Biomarkers in sepsis. Dr S Omar University of Witwatersrand CHBAH Bara ICU

Transcription

1 Biomarkers in sepsis Dr S Omar University of Witwatersrand CHBAH Bara ICU

2 Procalcitonin

3 PCT biomarker described as a sepsis associated protein Identical to the precursor protein of calcitonin which is produced by C cells in thyroid PCT bio produced by monocytes under specific conditions Gene responsible is CALC1 gene on chromosome 11p Same gene host of regulatory protein hormone precursors Procalcitonin-biochemistry and clinical diagnosis, M Meisner 2010

4 Circulatory monocytes don t produce significant PCT when stimulated by endotoxin Monocytes only produce PCT after stimulation if adherent to tissue

5 Biological effects of PCT Chemokine effect Modulates the release of proinflammatory cytokines Modulates inos induction vascular contraction effect Influences circulation and renal fxn Influence on mortality Experimentally in animal models, neutralizing PCT improves MAP, ph, renal fxn and mortality

6 Procalcitonin as a biomarker for bacterial infection and sepsis Sepsis: Life threatening OD resulting from a dysregulated host response to infection Gold standard for infection Blood culture Blood cultures are only positive in 30% Studies may therefore underestimate infection prevalence Appreciate the limitations of our knowledge regarding PCT and its use Sepsis-3 JAMA, 2016 Health Tech Assessment 2015, 19:35

7 PCT for bacteremia systematic review and meta-analysis Studies until June 2014 included Criteria: Adult, hospitilised,sepsis, confirmed bacteremia and PCT within 24 h 1567 articles 58 used in meta-analysis (3420 pt with bacteremia) 50 prospective 8 retrospective The diagnostic accuracy of procalcitonin for bacteremia: a systematic review and meta-analysis. Clin Microbial Infect 2015;21:

8 Dx ic Accuracy AUC: Fail Poor Fair Good Excellent

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10 ICU ED Prevalence 12% 8% Sensitivity 89% 76% Specificity 68% 68% FN are Low Great R/O

11 SAPS study: Efficacy and safety of PCT guidance in reducing theduration of A/B Rx in critically ill pts: RCT 15 Dutch ICU s with 1/3 of AB use vs US/UK 1575 pts enrolled largest study to date 761 PCT guided and 785- Std care 1 outcome A/B consumption 2 outcome Recurrent infections/los/a/b cost and PCT cost Evelien de Jong et al. Lancet infectious disease, 2016

12 A/B consumption PCT guided 761 Std care Duration of AB Rx 5 7 < AB free days in 1 st 28d P Mortality 28d 19.6% 25% year 34.8% 40.9% Adverse events Repeat AB 23% 22% 0.67 Recurrent infections 5% 2.9% 0.05

13 Costs PCT guided 761 Std care Median AB cost per pt P LOS (d) ICU In Hospital

14 How did they use PCT in the ICU Start A/B based on clinical grounds Measure PCT daily Advise stop A/B if PCT drops by 80% of peak or <0.5ug/L Physician could ignore advice (ignored in 50%)

15 Surprise mortality reduction A/B started preemptively if suspicious High PCT reassuring Low PCT earlier search for another cause and specific Rx contribute to mortality reduction Less A/B exposure Less toxicity Less A/B resistance Less C Diff

16 Prognostic value of PCT in pneumonia

17 Value for ICU (VAP) and ED(CAP) CURB65 score Confusion/ U>7/RR 30/ SBP<90 Score Mortalty (30d) % Rx strategy Outpatient 1 3 Outpatient 2 6 Admit 3 14 ICU 4/5 28 ICU Sensitivity = 0.62 cant R/O admission

18 PCT helps PCT threshold of 0.1ug/L Above this value CAP and VAP 4 fold increase in mortality Rx strategy - aggressive

19 Systematic review

20 Findings PCT effective and cost effective for: Guiding the discontinuation of A/B in adult ICU sepsis Initiation of A/B in adults presenting to ED with respiratory Sx s and suspected bacterial infection More Paediatric data required

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22 D. Antimicrobial Treatment 14. We suggest that measurement of PCT levels can be used to support shortening the duration of antimicrobial therapy in sepsis

23 10 key points for appropriate A/B use Antimicrobial stewardship and Resistance working group in International society of chemotherapy 1. Get appropriate Micro samples pre A/B 2. Avoid A/B to treat fever 30% infection 3. Start Empiric, and tailor local patterns 4. Optimise A/B dose, delivery and duration 5. Combo s -? 6. Avoid A/B with likelihood of promoting resistance 7. Source control 8. Deescalate ASAP 9. Stop sooner if safe 10. Team not alone PCT recommended here Hara et al. International Journal of antimicrobial agents,

24 Finally to your interest

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26 Retrospective case control

27 AUC 0.76 Sensitivity for Candidemia = 0.78 (reasonably good) At PCT >2.5ug/L NPV 98% i.e. R/O candidemia

28 Retrospective analysis of 171 episodes of sepsis and septic shock

29 Clearances in PCT and CRP to predict: Treatment failure 28 d mortality

30 Thank you

31 PCT[All Fields] AND ("critical illness"[mesh Terms] OR ("critical"[all Fields] AND "illness"[all Fields]) OR "critical illness"[all Fields] OR ("critically"[all Fields] AND "ill"[all Fields]) OR "critically ill"[all Fields]) May past 2 years serach