/clinical/,/clinical/cckm-tools/,/clinical/cckm-tools/content/,/clinical/cckm-tools/content/cpg/,/clinical/cckm-tools/content/cpg/laboratory/,

/clinical/cckm-tools/content/cpg/laboratory/name-97554-en.cckm

20170120

page

100

UWHC,UWMF,

Tools,

Clinical Hub,UW Health Clinical Tool Search,UW Health Clinical Tool Search,Clinical Practice Guidelines,Laboratory

Use of Procalcitonin Monitoring Related to the Diagnosis and Treatment of Respiratory Tract Infections and Emerging Sepsis - Adult - Inpatient

Use of Procalcitonin Monitoring Related to the Diagnosis and Treatment of Respiratory Tract Infections and Emerging Sepsis - Adult - Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Laboratory


Procalcitonin Monitoring Related to the Diagnosis and
Treatment of Respiratory Tract Infections and Emerging
Sepsis – Adult – Inpatient Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY .................................................................................................................................... 2
SCOPE ................................................................................................................................................................. 2
METHODOLOGY ................................................................................................................................................ 3
DEFINITIONS ...................................................................................................................................................... 8
INTRODUCTION ................................................................................................................................................. 8
RECOMMENDATIONS ....................................................................................................................................... 8
UW HEALTH IMPLEMENTATION .................................................................................................................. 13
APPENDIX A. EVIDENCE GRADING SCHEME .......................................................................................... 14
REFERENCES .................................................................................................................................................. 15
Contact for Content:
Lucas Schulz, PharmD, BCPS AQ-ID
Phone Number: 608-890-8617
Email Address: lschulz2@uwhealth.org
Contact for Changes:
Name: Name: Philip Trapskin, PharmD, BCPS
Phone Number: 608-263-1328
Email Address: ptrapskin@uwhealth.org
Guideline Authors:
Jason Bergsbaken, PharmD; Lucas Schulz, PharmD, BCPS AQ-ID
Coordinating Team Members:
Joshua Vanderloo, PharmD, BCPS, Drug Policy Program
Review Individuals/Bodies:
Derrick Chen, MD – Laboratory
Barry Fox, MD – Infectious Disease
Brian Sharp, MD, Jeff Pothof, MD – Emergency Department
Rob Hoffman, MD – Hospitalist
Jeffrey Wells, MD – TLC
Committee Approvals/Dates:
UW Antimicrobial Use Subcommittee: December 2016
UW P&T Committee: January 2017
Release Date: January 2017 Next Review Date: January 2018
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Executive Summary
Guideline Overview
1. Adult patients with a clinical suspicion of bacterial respiratory infection or sepsis warranting
antimicrobial initiation or adult patients who have been maintained on antimicrobial therapy and
may be candidates for de-escalation of therapy.
2. Immunocompromised hosts and other special populations were excluded from procalcitonin
studies and, therefore, PCT monitoring cannot be extrapolated to patients with the following
conditions: pregnancy, neutropenia, transplant patients with moderate to intense immune
suppression, chronic infections, and infections for which prolonged antibiotic therapy is the
standard of care (osteomyelitis, infective endocarditis).
3. PCT monitoring has not been evaluated in the diagnosis and management of most infectious
disease conditions, and those populations in #2.
4. PCT monitoring is NOT currently appropriate for use in the following conditions: pulmonary
aspiration syndromes, myocardial infarction patients with pulmonary infiltrates and/or
decompensated heart failure.

Key Revisions 2016 Periodic Review
1. No revisions were made to the document with the 2016 periodic review. The guideline was
simply reaffirmed as being safe to use as written.

Key Practice Recommendations
1. Procalcitonin monitoring is recommended for adult patients with a clinical suspicion for bacterial
respiratory tract infection according to Algorithm 1. (UWHealth Strong Recommendation,
Moderate Quality of Evidence).
2. Procalcitonin monitoring is reasonable during the evaluation of a patient with systemic
inflammatory response syndrome (SIRS) according to Algorithm 2. (UWHealth Strong
Recommendation, Low Quality of Evidence)
3. Procalcitonin monitoring should not replace standard diagnostic evaluation of the patient with
chronic obstructive pulmonary disease (COPD) and potential need for antibiotics (UWHealth
Strong Recommendation, Moderate Quality of Evidence); however, a value of < 0.25 µg/L and a
rapidly improving clinical status supports a non-bacterial infection etiology and antibiotic cessation
or modification is encouraged (UWHealth Strong Recommendation, Low Quality of Evidence).
See Algorithm 3.
4. Procalcitonin use in most infectious disease conditions, but especially pulmonary aspiration
syndromes, and myocardial infarction patients with pulmonary infiltrates and/or decompensated
heart failure is NOT recommended (UWHealth Strong Recommendation, Moderate Quality of
Evidence).

Companion Documents
ξ UWHC Lab Test Directory - Procalcitonin

Scope
Disease/Condition: Patients with suspected bacterial respiratory tract infection or emerging sepsis.

Clinical Specialty: Physicians and pharmacists

Objective: To provide guidance on the use of procalcitonin in managing patients with possible bacterial
infections

Target population:
Adult patients with a clinical suspicion of bacterial respiratory infection warranting antimicrobial initiation
or who have been maintained on antimicrobial therapy and may be candidates for de-escalation or
discontinuation of therapy. Adult patients with emerging bacterial sepsis. Other patients (COPD,
myocardial infarction, aspiration pneumonia) are addressed; however, the use of procalcitonin is not
recommended
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Major Outcomes Considered
ξ Proportion of positive and negative procalcitonin tests
ξ Deescalation/discontinuation of antibiotics with negative procalcitonin test

Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (PUBMED) were conducted by the guideline authors and workgroup
members to collect evidence for review. Expert opinion and clinical experience were also considered
during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external organizations and/or
arrived at a consensus through discussion of the literature and expert experience. All recommendations
endorsed or developed by the guideline workgroup were reviewed and approved by other stakeholders or
committees.

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Recommendations developed by external organizations maintained the evidence grade assigned within
the original source document and were adopted for use at UW Health.

Internally developed recommendations, or those adopted from external sources without an assigned
evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading
of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1 in
Appendix A).1

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme used within this document.

Recognition of Potential Health Care Disparities:
None identified.

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Algorithm 1. Adult patients with clinical suspicion for bacterial respiratory tract infection (excluding
COPD) without confounding alternative infectious conditions
Adult patients* with clinical suspicion for bacterial respiratory tract infection (excluding COPD)
without confounding alternative infectious conditions
Clinically stable
(primary care, ED, or inpatient setting with a presumed primary
respiratory infection)
Obtain PCT level
PCT level
< 0.25 µg/L

see Table 1
PCT level
≥ 0.25 µg/L
See Table 1
Antibiotic initiation
encouraged
b
Antibiotic initiation
discouraged
Clinical improvement
within 1-2 days
Absence of clinical
improvement within
24-48 hours
Do not recheck PCT
level; antibiotics
not indicated
Consider starting or
changing antibiotics,
assessing source control,
or a noninfectious etiology
Clinical improvement
within 72 hours
Repeat PCT level
PCT level ≥ 0.25 µg/L
PCT level < 0.25 µg/L or
drop by >80%
Antibiotic cessation
discouraged
Antibiotic cessation
encouraged
b
PCT should not be used in lieu
of standard diagnostic tests.
*EXCLUSION criteria: pregnancy, neutropenia, transplant recipients with moderate to intense immune suppression, or patients with
chronic infections, and infections for which prolonged antibiotic therapy is the standard of care (osteomyelitis, infective endocarditis)
PCT values are non-diagnostic in pulmonary aspiration syndromes, and myocardial infarction patients with pulmonary
infiltrates and/or decompensated heart failure.
Clinically unstable patients –
reference Algorithm 2
D
o

I

n
e
e
d

t
o

s
t
a
r
t

a
n
t
i
b
i
o
t
i
c
s
?
D
o

I

n
e
e
d

t
o

c
o
n
t
i
n
u
e

a
n
t
i
b
i
o
t
i
c
s
?
Continuation of antibiotics BEYOND the standard duration of therapy a specific ID condition (i.e.
CAP 8 days, VAP 8 days) is generally NOT RECOMMENDED
regardless of PCT value


Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Algorithm 2. Adult patients with systemic inflammatory response syndrome (SIRS) or sepsis
Empiric antibiotics ASAP recommended in septic shock with suspicion of
infection, regardless of PCT
Consider PCT level to evaluate for a non-infectious cause of SIRS
(high negative predictive value
) and to serve as baseline level to
assist in abx de-escalation
a
a = PCT monitoring should not delay antibiotic therapy
or determine initiation of antimicrobial therapy.
b = Consider continuing antibiotic therapy if patient is
clinically unstable due to suspected infectious source,
regardless of PCT level
Patient NOT improving clinically
at 48 hours
Patient clinically improving
at 48-72 hours
Consider changing antibiotics, assessing
source control, or a noninfectious etiology
Repeat PCT level NOT recommended
Repeat PCT level ONLY in patients with inconclusive
or absent microbiologic data to guide deescalation
or discontinuation
PCT level < 0.50 µg/L
or drop by >80%
PCT level ≥ 0.50 µg/L
Antibiotic cessation
encouraged
b
Antibiotic cessation discouraged
BUT antibiotic
DE-ESCALATION POSSIBLE
Repeat PCT level ONLY with significant
change in clinical status suggesting new or
worsening infectious cause
Continuation of antibiotics BEYOND the standard duration of therapy a specific
ID condition (i.e. CAP 8 days, VAP 8 days) is generally NOT RECOMMENDED
regardless of PCT value
PCT should not be
used in lieu of
standard diagnostic
tests.
Adult patients* with systemic inflammatory response syndrome (SIRS) or sepsis
*EXCLUSION criteria: pregnancy, neutropenia, transplant recipients with moderate to intense immune suppression, or patients with
chronic infections, and infections for which prolonged antibiotic therapy is the standard of care (osteomyelitis, infective endocarditis)
PCT values are non-diagnostic in pulmonary aspiration syndromes, and myocardial infarction patients with pulmonary
infiltrates and/or decompensated heart failure.

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Algorithm 3. Adult patients with clinical suspicion for bacterial respiratory tract infection with a history
of COPD
Adult patients* with clinical suspicion for bacterial respiratory tract infection
with a history of Chronic Obstructive Pulmonary Disease (COPD)
PCT level < 0.25 µg/L

see Table 1
PCT level ≥ 0.25 µg/L
See Table 1
PCT should not be used in lieu
of standard diagnostic tests.
*EXCLUSION criteria: pregnancy, neutropenia, transplant recipients with moderate to intense immune suppression, or patients with
chronic infections, and infections for which prolonged antibiotic therapy is the standard of care (osteomyelitis, infective endocarditis)
PCT values are non-diagnostic in pulmonary aspiration syndromes, and myocardial infarction patients with pulmonary
infiltrates and/or decompensated heart failure.
D
o

I

n
e
e
d

t
o

s
t
a
r
t

a
n
t
i
b
i
o
t
i
c
s
?
D
o

I

n
e
e
d

t
o

c
o
n
t
i
n
u
e

a
n
t
i
b
i
o
t
i
c
s
?
Continuation of antibiotics BEYOND the
standard duration of therapy a specific ID
condition (i.e. CAP 8 days, VAP 8 days) is
generally NOT RECOMMENDED
regardless of PCT value
Consider antibiotic therapy based on GOLD
guideline recommendations
Obtain PCT level and other diagnostic
laboratory tests*
* Standard Respiratory Diagnostic Laboratory Tests
a) respiratory viral panel
b) blood and sputum cultures
c) Streptococcus pneumoniae and Legionella urinary antigen
d) MRSA nasal and throat PCR (if anti-MRSA agents will be started)
Bacterial infection likely,
continue antibiotics
Bacterial infection unlikely -> correlate with
other diagnostic labs* and clinical scenario
Rapid clinical improvement and/or
NEGATIVE diagnostic labs*
Non-bacterial POSITIVE
diagnostic lab* finding
Antibiotic cessation
or modification
encouraged
b
Repeat procalcitonin monitoring is not
recommended for COPD patients

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Table 1. Procalcitonin (PCT) level evaluation for antibiotic initiation in clinically stable patients
with suspected respiratory tract infections without COPD in primary care, ED, or inpatient
settings2-13 (UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
Evaluation for antibiotic initiation in clinically stable patients with suspected LRTI without COPD in
primary care, emergency department, or inpatient settings
PCT level (µg/L) Antibiotic initiation When to consider overruling algorithm
<0.10 strongly discouraged
If patient becomes clinically unstable or has strong
evidence of bacterial pathogen
0.10-0.24 discouraged
0.25-0.49 encouraged
≥0.5 strongly encouraged


Table 2. Procalcitonin (PCT) level evaluation for antibiotic de-escalation in clinically stable
patients with suspected lower respiratory tract infections without COPD in primary care, ED, or
inpatient settings2-13 (UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
Evaluation for antibiotic de-escalation in clinically stable patients with suspected RTI without
COPD in primary care, emergency department, or inpatient settings
PCT level (µg/L) Antibiotic cessation When to consider overruling algorithm Serial PCT Monitoring
<0.10 or drop by
>90% strongly encouraged Consider continuing
antibiotic therapy if
patient clinically
unstable, regardless of
PCT level
Repeat PCT level only if
new or worsening respiratory
based infection
Consider initiation or
modification of antibiotic
therapy if no improvement in
PCT level
0.10-0.24 or drop
by >80% encouraged
0.25-0.49 discouraged
≥0.5 strongly discouraged


Table 3. Procalcitonin (PCT) level evaluation for antibiotic de-escalation in ICU patients with
suspected bacterial infections or sepsis2-4,11,14-27 (UWHealth Weak/Conditional Recommendation,
Moderate Quality of Evidence)
Evaluation for antibiotic de-escalation ICU patients with suspected bacterial infection or sepsis
PCT level (µg/L)
Antibiotic de-
escalation or
cessation
When to consider
overruling algorithm Follow-up
<0.25 or drop by
>90% strongly encouraged
Consider continuing
current antibiotic therapy
if patient clinically
unstable, regardless of
PCT level
Repeat PCT level in 48-72
hours with significant change in
clinical status suggesting new
or worsening infectious cause
Consider initiation or
modification of antibiotic
therapy if no improvement in
PCT level
0.25-0.49 or drop
by >80% encouraged
0.50-1.00 discouraged
>1.00 strongly discouraged



Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Definitions
1. Available PCT Assays28
1.1. Brahms PCT-Q assay (rapid PCT)
1.1.1. Semi-quantitative
1.1.2. Results in ~30 minutes
1.2. Brahms PCT LIA test (LUMItest PCT)
1.2.1. Standard assay for determining PCT levels in the plasma
1.2.2. Results in ~60 minutes
1.2.3. Analytical sensitivity of 0.1 µg/L and function sensitivity of 0.3 µg/L
1.2.4. Interassay variability between 9-82% when PCT values between 0.1-1 µg/L
1.2.4.1. Better assay for severe, systemic infections
1.3. Brahms PCT Kryptor
1.3.1. Most sensitive and highly precise plasma PCT measurement
1.3.2. Results in ~20 minutes
1.3.3. Analytical sensitivity of 0.02 µg/L and function sensitivity of 0.06 µg/L

Introduction
Biomarkers can serve as a helpful tool to differentiate bacterial infections from viral infections or non-
infectious inflammatory states. One such biomarker is procalcitonin (PCT), an amino acid precursor to
calcitonin. PCT is released as a component of the inflammatory cascade in response to bacterial
infections, and is a more sensitive and specific marker than other markers such as C-reactive protein.8
PCT levels rise to detectable levels within 3-6 hours of the onset of the inflammatory condition, peak at
12-48 hours, and fall rapidly during clinical recovery; levels increase with increasing infection
severity.2,8,29,30 PCT levels are usually not elevated in viral infections, most inflammatory conditions, or
following the use of corticosteroids or NSAIDs. However, PCT may be mildly elevated in some
inflammatory states such as malaria, pancreatitis, burn, traumatic injury, renal failure, or in post-
surgical patients.8

PCT monitoring may be used to guide antibiotic initiation and de-escalation for respiratory tract infections
(RTIs), reducing unnecessary antimicrobial exposure, length of stay, and total hospital cost.2,11 The
decision to initiate and deescalate antibiotics based on PCT values and clinical picture will be discussed
in this guideline.

PCT monitoring was included with a grade 2C recommendation in the 2012 update of the Surviving
Sepsis Guidelines as an option to assist the clinician in the discontinuation of empiric antibiotics in
patients who initially appear septic, but have no subsequent evidence of infection.31 Empiric antibiotic
therapy should not be withheld in the setting of sepsis and SIRS, but the use of PCT values to deescalate
antibiotic therapy in the clinically unstable or ICU patient will be discussed in this guideline.

PCT monitoring has been studied in patients with pulmonary aspiration syndromes32,33 and myocardial
infarction patients with pulmonary infiltrates34 and/or decompensated heart failure.35 The results of serum
procalcitonin monitoring in these conditions are not helpful in distinguishing bacterial infection from
alternative etiologies for decompensation.

Recommendations
1. General Recommendations
1.1. Procalcitonin (PCT) is a tool to differentiate bacterial from viral infections or non-infectious
inflammatory states and is useful when considering initiation of and de-escalation of
antimicrobial therapy in certain patient populations.2 (UWHealth Strong Recommendation, High
Quality of Evidence)
1.2. PCT levels ≤ 0.1 µg/L should exclude bacterial infection in most cases.2,8 (UWHealth Strong
Recommendation, High Quality of Evidence)
1.2.1. Procalcitonin levels are usually not elevated in viral infections, most inflammatory
conditions, or following the use of corticosteroids or NSAIDs.2,8
1.3. Procalcitonin can be mildly elevated in some inflammatory states such as malaria, pancreatitis,
burn, traumatic injury, renal failure, in post-surgical patients8, In patients with these conditions,
the use of procalcitonin to identify bacterial infection is not well established and is cautioned.
(UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

1.4. Procalcitonin may be variable and monitoring is not recommended in the following: pregnancy;
absolute neutropenia; immunocompromised states; chronic infections, and infections for which
prolonged antibiotic therapy is standard of care (e.g., infective endocarditis).36 (UWHealth Strong
Recommendation, High Quality of Evidence)
1.5. Procalcitonin monitoring has been studied in patients with pulmonary aspiration syndromes33,
myocardial infarction (with or without pulmonary infiltrates) and decompensated heart failure.34,35
The use of PCT in these clinical scenarios is NOT recommended. (UWHealth Strong
Recommendation, Moderate Quality of Evidence)
1.6. Procalcitonin monitoring is not recommended for detection of invasive fungal infections.37
(UWHealth Strong Recommendation, Moderate Quality of Evidence)
1.6.1. In a retrospective analysis of 55 episodes of invasive fungal infection, PCT was elevated
in less than 50% of the episodes.37 The sensitivity and specificity of PCT was low.
1.7. Monitoring of procalcitonin levels is useful as levels rise to detectable levels within 3-6 hours of
the onset of the inflammatory condition, peak at 12-48 hours, and fall rapidly during clinical
recovery.2,8,29,30 (UWHealth Strong Recommendation, High Quality of Evidence)
1.7.1. Levels of PCT have been shown to increase within 6 to 12 hours of the initial bacterial
infection, and circulating PCT levels are expected to decrease by half daily when the
infection is controlled by the host immune system and antibiotics.2,38
1.8. If PCT levels fail to start decreasing within 48-72 hours of treatment initiation, it is reasonable to
consider treatment failure and potential lack of source control. 23,30,39 (UWHealth Strong
Recommendation, Moderate Quality of Evidence)
1.9. Procalcitonin levels have not been studied as a tool to determine the admission or discharge
status of patient from the Emergency department. Procalcitonin level may have a lag of 6-12
hours. Therefore, procalcitonin values alone should not be used to determine the need for
admission or discharge of a patient from the Emergency department. (UWHealth Strong
Recommendation, Low Quality of Evidence)

2. Clinically stable patients with suspected respiratory tract infections without COPD in primary care,
ED, or inpatient settings2-10,12,13
2.1. When to order:
2.1.1. PCT measurement upon hospital or ED admission to determine antibiotic initiation is
reasonable to reduce unnecessary antibiotic exposure. 2-10,12,13 (UWHealth Strong
Recommendation, Moderate Quality of Evidence)
2.1.1.1. Levels of PCT have been shown to increase within 6 to 12 hours of the initial
bacterial infection.2,38
2.2. How to interpret:
2.2.1. Initiation of antibiotic therapy is not recommended if initial PCT level is less than 0.25
µg/L.2-10 (UWHealth Strong Recommendation, High Quality of Evidence), although in
patients with COPD, acute bacterial exacerbations are possible with levels lower than
0.25 and should be individualized40 (UWHealth Strong Recommendation, Moderate
Quality of Evidence)
2.2.1.1. Alternative diagnoses of viral infection and pulmonary embolism should be
considered in patients with an initial PCT level of less than 0.25 µg/L.2-10
(UWHealth Strong Recommendation, High Quality of Evidence)
2.2.2. Initiation of antibiotics is reasonable if PCT level increases to ≥0.25 µg/L.2 (UWHealth
Strong Recommendation, Moderate Quality of Evidence)
2.2.3. Recommendations for the use of PCT monitoring for the initiation of antibiotics in
clinically stable patients with suspected respiratory tract infections are listed in Table 1.2-
10
(UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)



Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

UWHealth Strong Recommendation, Moderate Quality of Evidence Table 1. Procalcitonin (PCT)
level evaluation for antibiotic initiation in clinically stable patients with suspected respiratory tract
infections without COPD in primary care, ED, or inpatient settings2-13 (UWHealth Weak/Conditional
Recommendation, Moderate Quality of Evidence)
Evaluation for antibiotic initiation in clinically stable patients with suspected LRTI without COPD in
primary care, emergency department, or inpatient settings
PCT level (µg/L) Antibiotic initiation When to consider overruling algorithm
<0.10 strongly discouraged
If patient becomes clinically unstable or has strong
evidence of bacterial pathogen
0.10-0.24 discouraged
0.25-0.49 encouraged
≥0.5 strongly encouraged

2.3. How to follow-up:
2.3.1. If antibiotics are held on admission:
2.3.1.1. Remeasurement of PCT is not recommended if patient demonstrates clinical or
symptom improvement within 1-2 days.2 (UWHealth Strong Recommendation,
High Quality of Evidence)
2.3.1.2. In cases with antibiotics are initially withheld, PCT levels should be rechecked in
12-48 hours when no clinical improvement is present and bacterial infection is
still in the differential diagnosis2-10 (UWHealth Strong Recommendation, High
Quality of Evidence)
2.3.2. If antibiotics are ordered on admission:
2.3.2.1. PCT levels can be effective every 48-72 hours to consider early cessation of
antibiotics.2-7 (UWHealth Strong Recommendation, Moderate Quality of
Evidence)
2.3.2.1.1. Repeat PCT monitoring at 48-72 hours is reasonable to reduce
antimicrobial prescription rates and duration of antimicrobial therapy
in patients with concern for respiratory tract infection.2-7,36 (UWHealth
Strong Recommendation, Moderate Quality of Evidence)
2.3.2.1.1.1. A systematic review of 8 studies including 3431
randomized hospitalized patients with suspected RTIs
showed a significant reduction in number of antibiotic
prescriptions (RR 0.69, 95%CI 0.55 to 0.88, P=0.03) and
duration of antibiotic use (SMD -1.27, 95%CI -1.26 to -
0.68, P<0.001) in patients with PCT-guided antibiotic
treatment compared to standard therapy.6 There was no
impact on mortality (RR 1.00, 95%CI 0.98 to 1.02,
p=0.912), admission to ICU (RR 0.78, 95%CI 0.57 to
1.08, p=0.727), or length of hospital stay between
groups (SMD -0.355, 95%CI -0.77 to 0.06, p=0.097).
2.3.2.1.1.2. A multicenter, noninferiority, randomized controlled trial
among 1359 patients in emergency departments of 6
tertiary care hospitals found a significant reduction in
mean duration of antibiotic use in a serial PCT
monitoring group (every 2 days) versus control group
(5.7 days versus 8.7 days, RRR -34.8%, 95%CI -40.3%
to 28.7%).3 The rate of overall adverse outcomes was
comparable in the PCT and control groups (15.4%
versus 18.9%).
2.3.2.2. The discontinuation of antibiotics is reasonable if the PCT level decreases to
less than 0.25 µg/L or by at least 80% of the peak value and patient is improved
clinically.2-7,11 (UWHealth Strong Recommendation, Moderate Quality of
Evidence)
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

2.3.2.3. Recommendations for the use of PCT monitoring to assist with determination of
antibiotic de-escalation in clinically stable patients with suspected respiratory
tract infections are listed in Table 2.2-10 (UWHealth Weak/Conditional
Recommendation, Moderate Quality of Evidence)

Table 2. Procalcitonin (PCT) level evaluation for antibiotic de-escalation in clinically stable
patients with suspected lower respiratory tract infections without COPD in primary care, ED, or
inpatient settings2-13 (UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
Evaluation for antibiotic de-escalation in clinically stable patients with suspected RTI without
COPD in primary care, emergency department, or inpatient settings
PCT level (µg/L) Antibiotic cessation When to consider overruling algorithm Serial PCT Monitoring
<0.10 or drop by
>90% strongly encouraged Consider continuing
antibiotic therapy if
patient clinically
unstable, regardless of
PCT level
Repeat PCT level only if
new or worsening respiratory
based infection
Consider initiation or
modification of antibiotic
therapy if no improvement in
PCT level
0.10-0.24 or drop
by >80% encouraged
0.25-0.49 discouraged
≥0.5 strongly discouraged

3. Clinically unstable or ICU patients with suspected bacterial infection or sepsis2,4,11,14-26
3.1. When to order:
3.1.1. Procalcitonin monitoring should not delay antibiotic therapy or determine initiation of
antimicrobial therapy.2,4,14-26 (UWHealth Strong Recommendation, High Quality of
Evidence)
3.1.2. Procalcitonin monitoring is reasonable in the initial patient evaluation to differentiate
sepsis from other non-infectious causes of a systemic inflammatory response to assist in
de-escalation of antibiotics later in hospitalization, despite mixed data to date.2,4,14-26
(UWHealth Strong Recommendation, Moderate Quality of Evidence)
3.1.2.1. A large systemic review of 3943 patients among 33 studies supports the use of
PCT as a diagnostic test for sepsis in critically ill adults post-surgery or trauma,
noting its superiority to C-reactive protein in determining presence of infection
supported by a greater global odds ratio for diagnosis of infection (15.7 versus
5.4, 95%CI 9.1 to 27.1).15
3.1.2.2. A systemic review and meta-analysis of 2097 patients among 18 studies
determined PCT levels cannot accurately differentiate sepsis for other non-
infectious causes of a systemic inflammatory response in critically ill adult
patients.17,18
3.1.3. Procalcitonin monitoring may be reasonable as a marker to help guide de-escalation of
antimicrobial therapy regardless of whether it was used to help guide the decision to
initiate antibiotic therapy.2,4,14-26 (UWHealth Weak/Conditional Recommendation,
Moderate Quality of Evidence)
3.2. How to interpret:
3.2.1. Empiric antibiotic therapy may be considered in patients with clinical suspicion for
infection who present with septic shock, regardless of PCT.2,4,14-26 (UWHealth Strong
Recommendation, High Quality of Evidence)
3.2.2. De-escalation of antibiotics may be considered if PCT levels decrease to less than 0.50
µg/L or by at least 80%-90% of the peak value and patient is improved clinically.2,4,14-26
(UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
3.3. How to follow-up:
3.3.1. Periodic monitoring of PCT levels may be considered in critically ill patients to assist with
cessation or de-escalation of antimicrobial therapy for suspected bacterial infections.2,4,14-
26
(UWHealth Weak/Conditional Recommendation, Moderate Quality of Evidence)
3.3.1.1. Three systematic reviews of 5, 6 and 7 trials, respectively, found PCT monitoring
resulted in a decrease in antimicrobial duration or exposure with no change in
mortality.21-23
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

3.3.1.2. In a large multicenter, randomized controlled open-label trial of 1200 patients,
there was no significant difference in death from any cause at day 28 between
the PCT and standard therapy group (31.5% versus 32.0%, RR 0.6%, 95%CI -
4.7% to 5.9%), however the PCT group had a significantly longer length of ICU
stay (6 days versus 5 days, p=0.004).19
3.3.2. It is reasonable to check PCT levels every 48-72 hours to consider de-escalation or early
cessation of antibiotics.2,4,14-26 (UWHealth Strong Recommendation, Moderate Quality of
Evidence)
3.3.3. If patient PCT levels do not respond to antibiotics within 48 hours and/or if the patient is
deteriorating clinically, it is reasonable to switch antibiotic therapy and/or consider source
control and a noninfectious workup.2,4,14-26 (UWHealth Strong Recommendation,
Moderate Quality of Evidence)
3.3.4. Recommendations for the use of PCT monitoring to assist with determination of antibiotic
de-escalation in ICU patients with suspected bacterial infections or sepsis are listed in
Table 3.2-4,11,14-27 (UWHealth Weak/Conditional Recommendation, Moderate Quality of
Evidence)

Table 3. Procalcitonin (PCT) level evaluation for antibiotic de-escalation in ICU patients with
suspected bacterial infections or sepsis2-4,11,14-27 (UWHealth Weak/Conditional Recommendation,
Moderate Quality of Evidence)
Evaluation for antibiotic de-escalation ICU patients with suspected bacterial infection or sepsis
PCT level (µg/L)
Antibiotic de-
escalation or
cessation
When to consider
overruling algorithm Follow-up
<0.25 or drop by
>90% strongly encouraged
Consider continuing
current antibiotic therapy
if patient clinically
unstable, regardless of
PCT level
Repeat PCT level in 48-72
hours with significant change in
clinical status suggesting new
or worsening infectious cause
Consider initiation or
modification of antibiotic
therapy if no improvement in
PCT level
0.25-0.49 or drop
by >80% encouraged
0.50-1.00 discouraged
>1.00 strongly discouraged


Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

UW Health Implementation
Potential Benefits:
ξ Antimicrobial stewardship through diagnostics-guided deescalation and escalation of antibiotics.
ξ Rapid identification of patient who may benefit from antibiotics.
ξ Implementation of procalcitonin monitoring may reduce unnecessary antibiotic exposure, reduce
ICU and hospital length of stay and reduce unnecessary admission to the hospital from the ED.

Potential Harms:
ξ Misinterpretation of the PCT value may result in inappropriate discontinuation of antibiotics.

Pertinent UW Health Policies & Procedures
None

Patient Resources
None

Guideline Metrics
None

Implementation Plan/Clinical Tools
1. Guideline will be posted on UConnect in a dedicated location for Clinical Practice Guidelines.
2. Content and hyperlinks within clinical tools, documents, or Health Link related to the guideline
recommendations (such as the following) will be reviewed for consistency and modified as
appropriate.

UW Health Guidelines
COPD – Adult – Inpatient/Ambulatory


Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of
patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a
clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit
the clinical condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.

Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

Appendix A. Evidence Grading Scheme
Figure 1. GRADE Methodology adapted by UW Health1


GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.





Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

References

1. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical practice guideline methodology
summit report: a report of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol. Jan 15 2013;61(2):213-265.
2. Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy
decisions: a systematic review of randomized controlled trials and recommendations for clinical
algorithms. Arch Intern Med. Vol 171. United States2011:1322-1331.
3. Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard
guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized
controlled trial. JAMA. Vol 302. United States2009:1059-1066.
4. Stolz D, Christ-Crain M, Bingisser R, et al. Antibiotic treatment of exacerbations of COPD: a
randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. Vol
131. United States2007:9-19.
5. Kristoffersen KB, Sogaard OS, Wejse C, et al. Antibiotic treatment interruption of suspected lower
respiratory tract infections based on a single procalcitonin measurement at hospital admission--a
randomized trial. Clin Microbiol Infect. Vol 15. France2009:481-487.
6. Li H, Luo YF, Blackwell TS, Xie CM. Meta-analysis and systematic review of procalcitonin-guided
therapy in respiratory tract infections. Antimicrob Agents Chemother. Vol 55. United
States2011:5900-5906.
7. Albrich WC, Dusemund F, Bucher B, et al. Effectiveness and safety of procalcitonin-guided
antibiotic therapy in lower respiratory tract infections in "real life": an international, multicenter
poststudy survey (ProREAL). Arch Intern Med. Vol 172. United States2012:715-722.
8. Fazili T, Endy T, Javaid W, Maskey M. Role of procalcitonin in guiding antibiotic therapy. Am J
Health Syst Pharm. Vol 69. United States2012:2057-2061.
9. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in
community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. Vol 174. United
States2006:84-93.
10. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on
antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded
intervention trial. Lancet. Vol 363. England2004:600-607.
11. Schuetz P, Litke A, Albrich WC, Mueller B. Blood biomarkers for personalized treatment and
patient management decisions in community-acquired pneumonia. Curr Opin Infect Dis. Vol 26.
United States2013:159-167.
12. 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. Vol 168. United
States2008:2000-2007; discussion 2007-2008.
13. Burkhardt O, Ewig S, Haagen U, et al. Procalcitonin guidance and reduction of antibiotic use in
acute respiratory tract infection. Eur Respir J. Vol 36. Switzerland2010:601-607.
14. Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic
treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. Vol 177.
United States2008:498-505.
15. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for
sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.
Crit Care Med. Jul 2006;34(7):1996-2003.
16. Layios N, Lambermont B, Canivet JL, et al. Procalcitonin usefulness for the initiation of antibiotic
treatment in intensive care unit patients. Crit Care Med. Vol 40. United States2012:2304-2309.
17. Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in
critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. Vol 7. United
States2007:210-217.
18. Luyt CE, Combes A, Reynaud C, et al. Usefulness of procalcitonin for the diagnosis of ventilator-
associated pneumonia. Intensive Care Med. Aug 2008;34(8):1434-1440.
19. Jensen JU, Hein L, Lundgren B, et al. Procalcitonin-guided interventions against infections to
increase early appropriate antibiotics and improve survival in the intensive care unit: a
randomized trial. Crit Care Med. Sep 2011;39(9):2048-2058.
20. Bouadma L, Luyt CE, Tubach F, et al. Use of procalcitonin to reduce patients' exposure to
antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.
Lancet. Vol 375. England: 2010 Elsevier Ltd; 2010:463-474.
Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org

21. Heyland DK, Johnson AP, Reynolds SC, Muscedere J. Procalcitonin for reduced antibiotic
exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care
Med. Jul 2011;39(7):1792-1799.
22. Kopterides P, Siempos, II, Tsangaris I, Tsantes A, Armaganidis A. Procalcitonin-guided
algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis
of randomized controlled trials. Crit Care Med. Nov 2010;38(11):2229-2241.
23. Agarwal R, Schwartz DN. Procalcitonin to guide duration of antimicrobial therapy in intensive care
units: a systematic review. Clin Infect Dis. Vol 53. United States2011:379-387.
24. Peters RP, Twisk JW, van Agtmael MA, Groeneveld AB. The role of procalcitonin in a decision
tree for prediction of bloodstream infection in febrile patients. Clin Microbiol Infect. Vol 12.
France2006:1207-1213.
25. de Kruif MD, Limper M, Gerritsen H, et al. Additional value of procalcitonin for diagnosis of
infection in patients with fever at the emergency department. Crit Care Med. Vol 38. United
States2010:457-463.
26. Ramirez P, Ferrer M, Marti V, et al. Inflammatory biomarkers and prediction for intensive care unit
admission in severe community-acquired pneumonia. Crit Care Med. Oct 2011;39(10):2211-
2217.
27. Schuetz P, Christ-Crain M, Muller B. Biomarkers to improve diagnostic and prognostic accuracy
in systemic infections. Curr Opin Crit Care. Vol 13. United States2007:578-585.
28. Foushee JA, Hope NH, Grace EE. Applying biomarkers to clinical practice: a guide for utilizing
procalcitonin assays. J Antimicrob Chemother. Vol 67. England2012:2560-2569.
29. Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and
sepsis: clinical utility and limitations. Crit Care Med. Vol 36. United States2008:941-952.
30. Gilbert DN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin
Microbiol. Vol 48. United States2010:2325-2329.
31. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for
management of severe sepsis and septic shock, 2012. Intensive Care Med. Feb 2013;39(2):165-
228.
32. Niederman MS. Distinguishing chemical pneumonitis from bacterial aspiration: still a clinical
determination. Crit. Care Med. Jun 2011;39(6):1543-1544.
33. El-Solh AA, Vora H, Knight PR, 3rd, Porhomayon J. Diagnostic use of serum procalcitonin levels
in pulmonary aspiration syndromes. Crit. Care Med. Jun 2011;39(6):1251-1256.
34. Remskar M, Horvat M, Hojker S, Noc M. Procalcitonin in patients with acute myocardial infarction.
Wien Klin Wochenschr. Mar 28 2002;114(5-6):205-210.
35. Kelly D, Khan SQ, Dhillon O, et al. Procalcitonin as a prognostic marker in patients with acute
myocardial infarction. Biomarkers. Jun 2010;15(4):325-331.
36. Procalcitonin-Guided Antibiotic Therapy
Comparative Effectiveness Review Summary Guides for Clinicians. Rockville MD2007.
37. Dornbusch HJ, Strenger V, Kerbl R, et al. Procalcitonin--a marker of invasive fungal infection?
Support Care Cancer. May 2005;13(5):343-346.
38. Lin T, Wang C, Cai XZ, et al. Comparison of clinical efficacy and safety between denosumab and
alendronate in postmenopausal women with osteoporosis: a meta-analysis. Int J Clin Pract. Apr
2012;66(4):399-408.
39. Bafadhel M, Clark TW, Reid C, et al. Procalcitonin and C-reactive protein in hospitalized adult
patients with community-acquired pneumonia or exacerbation of asthma or COPD. Chest. Vol
139. United States2011:1410-1418.
40. Falsey AR, Becker KL, Swinburne AJ, et al. Utility of serum procalcitonin values in patients with
acute exacerbations of chronic obstructive pulmonary disease: a cautionary note. Int J Chron
Obstruct Pulmon Dis. 2012;7:127-135.


Copyright © 2017 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 01/2017CCKM@uwhealth.org