Procalcitonin for

Guidance of Antibiotic
Therapy in Pneumonia
Evidence Based Medicine
Mary Lewinski
May 20, 2010
 What determines duration of
treatment for CAP?
p Per IDSA guidelines:
n Antibiotics are indicated for the clinical
syndrome of pneumonia (fever, SOB,
cough/purulent sputum, elevated
WBC) + radiographic evidence +/-
culture data
n Treat for minimum 5 days; patient
should be afebrile for 48-72 hrs and
should have no more than 1 of the
following: T>37.8, P>100, R>24,
SBP<90, O2 sat<90% or PO2<60
mmHg on RA, AMS, vomiting.
 Procalcitonin
p Is both a precursor of calcitonin and a
cytokine mediator
p A marker of severe bacterial infections
n Correlation between severity of infection and
level of PCT
p Released in response to microbial toxins &
bacteria-specific proinflammatory
mediators (IL-1b, TNF-alpha, IL-6)
n Levels are attenuated by cytokines released
in response to viral infections (INF-gamma)
n True even in neutropenic patients
p Levels NOT affected by NSAIDs and steroids
n Unlike CRP and IL-6
 Procalcitonin - Kinetics
p PCT increases upon initial infection
within 6-12 hr
p Levels halve daily when the infection
is controlled
p PCT trend predicts the risk for
mortality
 Procalcitonin and Pneumonia
Severity

PSI = Pneumonia Severity Index; calculation includes age, sex, nursing home
residence, comorbidities, AMS, SBP<90, T <35 or >=40, RR>30, HR>125, and
lab/CXR findings.
 Caveats
p Procalcitonin may be elevated in the absence
of bacterial infection in situations of
massive stress: trauma, surgery,
hypothermia after cardiac arrest
n Levels are moderately elevated and decline
rapidly
p PCT may be falsely low very early in infection
or if the site is localized (abscess,
endocarditis, encapsulated empyema)
p Some atypical bacterial infections
(Mycoplasma) do not cause a significant
rise in PCT levels, while others (Legionella)
do
 Literature Review
p Question: Can procalcitonin-guided
therapy for pneumonia reduce
antibiotic usage without
compromising outcomes?
p Target population: Adults with
pneumonia
p Comparison: procalcitonin-guided
therapy vs. standard of care/clinical
judgment
p Search strategy: PubMed:
 Study Design
p Randomized, controlled trial involving patients
with CAP admitted from the ED (total 302
patients).
n Compared antibiotic therapy in pts treated according
to standard practice with those in whom PCT level
was used to guide therapy
n Excluded pts with CF, pulmonary TB, HCAP, immune
compromise
 Study Design
p For the Procalcitonin group, repeat levels
were drawn 6-24 hr later for patients
from whom antibiotics were withheld
n Levels were checked after 4, 6 and 8 d
and the cutoff points (or for those with
very high levels, a decrease to <10% of
initial level) were used to determine
whether abx would be discontinued
p Endpoints:
n Primary: total antibiotic use and duration
n Secondary: laboratory values and clinical
outcome
 Results
p There was
significantly
reduced antibiotics
exposure in PCT
group (from median
of 12 to 5d)
p All pts in whom
antibiotics were
withheld on
admission (15% of
PCT group and 1%
of control group)
had a favorable
outcome
 Study Design
p Multicenter, noninferiority, randomized
controlled trial in 6 EDs; 1359 patients
p Pts with lower respiratory tract infections
(bronchitis, COPD exacerbation, CAP) were
randomized to antibiotics given according
to PCT cutoff ranges vs. standard
guidelines.
n Excluded IVDU, severe immunosuppression,
life-threatening comorbidities, HCAP, pts on
chronic abx
p Outcomes: Noninferiority of composite
outcomes of death, ICU admission, disease-
specific complications or recurrent infection
requiring abx within 30 days.
n
Results
Results
p PCT guidance vs.
standard resulted in
similar rates of
adverse outcomes
(15.4% vs. 18.9%,
respectively) and
lower rates of
antibiotic exposure
and antibiotic-
associated
complications
(reduction of 8.2% in
PCT group).
p Length of hospital stay
was similar for both.
 Conclusions
p Procalcitonin level may be helpful in
distinguishing bacterial pneumonia
from respiratory infections of other
etiologies and thus inform the
decision to initiate antibiotics.
p PCT level can help determine when to
stop antibiotic therapy.
p PCT level correlates with disease
severity in many bacterial illnesses
studied.
 References
p Christ-Crain, M., et al. (2006). Procalcitonin
Guidance of Antibiotic Therapy in Community-
acquired Pneumonia. Am J Respir Crit Care
Med. 174: 84-93.
p Mandell, L.A., et al. (2007). IDSA/ATS Consensus
Guidelines on the Managemet of Community-
Acquired Pneumonia in Adults. CID. 44: S27-72.
p Schuez, P., et al. (2009). Effect of Procalcitonin-
Based Guidelines vs Standard Guidelines on
Antibiotic Use in Lower Respiratory Tract
Infections: The ProHOSPRandomized Controlled
Trial. JAMA. 302(10): 1059-1066.
p Schuetz, P., et al. (2010). Procalcitonin for
guidance of antibiotic therapy. Expert Rev Anti
Infect Ther. 8(5): 575-587.