WHAT’S NEW IN INFECTIOUS DISEASES
Adjuvant steroid therapy in community-acquired
pneumonia
Caroline Bell Sisson, MMS, PA-C
ABSTRACT
Despite medical advances, pneumonia is a leading cause
of death worldwide. Because inflammation is a key
defense mechanism, adjuvant corticosteroid therapy has
long been considered but never widely recommended to
treat pneumonia. New research is exploring potential
benefits of this therapy, including reduced time to clinical
stability, reduced hospital stay, reduced rates of treatment
failure, and prevention of complications.
Keywords: pneumonia, corticosteroids, adjuvant therapy,
prednisone, inflammation, community-acquired
D
espite advances in antibiotic treatment and sup-
portive care, community-acquired pneumonia
remains a source of substantial disease burden.
Twenty-three percent of patients in North America who
require hospitalization for pneumonia die.1 The disease may
be accompanied by serious complications including respira-
tory failure, septic shock, and acute respiratory distress
syndrome (ARDS). Severe ARDS carries a mortality of 52%.2
Corticosteroids provide anti-inflammatory effects, and
inflammatory physiology may play a role in pneumonia.
The host response to a pathogen includes release of inflam-
matory cells and cytokines, propagating a cycle of inflam-
mation. This inflammation promotes endothelial
dysfunction and may result in dissemination of the patho-
gen into extrapulmonary space, initiating a systemic inflam-
matory response.
Adjuvant therapy with corticosteroids has been investi-
gated since at least 1955, when hydrocortisone was stud-
ied in patients with pneumococcal pneumonia.3 Despite
evidence for its utility, corticosteroid therapy has not been
common clinical practice, likely due in part to a formi-
Caroline Bell Sisson is an assistant professor in the PA program
at Wake Forest School of Medicine in Winston-Salem, N.C., and
affiliate professor in the College of Health Sciences at Appalachian
State University in Boone, N.C. The author has disclosed no potential
conflicts of interest, financial or otherwise.
Mark E. Archambault, DHSc, PA-C, department editor
DOI:10.1097/01.JAA.0000520547.38699.83
Copyright © 2017 American Academy of Physician Assistants
52 www.JAAPA.com
Copyright © 2017 American Academy of Physician Assistants
dable adverse reaction profile and a dearth of consistent
clinical trials. Increasing discussion about the use of cor-
ticosteroids in community-acquired pneumonia follows
emerging evidence of improved outcomes. These include
reduced time to clinical stability, reduced rates of treatment
failure, possible reduction in ARDS, reduced need for
mechanical ventilation, and reduced hospital stay.4-7 These
findings have been confined to patients requiring hospital-
ization for bacterial community-acquired pneumonia.
RECENT RESEARCH
In a large randomized controlled trial of patients receiving
a 7-day course of 50 mg of oral prednisone daily versus
placebo, patients in the treatment group reached clinical
stability more quickly than those on placebo (mean differ-
ence, 1.4 days).4 The study involved 785 adults, including
those with chronic comorbidities such as chronic obstruc-
tive pulmonary disease (COPD). Although the population
studied is reflective of many patients requiring inpatient
treatment of community-acquired pneumonia, the caveat
lies in the antibiotics used. The trial was conducted in
Switzerland and followed European Respiratory Society/
European Society of Clinical Microbiology and Infectious
Disease guidelines. Most patients were treated with amox-
icillin and clavulanic acid; patients requiring ICU treatment
and those with suspected Legionella were treated with a
beta lactam and clarithromycin. This variation from Infec-
tious Disease Society of America (IDSA) guidelines is
significant because it excludes the well-established anti-
inflammatory role of macrolides.8
A smaller randomized controlled trial demonstrated
reduced treatment failure in patients who received an IV
bolus of 0.5 mg/kg per 12 hours of methylprednisolone
versus placebo for 5 days.5 The small study population of
112 reflects strict inclusion criteria: a C-reactive protein
of greater than 150 mg/L at admission as well as severe
community-acquired pneumonia as defined by American
Thoracic Society (ATS) or risk class V for the Pneumonia
Severity Index. The conclusions drawn from such a specific
population are not easily generalizable. Also, adrenal func-
tion was not measured in the study, making it difficult to
assess whether this represents a new role for corticoste-
roids in community-acquired pneumonia. Current IDSA
Volume 30 • Number 7 • July 2017

guidelines recommend corticosteroids in patients with
severe community-acquired pneumonia who require vaso-
pressors and have an insufficient adrenal response.8
A possible link between adjuvant corticosteroid therapy
and reduced risk of ARDS has been suggested in two recent
meta-analyses.6,7 These results may be met with cautious
optimism given a small number of overall events and the
lack of prespecification of this outcome in analyzed stud-
ies.6,7 One of these meta-analyses also demonstrates a
reduced need for mechanical ventilation and potentially
lower ICU admission rates.6 The greatest relative reduction
in mechanical ventilation was in larger studies examining
patients with less-severe pneumonia compared with stud-
ies examining patients with severe pneumonia. Reduced
ICU admission was seen in the three trials studied, which
all examined patients with less-severe community-acquired
pneumonia. However, the confidence interval for the risk
reduction crosses 1 (RR 0.69; 95% CI 0.46-1.03) and
therefore cannot be presumed valid. Although these find-
ings suggest increased benefit in patients with less-severe
community-acquired pneumonia, they have been considered
spurious, as the benefit may reflect differences in the trials
studied. Evidence for reduced duration of hospital stay is
more compelling. With three studies examined and a total
of 1,288 patients, a mean difference of -1 days was observed
in patients receiving corticosteroid therapy.6
The effect of corticosteroids on mortality in patients
with community-acquired pneumonia remains unclear.
One retrospective observational study reported improved
mortality in patients with severe community-acquired
pneumonia who required catecholamines for shock treat-
ment.9 Assessment of adrenal function was not reported;
again, it is impossible to elucidate any difference from IDSA
guidelines.8 One meta-analysis suggests a possible mortality
reduction; however, this includes data from studies conducted
in 1956 and 1972, before many current medical advances.6
Subgroup analyses, which exclude these older studies,
provide stronger evidence for a mortality benefit in patients
with severe pneumonia; however, the disease severity is
widely defined. A more recent meta-analysis of nine studies,
including patients with mild and severe cases of community-
acquired pneumonia, did not find that corticosteroids had
a statistically significant effect on mortality.7 However, some
patient groups may benefit: a retrospective cohort study
found that treatment with systemic corticosteroids improved
mortality in patients with COPD who were admitted to
the ICU for community-acquired pneumonia.10
CLINICAL CONSIDERATIONS
Consider adjuvant corticosteroid therapy for the following
patients:
• those who require hospitalization or ICU admission for
community-acquired pneumonia
• those with severe community-acquired pneumonia as
determined by Pneumonia Severity Index or CURB-65
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2017 American Academy of Physician Assistants
Adjuvant steroid therapy in community-acquired pneumonia
score. The CURB-65 estimates pneumonia severity and
patient mortality risk by assigning one point for each of
the following: confusion, blood urea nitrogen greater than
19 mg/dL, respiratory rate of 30 or greater, systolic BP less
than 90 mm Hg or diastolic BP of 60 mm Hg or less, and
age of 65 years or older. Patients scoring 2 or more points
are at higher risk of death.
• those with severe community-acquired pneumonia requir-
ing vasopressors and who have an insufficient adrenal
response
• those with concomitant lung disease.10
Use caution when prescribing corticosteroids because of
their significant adverse reactions, including hyperglycemia,
immunocompromise, gastrointestinal (GI) bleeding, and
neuropsychiatric effects. Hyperglycemia requiring therapy
was the most commonly noted adverse reaction in one
study.4 Although the results did not suggest an increase in
GI bleeding, history of GI bleeding often was a study
exclusion criterion.4,6
Patients with asthma and COPD are at significant risk
of bronchospasm when they have a pulmonary infection.
The role of corticosteroid therapy in exacerbations of
COPD and asthma is well established. The Global Initia-
tive for Obstructive Lung Disease recommends a course
of systemic corticosteroids lasting no longer than 5 to 7
days for patients with COPD exacerbations.11 For patients
with asthma exacerbations, the ATS recommends 40 mg
to 80 mg of prednisone daily until the patient’s peak expi-
ratory flow reaches 70% predicted or personal best.12 A
variety of corticosteroid doses and durations of therapy
were assessed as adjuvant therapy for patients with com-
munity-acquired pneumonia. Further research is needed
to identify optimal agent, dosing, and duration for therapy
in this setting.
DISCUSSION
The Surviving Sepsis Campaign guidelines recommend
corticosteroids for patients with septic shock unrespon-
sive to both fluid resuscitation and vasopressors but
specifically recommends against their use when treating
sepsis in patients without shock.13 The authors state
“whether low-dose steroids have a preventive potency
in reducing the incidence of severe sepsis and septic shock
in critically ill patients cannot be answered.”13 This may
be reevaluated with evidence of improved outcomes with
the therapy.
Although no guidelines have been updated and evidence
for mortality benefit wavers, corticosteroid therapy has
several notable benefits for hospitalized patients, those
with pulmonary comorbidities, and those with higher
severity of illness. These benefits should be weighed care-
fully with the risks of corticosteroid therapy and the risk
to pregnant women. More research is needed to confirm
preliminary findings. The ESCAPe trial, which is assessing
the effect of corticosteroid therapy on mortality in critically
www.JAAPA.com 53
WHAT’S NEW IN INFECTIOUS DISEASES
ill patients with severe community-acquired pneumonia,
is expected to be completed in January 2018.14
LIMITATIONS
The growing body of research fails to address outpatient
treatment of community-acquired pneumonia with corti-
costeroids. Treatment of appropriate patients in the out-
patient setting is encouraged by the ATS/IDSA guidelines
and these patients represent a large portion of cases.
Additionally, despite the suggestion of improved outcomes
with this adjuvant therapy, no consensus exists on dosing,
agent, or duration.
CONCLUSION
Community-acquired pneumonia is common and carries
significant disease burden. Current guidelines recommend
adjunctive steroid therapy in certain patients with pneu-
monia and septic shock.12,13 Inpatient providers also may
consider adjuvant corticosteroid therapy in other patients
with community-acquired pneumonia, particularly those
with higher risk of complications. JAAPA
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