304).3 It was a randomized, double-blind,
placebo-controlled trial looking at the use of
dexamethasone 5 mg given intravenously once
daily for four days to non-ICU inpatients with
CAP.
Exclusion
criteria
included
immunosuppression, pregnancy, or pre-existing
conditions that required treatment with steroids.
Around one-half of patients had a PSI class IV or
V. The primary endpoint was length of hospital
stay.3
The results showed that patients in the
dexamethasone group had a shorter median
hospital stay than those who received placebo (6.5
days vs 7.5 days, 95% confidence interval [CI] 0
to 2 days, p=0.048). There was no difference in
the secondary endpoint of in-hospital mortality or
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(PL Detail-Document #310339: Page 2 of 3)

in severe adverse events between the

dexamethasone and placebo groups. However,
more patients in the dexamethasone group had
hyperglycemia than in the placebo group (44% vs
23%, p<0.0001). There was not a significant
difference between the dexamethasone group and
placebo group in the number of patients who
required additional glucose-lowering therapy
during their hospital stays.3
It may also be worth noting that patients who
received dexamethasone had better social
functioning at 30 days after hospital admission
than those who received placebo.3
One of the newest studies, and also the largest
to date, was published in January 2015. It was a
randomized, double-blind, placebo-controlled
trial (n=785) looking at the use of prednisone
50 mg orally once daily for seven days in adult
inpatients with CAP. This study included nonICU and ICU patients, with 4% of patients in the
treatment group and 6% of patients in the placebo
group in the ICU. Patients were excluded for
conditions such as immunosuppression, current
steroid use, pregnancy, or recent GI bleeding.
Around one-half of patients had PSI class IV or V.
The primary endpoint was time to clinical
stability, defined as time until vital signs were
stable for at least 24 hours. Secondary endpoints
included time to hospital discharge, durations of
total and IV antibiotic treatment, and hospital
readmission.7
The results showed that patients who received
prednisone had a shorter median time to clinical
stability than those who received placebo (3 days
vs 4 .4 days, hazard ratio [HR] 1.33, 95% CI 1.15
to 1.5, p<0.0001).6,7 Median time to hospital
discharge was also shorter in the group who
received prednisone compared to those who
received placebo (6 days vs 7 days, HR 1.19, 95%
CI 1.04 to 1.38, p=0.012). In addition, the
duration of treatment with IV antibiotics was
shorter in the prednisone group (4 days vs 5 days,
difference -0.89 days, 95% CI -1.57 to -0.20 days,
p=0.011). Other secondary endpoints were not
statistically different.7
Hyperglycemia
during
hospitalization
requiring treatment with corrective dose insulin
was more common in the group who received
prednisone (19% vs 11%, OR 1.96, 95% CI 1.31
to 2.93, p=0.0010, number needed to harm
[NNH]=13).7 However, an author of the study
pointed out that the difference in the median daily

insulin requirement for those receiving prednisone

compared to those who received placebo was only
about 7 units. In addition, the NNH for
hyperglycemia requiring corrective dose insulin
during hospitalization in patients without diabetes
was about 25.7
This most recent study was conducted in
Switzerland. As such, when evaluating the results
for a North American population, there are some
things to consider. The hospital length of stay in
the study (about seven days), was longer than the
typical length of stay for CAP in the U.S. (about
five days).8 This fact begs the question of
whether or not there would have been a
statistically significant difference in time to
discharge between the prednisone group and the
placebo group with the shorter length of stay. In
addition, experts point out that the antibiotics
prescribed in the study only included atypical
coverage in about two-thirds of study patients.
However, antibiotics prescribed in the study were
chosen according to Swiss guidelines and groups
appeared to be equally matched with regard to
prescribing of antibiotics. Also, even though a
percentage of patients included in the study would
appear to not have required admission based on
PSI, other studies, including those reviewed in
this document, have shown this is reflective of
general practice.7
Another new but smaller randomized,
double-blind, placebo-controlled trial (n=120)
published in February 2015 looked at the use of
methylprednisolone in ICU patients with severe
CAP and high inflammatory response. The
primary endpoint of this study was treatment
failure, which included early failure and/or late
failure.
The treatment group received
methylprednisolone 0.5 mg/kg/dose every
12 hours for five days.9
The treatment group had a significant
reduction in treatment failure compared to the
placebo group (13% vs 31%, OR 0.34, 95% CI
0.14 to 0.87, p=0.02). This study provides
preliminary evidence for a benefit of
corticosteroids in this specific patient population.9

Conclusion
Evidence is mounting to suggest that the
administration of corticosteroids to inpatients with
CAP has benefits such as reducing length of stay
by about one day [Evidence level A; high-quality
RCT].3,7 The body of evidence also suggests that
More. . .

Copyright 2015 by Therapeutic Research Center

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(PL Detail-Document #310339: Page 3 of 3)

this treatment is safe. Side effects seem to be

limited to a slight increase in the risk of
hyperglycemia [Evidence level A; high-quality
RCT].3,7
The results of a very large study looking at the
use of steroids in ICU patients with sepsis are
expected to be published in 2016. In addition,
updated guidelines for the treatment of CAP are
expected from IDSA in late 2015.
These
forthcoming study results and treatment
guidelines are expected to further clarify the role
of steroids in CAP.
We have more resources for communityacquired pneumonia in our PL Toolbox,
Preventing and Treating Community-Acquired
Pneumonia. In addition, you can access a PSI
calculator at http://www.mdcalc.com/psi-portscore-pneumonia-severity-index-adult-cap/.

4.

5.

6.

7.

8.

9.

Users of this PL Detail-Document are cautioned to use

their own professional judgment and consult any other
necessary or appropriate sources prior to making
clinical judgments based on the content of this
document.
Our editors have researched the
information with input from experts, government
agencies, and national organizations. Information and
internet links in this article were current as of the date
of publication.

Project Leader in preparation of this PL DetailDocument:

Stacy A. Hester, R.Ph., BCPS,
Assistant Editor

randomised, double-blind, placebo-controlled trial.

Lancet 2011;377:2023-30.
Mandell LA, Wunderink RG, Anzueto A, et al.
Infectious Diseases Society of America/American
Thoracic Society consensus guidelines on the
management of community-acquired pneumonia in
adults. Clin Infect Dis 2007;44(Suppl 2):S27-72.
Snijders D, Daniels JM, de Graaff CS, et al.
Efficacy of corticosteroids in community-acquired
pneumonia: a randomized double-blinded clinical
trial. Am J Respir Crit Care Med 2010;181:975-82.
Annane D. Corticosteroids and pneumonia: time
to
change
practice.
Lancet
2015;doi:10.1016/S0140-6736(14)62391-6.
Blum CA, Nigro N, Briel M, et al.
Adjunct
prednisone therapy for patients with communityacquired pneumonia: a multicentre, double-blind,
randomized, placebo-controlled trial.
Lancet
2015;doi:10.1016/S0140-6736(14)62447-8.
CDC.
National Hospital Discharge Survey.
http://www.cdc.gov/nchs/data/nhds/2average/2010
ave2_firstlist.pdf. (Accessed February 18, 2015).
Torres A, Sibila O, Ferrer M, et al. Effect of
corticosteroids on treatment failure among
hospitalized patients with severe communityacquired pneumonia and high inflammatory
response. JAMA 2015;313:677-86.

Levels of Evidence
In accordance with the trend towards Evidence-Based
Medicine, we are citing the LEVEL OF EVIDENCE
for the statements we publish.
Level
A

References
1.

2.

3.

Salluh JI, Povoa P, Soares M, et al. The role of

corticosteroids in severe community-acquired
pneumonia:
a systematic review.
Crit Care
2008;12:R76.
Confalonieri M, Meduri GU.
Glucocorticoid
treatment in community-acquired pneumonia.
Lancet 2011;377:1982-4.
Meijvis SC, Hardeman H, Remmelts HH, et al.
Dexamethasone and length of hospital stay in
patients with community-acquired pneumonia: a

C
D

Definition
High-quality randomized controlled trial (RCT)
High-quality meta-analysis (quantitative
systematic review)
Nonrandomized clinical trial
Nonquantitative systematic review
Lower quality RCT
Clinical cohort study
Case-control study
Historical control
Epidemiologic study
Consensus
Expert opinion
Anecdotal evidence
In vitro or animal study

Adapted from Siwek J, et al. How to write an evidence-based

clinical review article. Am Fam Physician 2002;65:251-8.

Cite this document as follows: PL Detail-Document, Corticosteroids for Community-Acquired Pneumonia.

Pharmacists Letter/Prescribers Letter. March 2015.

Evidence and Recommendations You Can Trust

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Copyright 2015 by Therapeutic Research Center

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