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A Service Evaluation of
Procalcitonin after
PRORATA
Daniel Cottle DICM
John Butler, Tony Dunne, Sanchia Pickering
Manchester Royal Infirmary 2011
Antimicrobial resistance in ICU
CPC
MRSA
Antimicrobial resistance in ICU
• Major factor affecting
patient outcome and
resources.
• Insufficient infection
control measures.
• Selective antibiotic
pressure.
• Reducing antibiotic use
may contain the emergence
of multi-drug resistance
bacteria in ITUs.
• Stop inappropriate
prescribing.
• Shorten duration of
treatment of antibiotics.
Procalcitonin
• Normally produced by the C-cells of the
thyroid
• Normally undetectable
• Unknown role in sepsis
• Multiple sources in sepsis
• Analgesic
Procalcitonin –
in relevant bacterial infection produced and released into circulation
from the whole body
Calcitonin in healthy persons
PCT in bacterial infection
Calcitonin
Müller B. et al., JCEM 2001
www.procalcitonin.com
PCT
Procalcitonin- Kinetics
Fast increase of PCT after bacterial challenge
Brunkhorst FM et alIntens Care
Med 1998; 24:888-892
• Fast increase (after 3-4 hours), high dynamic range
• Wide concentration range < 0.05 ng/ml - 1000 ng/ml
• Short half-life time (~ 24 h) independent of renal function
• Easy to measure in serum and plasma - stable in vivo and in vitro
PRORATA Lancet 2010
• Multicentre, randomised, controlled trial.
• 311 procalcitonin, 319 control.
• Days without antibiotics:
– 14.3 days PCT : 11.6 control.
• The mean duration of the first episode of
antibiotics was reduced from 9.9 days to 6.1
days, AR 3.8 days; 95% CI 2.7-4.8, p<0.0001
• No increase in mortality
Figure 3
Source: The Lancet 2010; 375:463-474 (DOI:10.1016/S0140-6736(09)61879-1)
Terms and Conditions
Methods
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Baseline data collection
Protocol
Introduction of protocol
Promote protocol
Reinforce protocol
Data collection
Analysis
Mean (standard deviation)
Student’s t-test
Exclusions
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Post bone marrow transplant
Pregnancy
TB, PCJ, toxoplasmosis
Neutropenia
Expected to die
Example Patient 38
25
350
300
20
15
200
WBC
CRP
PCT & WBC
250
150
10
PCT
CRP
100
5
50
0
0
1
2
3
4
5
6
7
Days
Date
Clinical events
Antibiotics
CRP
WBC
PCT
Microbiology
culture
Temp
Lactate
Highest
or Lowest
Ventilated
Y/N
Antibiotic
Changes
8/12/2011
coamoxyclav, clari
331
14.2
15
y
8/13/2011
coamoxyclav, clari
310
20.8
11
y
8/14/2011
coamoxyclav, clari
225
19.5
6.5
y
8/15/2011
coamoxyclav, clari
13.4
3.2
y
8/16/2011
coamoxyclav, clari
33
11
1.4
y
y
8/17/2011?chest sepsis
Tazocin
51
13.1
y
n
Results
60 antibiotic episodes
8 to the ward
4 died
6 exclusions
42 analysed
42 analysed
29 stopped
early
8 no
difference
1
escalated
because
4
escalated
despite
Overall
Course
length prePCT
8.6 (5.3)
Course
length post
PCT
6.5 (2.9)
Difference
2.1 days
p=0.05
CI 0.0 - 4.2
Chest
Abdominal
Others
Overall
Course
length prePCT
8.6 (5.3)
Course
length post
PCT
6.5 (2.9)
Difference
2.1 days
p=0.05
CI 0.0 - 4.2
Chest
Abdominal
Others
Overall
Chest
Course
length prePCT
8.6 (5.3)
7.7 (1.8)
Course
length post
PCT
6.5 (2.9)
5.5 (1.6)
2.1 days
p=0.05
2.2 days
p<0.0001
CI 0.0 - 4.2
CI 1.2 – 2.8
Difference
Abdominal
Others
Overall
Chest
Course
length prePCT
8.6 (5.3)
7.7 (1.8)
Course
length post
PCT
6.5 (2.9)
5.5 (1.6)
2.1 days
p=0.05
2.2 days
p<0.0001
CI 0.0 - 4.2
CI 1.2 – 2.8
Difference
Abdominal
Others
Overall
Chest
Abdominal
Others
Course
length prePCT
8.6 (5.3)
7.7 (1.8)
No data
No data
Course
length post
PCT
6.5 (2.9)
5.5 (1.6)
7.9
6.0
2.1 days
p=0.05
2.2 days
p<0.0001
CI 0.0 - 4.2
CI 1.2 – 2.8
Difference
Chest sepsis
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Mean course length 5.5 days
PRORATA: CAP 5.5 days, VAP 7.7 days
8 had a starting PCT <0.5
3 could have stopped earlier
Abdo sepsis
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Mean course length 7.9 days
PRORATA: 8.1 days
4 escalated despite PCT
1 could have stopped earlier
Conclusions
• PCT reduced antibiotic use on our unit
• Definite end-point
• More structured approach
• Could this be reduced further?
• PCT <0.5 as a rule out?
QUESTIONS?