Procalcitonin

Objectives

• Review current data on procalcitonin

• Review its use at UCI MC

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)

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

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

The Raw DataPt SIRS/

Sepsis?PCT Rad Cx Ab

xDocumentation / Dx

1 No <0.05

Yes No Yes Ordered – pneumonia

2 Sepsis <0.05

Yes Yes (G+)

Yes No – endocarditis, joint

3 2 SIRS 0.07 No Yes (G-)

Yes No – urine colonization?

4 1 SIRS 0.09 No Yes (G-)

No No – asymp. bacteriuria

5 1 SIRS 0.17 No No No No – tumor pain

6 2 SIRS 0.2 No No Yes Ordered – UTI (UA neg)

7 2 SIRS 0.23 No No No No – sickle cell pain crisis

8 Sepsis 0.37 Yes Yes (G-)

Yes No – abscess

9 SIRS 0.87 No No No No – aortic dissection

10 SIRS sepsis

0.91 No Yes (G-)

Yes No – cholangitis

11 2 SIRS 1.13 ? No Yes No – CAP?

12 2 SIRS 1.42 No No No No

13 Sepsis 1.45 No Yes (G+)

Yes Ordered – CAP

14 Sepsis 4.33 Yes No Yes No – CAP

15 1 SIRS 7.07 No Yes (G+)

Yes No – septic joint

Some ObservationsPCT Interp N e/o

InfectionAbx

Not Likely 8 5 (63%) 5 (63%)

Possible 5 2 (40%) 3 (60%)

Likely 2 2 (100%) 2 (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

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

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.