ANNALS OF EMERGENCY MEDICINE
Systematic Review Snapshot
TAKE-HOME MESSAGE
The use of procalcitonin to guide antibiotic initiation or withdrawal in bacterial
infections may reduce overall exposure to antibiotics without affecting mortality.
However, further multicenter trials based in North America are needed before
widespread adoption of procalcitonin-guided algorithms.
METHODS
DATA SOURCES
EMBASE (1974 to 2011), MEDLINE
through PubMed and Ovid (1948
to 2011), the Cochrane Central
Register of Controlled Trials
(1991 to 2011), and online trial
registries were used to identify
eligible studies. Experts in the
field were contacted to identify
further eligible studies.
STUDY SELECTION
Randomized controlled trials in
adults with a diagnosis of respira-
tory tract infections or sepsis in
the emergency department (ED),
primary care, or ICU setting in
which the intervention used mea-
sured procalcitonin levels to in-
form decisions (guide initiation or
duration) of antibiotic therapy
compared with standard care.
DATA EXTRACTION AND
SYNTHESIS
Investigators independently ob-
tained data from the selected tri-
als by using a standardized data
abstraction tool. Results were
pooled and odds ratios with 95%
confidence intervals were calcu-
lated for overall mortality rates.
Antibiotic exposure and outcome
data were summarized and
grouped by clinical setting.
370 Annals of Emergency Medicine
Can Procalcitonin Levels Guide Antibiotic
Therapy in Bacterial Infections and Reduce
Antibiotic Overconsumption Without Having
a Negative Effect on Clinical Outcomes?
EBEM Commentators
John Pettey Sandifer, MD
Alan E. Jones, MD
Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS
Results
Pooled mortality outcomes.
Number
of
Patients, Mortality,
Group N No. (%)
All settings
Procalcitonin group 2,227 172 (7.7) 0.91 (0.73–1.14)
Control group 2,240 186 (8.3)
ED only
Procalcitonin group 1,214 63 (5.2) 0.95 (0.67–1.36)
Control group 1,235 67 (5.4)
Fourteen randomized controlled tri-
als met inclusion criteria, with a to-
tal of 4,467 patients. In both ED-
only studies and all clinical settings
combined, there was no difference
in mortality between the procalci-
tonin groups and the control groups
(Table). However, in both settings
there was an observed decrease in
either antibiotic initiation or dura-
tion of use. A sensitivity analysis in-
cluding the 3 trials deemed at low
risk for bias1-3 showed similar re-
sults with respect to mortality.
Commentary
Antibiotic overuse can expose patients
to adverse events and lead to increased
SEPTEMBER 2012
bacterial resistance. Although antibiot-
ics are the cornerstone to the treatment
of bacterial infections, efforts have
been made to identify patients who can
Odds Ratio (95%
be treated safely without antibiotics or
Confidence
Interval)
with a shorter duration of antibiotic
therapy. One approach has been to
measure serum biomarkers, such as
procalcitonin, which are released in re-
sponse to bacterial toxins and proin-
flammatory mediators and tailor antibi-
otic use according to these levels.
This systematic review includes 14
randomized controlled trials with a
total of 4,467 patients in primary
care, ED, and ICU settings. Initial pro-
calcitonin levels guided whether to
initiate antibiotics in the ED setting,
and decreasing levels of procalcitonin
were followed for cessation of antibi-
otics. A reduction in antibiotic use
was observed in all settings, mostly
because of lower prescription rates
for low-acuity infections (bronchitis
and chronic obstructive pulmonary
disease exacerbations treated on an
outpatient basis) and shorter duration
of therapy for sepsis and pneumonia
Volume , .  : September 

in the inpatient setting. None of the
trials individually or pooled demon-
strated a significant increase in mor-
tality. Another recent meta-analysis,
which evaluated 8 of the included 14
randomized controlled trials, evalu-
ated procalcitonin-guided therapy for
respiratory tract infections and re-
ported similar conclusions.4
The methodological quality of most
of the included trials was considered
to be low to moderate, and most of
the studies were conducted in Eu-
rope. Furthermore, outpatients in the
studies had close follow-up, which
may not always be attainable in cer-
tain US clinical settings. Two of the
included studies were authored by
one of the systematic review authors.
Further data are needed about long-
term mortality benefit, cost-effective-
ness, and procalcitonin-guided ther-
Volume , .  : September 
apy among low- to intermediate-risk
outpatients.5 The authors did, how-
ever, propose a framework of algo-
rithms that could be used in future
North American trials, which should
be conducted before procalcitonin-
based management of infections be-
comes routine.
Editor’s Note: This is a clinical synopsis, a
regular feature of the Annals’ Systematic
Review Snapshot (SRS) series. The source
for this systematic review snapshot is:
Schuetz P, Chiappa V, Matthias B, et al.
Procalcitonin algorithms for antibiotic
therapy decisions: a systematic review of
randomized controlled trials and recom-
mendations for clinical algorithms. Arch
Intern Med. 2011;171:1322-1331.
1. Briel M, Schuetz P, Mueller B, et al.
Procalcitonin-guided antibiotic use vs a
standard approach for acute respiratory
tract infections in primary care. Arch
Intern Med. 2008;168:2000-2007.
Systematic Review Snapshot
2. Schuetz P, Christ-Crain M, Thomann R, et
al; Pro-HOSP Study Group. Effect of
procalcitonin-based guidelines vs
standard guidelines on antibiotic use in
lower respiratory tract infections: the
ProHOSP randomized controlled trial.
JAMA. 2009;302:1059-1066.
3. Bouadama L, Luyt C-E, Tubach F, et al;
PRORATA Trial Group. Use of procalcitonin
to reduce patients’ exposure to
antibiotics in intensive care units
(PRORATA trial): a multicenter randomized
controlled trial. Lancet. 2010;375:463-
474.
4. Li H, Luo Y, Blackwell T, et al.
Procalcitonin-guided therapy in respiratory
tract infections: a meta-analysis and
systematic review. Antimicrob Agents
Chemother. 2011;55:5900-5906.
5. Yealy D, Fine M. Measurement of serum
procalcitonin. A step closer to tailored
care for respiratory infections? JAMA.
2009;302:1115-1116.
Michael Brown, MD, MSc, Alan Jones,
MD, and David Newman, MD, serve as
editors of the SRS series.
Annals of Emergency Medicine 371