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A Service Evaluation of Procalcitonin after
PRORATADaniel Cottle DICM
John Butler, Tony Dunne, Sanchia Pickering
Manchester Royal Infirmary 2011
Antimicrobial resistance in ICU
CPCMRSA
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
CalcitoninPCT
Müller B. et al., JCEM 2001
www.procalcitonin.com
Procalcitonin- Kinetics
Fast increase of PCT after bacterial challenge
• 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
Brunkhorst FM et alIntens Care Med 1998; 24:888-892
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
• Baseline data collection• Protocol• Introduction of protocol• Promote protocol• Reinforce protocol• Data collection• Analysis• Mean (standard deviation)• Student’s t-test
Exclusions
• Post bone marrow transplant• Pregnancy• TB, PCJ, toxoplasmosis• Neutropenia• Expected to die
Example Patient 38
1 2 3 4 5 6 70
5
10
15
20
25
0
50
100
150
200
250
300
350
WBC
PCT
CRP
Days
PCT
& W
BC
CRP
Date Clinical events Antibiotics CRP WBC PCT Microbiology culture
Temp Highest
or Lowest
Lactate 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
8/18/2011 Tazocin 49 12.1 0.53>80% Reduction y n
Results60 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 Chest Abdominal Others
Course length pre-
PCT8.6 (5.3)
Course length post
PCT6.5 (2.9)
Difference2.1 daysp=0.05
CI 0.0 - 4.2
Overall Chest Abdominal Others
Course length pre-
PCT8.6 (5.3)
Course length post
PCT6.5 (2.9)
Difference2.1 daysp=0.05
CI 0.0 - 4.2
Overall Chest Abdominal Others
Course length pre-
PCT8.6 (5.3) 7.7 (1.8)
Course length post
PCT6.5 (2.9) 5.5 (1.6)
Difference2.1 daysp=0.05
CI 0.0 - 4.2
2.2 daysp<0.0001 CI 1.2 – 2.8
Overall Chest Abdominal Others
Course length pre-
PCT8.6 (5.3) 7.7 (1.8)
Course length post
PCT6.5 (2.9) 5.5 (1.6)
Difference2.1 daysp=0.05
CI 0.0 - 4.2
2.2 daysp<0.0001 CI 1.2 – 2.8
Overall Chest Abdominal Others
Course length pre-
PCT8.6 (5.3) 7.7 (1.8) No data No data
Course length post
PCT6.5 (2.9) 5.5 (1.6) 7.9 6.0
Difference2.1 daysp=0.05
CI 0.0 - 4.2
2.2 daysp<0.0001 CI 1.2 – 2.8
Chest sepsis
• 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
• 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?