1. Procalcitonin

2. Objectives Review current data on procalcitonin Review its use at UCI MC

3. What is Procalcitonin? Precursor of hormone calcitonin Normally undetectable in healthy individuals Synthesized by thyroid C cells – Also released by liver, kidney, muscle, fat cells in response to bacterial toxins After exposure to toxins, serum levels of PCT increase within 2-4 hours, peaking ~14 hours (Kojic et al) – PCT may also be elevated in non-infectious conditions (trauma, surgical procedures, pancreatitis, renal impairment) (Kojic et al)

4. The Data on Procalcitonin Prospective, observational cohort study by Anand et al sought to determine role of procalcitonin (PCT) in differentiating culture-negative sepsis from non-infectious SIRS – Found that culture-negative sepsis patients had a significantly higher PCT relative to non-infectious SIRS patients Some studies suggest that PCT is not a helpful biomarker (Tang et al) – Sensitivity and specificity of 71% Heyland and colleagues reviewed 5 RCTs to evaluate the effect of PCT-guided antibiotic strategies on clinical and economic outcomes – Found that there was no effect of PCT-guided strategy on hospital mortality, ICU or overal hospital length of stay, however it may have reduced overall costs of care due to shortened duration of antibiotic administration Similarly, Christ-Crain and colleagues looked at PCT-guided therapy for management of lower respiratory tract infections – Found that PCT led to decreased use of antibiotics and no change in clinical outcome

5. Use of PCT at UCI MC Cost of PCT assay (self-pay): $35.45 PCT interpretation at UCI – <0.5 systemic infection not likely – 0.5-2.0 systemic infection possible, moderate risk of progressing to severe systemic infection – 2.0-10 systemic infection likely (unless other cause of inflammation is known), high risk of progressing to severe systemic infection – >10 major SIRS, almost always due to severe bacterial sepsis Chart-reviewed 15 ward patients – Reviewed PCT levels – Reviewed culture, imaging data – Reviewed antibiotic administration – Documentation of PCT use / impact on management

6. The Raw Data PtSIRS/Sepsis?PCTRadCxAbxDocumentation / Dx 1No<0.05YesNoYesOrdered – pneumonia 2Sepsis<0.05YesYes (G+) YesNo – endocarditis, joint 32 SIRS0.07NoYes (G-)YesNo – urine colonization? 41 SIRS0.09NoYes (G-)NoNo – asymp. bacteriuria 51 SIRS0.17No No – tumor pain 62 SIRS0.2No YesOrdered – UTI (UA neg) 72 SIRS0.23No No – sickle cell pain crisis 8Sepsis0.37YesYes (G-)YesNo – abscess 9SIRS0.87No No – aortic dissection 10SIRS  sepsis0.91NoYes (G-)YesNo – cholangitis 112 SIRS1.13?NoYesNo – CAP? 122 SIRS1.42No 13Sepsis1.45NoYes (G+) YesOrdered – CAP 14Sepsis4.33YesNoYesNo – CAP 151 SIRS7.07NoYes (G+) YesNo – septic joint

7. Some Observations PCT InterpNe/o InfectionAbx Not Likely85 (63%) Possible52 (40%)3 (60%) Likely22 (100%) Difficult to assess utility of PCT as there are no clear guidelines In our patients, 87% had PCT levels with low likelihood of infection, or possible infection – At UCI, no difference in antibiotic use in the “infection not likely” versus “infection possible” groups Never documented whether PCT had a role in clinical decision-making – Antibiotics were not discontinued based on a low PCT – Even if suspicion for infection was low, antibiotics were still given in some instances – Antibiotics were empirically given if a pt was thought to be septic

8. Conclusions This $35 test is sometimes used to determine the likelihood of infection at UCI MC However, it is not clear whether PCT levels have any impact on the decision to administer antibiotics – Documentation should be updated regarding PCT levels and their impact on management decisions – For those with elevated PCTs, trending PCT could be considered to determine duration of antibiotic administration

9. References Anand D, Das S, et al. Procalcitonin as a rapid diagnostic biomarker to differentiate between culture-negative bacterial sepsis and systemic inflammatory response syndrome: A prospective, observational, cohort study. J Crit Care 2015 Feb;30(1):218.e7-12. Christ-Crain M, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised single-blinded intervention trial. Lancet 2004;363:600-07. Heyland DK, Johnson AP, et al. Procalcitonin for reduced antibiotic exposure in the critical care setting: A systematic review and an economic evaluation. Crit Care Med 2011;39(7):1792-99. Kojic D, Siegler BH et al. Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis? World J Exp Med 2015 May 20;5(2):50-63. Tang BMP, Eslick GD, et al. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007;7:210-17.