1. A Service Evaluation of Procalcitonin after PRORATA Daniel Cottle DICM John Butler, Tony Dunne, Sanchia Pickering Manchester Royal Infirmary 2011

2. Antimicrobial resistance in ICU CPC MRSA

3. 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.

4. Procalcitonin Normally produced by the C-cells of the thyroid Normally undetectable Unknown role in sepsis Multiple sources in sepsis Analgesic

5. Procalcitonin – in relevant bacterial infection produced and released into circulation from the whole body Calcitonin in healthy personsPCT in bacterial infection Calcitonin PCT Müller B. et al., JCEM 2001 www.procalcitonin.com

6. 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

7. 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

8. Figure 3 Source: The Lancet 2010; 375:463-474 (DOI:10.1016/S0140-6736(09)61879-1)The Lancet 2010; 375:463-474 Terms and Conditions

9. Methods Baseline data collection Protocol Introduction of protocol Promote protocol Reinforce protocol Data collection Analysis Mean (standard deviation) Student’s t-test

11. Exclusions Post bone marrow transplant Pregnancy TB, PCJ, toxoplasmosis Neutropenia Expected to die

12. Example Patient 38 DateClinical eventsAntibioticsCRPWBCPCTMicrobiology culture Temp Highest or Lowest LactateVentilated Y/N Antibiotic Changes 8/12/2011 coamoxyclav, clari33114.215 y 8/13/2011 coamoxyclav, clari31020.811 y 8/14/2011 coamoxyclav, clari22519.56.5 y 8/15/2011 coamoxyclav, clari 13.43.2 y 8/16/2011 coamoxyclav, clari33111.4 yy 8/17/2011?chest sepsisTazocin5113.1 yn 8/18/2011 Tazocin4912.10.53>80% Reduction yn

13. Results 60 antibiotic episodes 8 to the ward 4 died 6 exclusions 42 analysed

14. 29 stopped early 8 no difference 1 escalated because 4 escalated despite

20. 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

21. Abdo sepsis Mean course length 7.9 days PRORATA: 8.1 days 4 escalated despite PCT 1 could have stopped earlier

22. 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?

23. QUESTIONS?