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?