PROCALCITONIN Evaluation & Use In Victoria, BC

PROCALCITONIN 

Evaluation & Use 

In Victoria, BC 

J Penman, MD 

30 th September 2010

CONTENTS 

SIRS, SEPSIS, PCT HISTORY & PHYSIOLOGY 

ASSAYS & INITIAL EVALUATION 

RESULTS OF PCT VERSUS CRP 

IMPLEMENTATION OF TESTING SERVICE 

LESSONS OF THE FIRST 6 MONTHS 

OTHER USES

SIRS & SEPSIS: 

SIRS Systemic Inflammatory Reaction 

Syndrome, Characterized by >2 of following 

Fever or hypothermia >38 or 90 beats / min 

Tachypnea >20 breaths / min or PaCO2 >32 torr 

Leucocytosis or leucopenia >12 or

HISTORY OF PCT 

Originally investigated as a marker for 

medullary thyroid cancer in the 1970s 

Relationship to sepsis found in the 1990s 

Desired to distinguish Sepsis from SIRS 

Advent of 1st automated assay (Brahms) 

Other assays developed (Brahms patent)

PHYSIOLOGY-1 

PCT is the precursor molecule of Calcitonin 

Calcitonin only secreted by thyroid C-cells and acts 

to increase blood calcium. 

All body cells can transcribe the CALCA gene 

Main triggers are G-ve lipopolysaccharides (LPS), 

G+ve cell wall antigens & bacterial toxins that react 

with Toll-like Receptors (TLRs) on cell surfaces. 

These cells secrete Procalcitonin, not calcitonin

PCT STRUCTURE 

PRODUCT OF THE CALCITONIN RELATED POLYPEPTIDE 

ALPHA GENE (CALCA) ON CHROMOSOME 11 (p15.2) 

PCT OF THYROID C-CELLS 116 AA LONG 

PCT OF OTHER CELLS 114 AA LONG

THYROID C-CELL

OTHER BODY CELLS

PHYSIOLOGY-2 

Stimulated by bacterial Products on TLRs 

Part of innate immunity - uncertain function 

Reports of added PCT worsening inflammation 

Reports of removal of PCT decreasing inflammation 

Increased levels detectable within 6h 

Half life 30h 

Without stimulus, drops 30-50% within 24h 

Disposal – Internal degradation, renal clearance 

is minor

PCT KINETICS

CONTENTS 






OTHER USES

AUTOMATED ASSAYS 

Brahms Kryptor CL immunoassays 

All other assays under license from Brahms 

Calibrated against Brahms standards 

Licensed by Brahms; patent holder on PCT 

Roche ECL immunoassay 

BioMerieux Vidas CL immunoassay 

Siemens Centaur CL immunoassay 

Diasorin Liason CL immunoassay

INITIAL EVALUATION 

Objectives: 

Evaluate VIDAS & Roche assays 

Compare PCT to CRP (our prev.marker) 

Process: 

Collected 22 suspect sepsis + 2 without SIRS 

PCT (both assays) & CRP daily for 2-4 days 

Results compared to culture & clinical 

information from patients’ charts

COBAS ACCURACY 

Apparatus: Roche Cobas e601 

Analyte: PROCALCITONIN 

Samples: PC PCT Level 1 & 2 (Roche QC)/VIDAS QC 1&2 Unit: ug/L 

Operator: Jennifer Annand Accuracy tolerance limit : 10.0% 

Level Sample Id Date Result 1 Result 2 Mean Result Assigned Deviation Accepted 

Mean (%) 

1 Vidas QC1 15-Jun-09 12.79 13.05 12.92 16.80 -23.1% NO 

2 Vidas QC2 15-Jun-09 1.40 1.43 1.42 1.79 -20.9% NO 

3 

4 PC PCT 1 15-Jun-09 0.494 0.486 0.49 0.48 2.1% YES 

5 PC PCT 2 15-Jun-09 9.80 9.88 9.84 9.69 1.5% YES 

Level Sample Id Date Result 1 Result 2 Mean Result Assigned 

Mean 

Deviation 

(%) 

Accepted 

1 Vidas QC1 16-Jun-09 12.85 12.88 12.87 16.80 -23.4% NO 

2 Vidas QC2 16-Jun-09 1.45 1.40 1.43 1.79 -20.4% NO 

3 FALSE 

4 PC PCT 1 16-Jun-09 0.477 0.485 0.48 0.48 0.2% YES 

5 PC PCT 2 16-Jun-09 9.71 9.82 9.77 9.69 0.8% YES

90 

80 

y = 0.8418x - 0.4055 

R² = 0.9949 

Roche e601 PCT (ug/L) 

70 

60 

50 

40 

30 

20 

10 

0 

0 10 20 30 40 50 60 70 80 90 

BioMerieux VIDAS PCT (ug/L) 

PCT Analytical-Systems Correlation between 

the Roche e601 and the BioMerieux VIDAS

ANALYZER SYSTEM METHOD MATRIX 

PCT 

ug/L 

Total 

Imprecision 

LLOQ 

ug/L 

BioMerieux VIDAS 

Chemiluminescence 

Monoclonal abs. 

Sandwich assay 

Vendor QC-1 15.28 2.91% 

BioMerieux VIDAS Vendor QC-2 1.76 3.56% 

0.09 

Roche Cobas e601 

Human Pl.-1 0.07 6.94% 

Electro-Chemi- 

Roche Cobas e601 

Luminescence 

Monoclonal abs. 

Human Pl.-2 4.86 1.35% 

Sandwich assay 

0.05-0.07 

Roche Cobas e601 Human Pl.-3 63.16 3.56% 

Table 1: Technology, precision and lower limit of quantitation of analyzer-systems

CONTENTS 






OTHER USES

12.00 

LEGEND: VIDAS v CRP; ROCHE v CRP 

10.00 

8.00 

PCT (ug/L) 

6.00 

4.00 

y = 0.0148x + 0.7489 

R² = 0.1824 

y = 0.0148x + 0.1715 

R² = 0.2746 

2.00 

0.00 

0.00 50.00 100.00 150.00 200.00 250.00 300.00 

CRPs (mg/L) 

Correlation of PCTs with CRPs for PCT

INITIAL PCT AND CRP RESULTS 

CULTURE RESULTS (N) 

INTIAL PCT 

RANGE (MEDIAN) 

INITIAL CRP 

RANGE (MEDIAN) 

BLOOD CULT POS (7) 0.44->100 (63) 23-341 (87) 

OTHER CULT POS (7) 0.13-45 (5.0) 136-253 (207) 

CULTURE ND/NEG (10)

BLOOD CULTURE POSITIVE CASES 

In 5/7 cases the CRP results do not correlate with PCT nor with clinical status or changes 

CASES 

VIDAS 

CLIN CORREL 

VIDAS 

PCT 

CRPs 

ROCHE 

PCT 

ROCHE 

CLIN CORREL 

CULTURE RESULTS 

CLINICAL 

CORRELATION 

SEPSIS 

RANGES 

BACTERIAL 

INFECTION 

A 

C 

H 

I 

L 

O 

R 

1.25 

1.48 

1.01 

0.93 

>100 

>100 

>100 

50.08 

0.45 

0.60 

0.79 

82.28 

85.73 

59.47 

37 

39 

52 

45 

32 

159 

246 

195 

23 

44 

54 

258 

309 

327 

0.708 

0.864 

BL: MRSA 

BL: MRSA 

Improved with Rx 

SEPTIC SHOCK >100 PRESENT 

SHOCK LIKELY >50102100 

BL:E.col 

Recovered on Rx 

POSSIBLE >0.50100 UNLIKELY 0.25 - 0.50 LIKELY 

75.93 ABSENT 0.10 - 100 

>100 

341 

353 

87 

118 

62 

62.97 

28.47 

>100 

>100 

>100 

BL:Listeria 

CSF:Listeria 

SP/UR:NG 

BL: E.coli 

UR:NG 

BL:MRSA 

SPT:MRSA 

BL:E.coli 

BL:E.coli 

BL:MSSA 

Remained Infected. Antibiotic changed 

after these results 

Discharged 2 days 

after last result 

Improved clinically & on CXR over this time 

Improved. Oral Rx subsequent 

Died in septic shock

PCT v OTHER MKRS 

SOFA = Sequential Organ Failure Assessment 

Brahms’ data: www.procalcitonin.com

CONTENTS 






OTHER USES

THE VALUE OF PCT 

Decision to treat with antibiotics: 

 

High negative predictive value (NPV) – ER Triage, 

Culture & treat / admit or discharge 

Wait 6-12h & repeat PCT / admit or discharge 

Monitoring Treatment 

 

PCT level tracks severity & progress – trend very useful 

Dropping 30-50% /d = successful Rx – continue 

Not dropping or increasing - change Rx, reculture 

Decision to stop antibiotics 

 

Unnecessary Rx is risky for patients and costly 

>90% drop from peak or

PCT & ABIOTIC Rx 


OTHER POSSIBLE VALUE 

Monitoring patients at high risk 

Patients on immunosuppressive therapy 

Neonates born after PROM, maternal GpB Strep+ve 

Post Surgical & post trauma patients 

Reduce need for CRP or Lactate in Sepsis 

CRP and lactate are not sepsis specific 

Many orders are based on monitoring sepsis 

response to treatment which is better done with PCT 

TAT for PCT better than CRP – not POC like Lactate

PCT CAVEATS 

Not for guiding antibiotic treatment in : 

Infections: endocarditis, osteomyelitis, 

CNS infs, deep-infections, Pseudomonas 

pneumonia. 

Organisms: Listeria, Legionella, PCP, 

Mycobacteria 

Immunosuppressed patients

IMPLEMENTATION 

3 month evaluation in SI - ICUs & ERs 

Reference Interval Adults 0.25-0.50 – Bacterial infection likely – rpt 6-24h 

>0.50-2.0 – Bacterial infection very likely . Moderate risk 

for sepsis 

>2.0 – Bacterial infection very likely. High risk for sepsis

CONTENTS 






OTHER USES

ACCEPTANCE OF TEST 

Generally good – some sceptics 

Not a silver bullet – better than CRP 

NPV and trend most useful of all 

Rapid uptake & sustained interest from 

ICU & ER 

Interest from NICU, Surgery & from upisland

ALGORITHM COMPLIANCE 

Criteria: 

Stop Rx & discharge sooner than Std of Care 

Order PCTs per algorithm 

Poor compliance with algorithm because: 

Decision levels too conservative (low) 

Algorithm & comments often conflict 

Cerner flags clear, comments not obvious

FALSE RESULTS 

False negatives not significant. High NPV 

False positives – i.e. not due to bact. inf. 

Ac.Pancreatitis, ext. burns, ext. lung damage 

Usually 80

NEXT STEPS 

Obtain an extension of clinical evaluation 

Revise the algorithm(s) 

Separate algorithms for ICU and ER 

Have regular case oriented discussions 

with users 

Evaluate the assay in other areas? NICU?

CONTENTS 






OTHER USES

NEONATAL SEPSIS 

Wealth of literature claims that PCT has 

similar value in NICU as in adult ICU 

Added value to monitor susceptible 

neonates, e.g. low birth weight prems, 

PROM cases, maternal GBS+ve 

Reference intervals in first 24h a problem

PCT v HRS AFTER BIRTH 


NEONATAL PROJECT 

Investigate physiological increase in PCT 

Relation to delivery – C/S v Vaginal 

Relation to GIT colonization 

Look at LBWP infants (

OTHER USES FOR PCT 

Prediction of renal disease (5) 

parenchymal involvement in pediatric UTIs 

Long-term morbidity in pediatric UTIs 

In vesico-ureteric reflux 

Severity of acute pancreatitis (2) 

Diagnosis & monitoring of post Sx Infs. (9) 

As an indicator of survival in the ICU

THANK YOU

KEY REFERENCES 

1. Mirjam Christ-Crain et al: Effect of procalcitonin-guided treatment on 

antibiotic use and outcome in lower respiratory tract infections: 

cluster randomised, single-blinded intervention trial. Lancet; Feb 21, 

2004, 363:600-607 

2. Vandack Nobre et al: Use of Procalcitonin to Shorten Antibiotic 

Treatment Duration in Septic Patients. Am J Respir Crit Care Med; 2008, 

177:498-505 

3. Philipp Schuetz et al: Effect of Procalcitonin-Based Guidelines vs 

Standard Guidelines on Antibiotic Use in Lower Respiratory Tract 

Infections (ProHOSP). JAMA; Sep 9, 2009, 302(10):1059-1066 

4. Jamie N. Deis et al: Procalcitonin as a Marker of Severe Bacterial 

Infection in Children in the Emergency Department. Ped Emerg Care; 

Jan 2010, 26: 51-60

PROCALCITONIN Evaluation & Use In Victoria, BC

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