Procalcitonin A novel marker for systemic bacterial infections Presented By BRAHMS Diagnostica,LLC

1
ProcalcitoninA novel marker for systemic
bacterial infectionsPresented ByBRAHMS
Diagnostica,LLC
2
PCT Unmet diagnostic Need

• 500,000 new cases of sepsis per year in North
  America
• Sepsis develops in approximately 1 of
  hospitalized patients
• Sepsis mortality rate of 35 to 45
• New therapeutics near approval will require
  patient selection
• Established markers show poor differentiation
  between severe sepsis and other critical
  conditions

3
PCTClinical and Scientific Interest

• 450 papers
• 230 papers in Medline
• 100 Intensive Care Medicine
• 16 Transplantation
• 15 Pediatry
• 10 Neonatology
• 8 Surgery
• 6 Hematology
• PCT Monograph Thieme Publisher
• PCT Supplement Intens. Care Med

4
Experience with LUMItest PCT

• Assay for determination of the serum
  procalcitonin level biochemical and clinical
  evaluation
• Shimetani N Ohba Y Shimetani K Mashiko T
  Matsuyama N Ohtani H Morii M
• Department of Clinical Pathology, Koshigaya
  Hospital Dokkyo University School of Medicine,
  Koshigaya
• Rinsho Byori 2001 Jan49(1)56-60
• Among the patients with inflammatory disease who
  had a high CRP level, the PCT level was elevated
  only in those patients with severe bacterial
  infection. These results suggest that determining
  the PCT level may be useful in the differential
  diagnosis of severe bacterial infection. The
  patients who had a low CRP level, had a PCT
  level within the normal range. The patients with
  autoimmune disease, viral infection, and fungal
  infection did not have an elevated PCT level.

5
Experience with PCT-Q

• Procalcitonin strip test in the early detection
  of severe acute pancreatitis.
• Kylanpaa-Back ML Takala A Kemppainen E
  Puolakkainen P Haapiainen R Repo H
• Department of Surgery, Helsinki University
  Central Hospital, Finland
• Br J Surg 2001 Feb88(2)222-7
• CONCLUSION The PCT-Q test was a useful
  screening method for detecting severe acute
  pancreatitis. It is simple and quick to perform
  and, unlike currently available multiple factor
  scoring systems, can easily be adopted into
  routine clinical practice.

6
IRO-Concept in SepsisToronto Round table
meeting, 25/26 10.2000

• Proposed System
• IRO
• I Infection
• localized / systemic / necrotizing infection
• R Response
• biochemical markers
• mild / moderate
• inflammation
• O Organ dysfunction
• moderate MOF
• severe MOF

• Current System
• ACCP/SCCM
• Definition
• Infection
• Clinical signs of inflammation
• Fever, Tachycardia, Tachypnoe, Leukocytosis
• Organ dysfunction

7
Infection Response Organ dysfunction A new
sepsis concept

• Points
• PCT 9
• IL-6 9
• WBC 5
• HLA-DR 4
• Protein C 4
• CRP 3
• IL-10 3
• IL-8 3
• HMG-1 2
• D-Dimer 2
• e-Selectin 2

• Points
• Tissue factor 2
• TNF 2
• Thrombocytes 2
• Cholesterol 1
• Elastase 1
• C3a 1
• IL-1ra 1
• Thrombomodulin 1
• Neopterin 1
• Cortisol 1

80 possible sepsis biomarkers
8
Procalcitonin Key Facts

• PCT is the 116-amino acid prohormone of
  calcitonin selectively responds to systemic and
  septic infections.
• Early and reliable diagnosis.
• Increase in sepsis is not accompanied by an
  increase in calcitonin levels.
• An increase in PCT concentration can be detected
  in as little as 2 to 3 hours after the onset of
  septic infection.
• Easily measured by immunoassay.

9
Procalcitonin Biochemistry
1
57
60
91
116
96
cleavage by endopeptidases
10
Procalcitonin Reference Ranges
PCT (ng/mL)
Normal subjects lt0.5
Chronic inflammatory processes and autoimmune diseases lt0.5
Viral infections lt0.5
Mild to moderate localized bacterial infections lt0.5
SIRS, multiple trauma, burns 0.5 2
Severe bacterial infections, sepsis, multiple organ failure gt2 (often 10 100)
11
Indications for Use of PCT

• Monitoring patients at risk of systemic bacterial
  infection
• Assess severity of septic processes
• Prognosis response to therapy
• Assess Fever of Unknown Origin (FUO)

12
ROC comparison for discrimination between
bacterial (invasive and local) and viral
infections
Area under ROC Curve (95 confidence interval)
PCT 0.94 (0.90 to 0.96)
CRP 0.89 (0.85 to 0.92)
IL-6 0.78 (0.71 to 0.83)
13
CRP levels in pediatric patients on admission
with local bacterial infection, invasive
bacterial infection and viral infection
14
IL-6 levels in pediatric patients on admission
with local bacterial infection, invasive
bacterial infection and viral infection
15
PCT levels in pediatric patients on admission
with local bacterial infection, invasive
bacterial infection and viral infection
16
Measurement of Procalcitonin

• LUMItest PCT
• Quantitative coated tube format luminescent
  endpoint
• Requires a luminometer
• 100 tubes per kit
• 20 microliter plasma or serum sample
• PCT Q
• Semi-quantitative, membrane-based format
• Visual end-point, does not require an instrument
• 200 microliter plasma or serum sample

17
LUMItest PCT Procedure

• Add 20 µL standards, controls and sample to test
  tubes
• Add 250 µL tracer to test tubes
• Incubate 1 hour
• Wash tubes
• Read tubes in luminometer

18
PCT Q Procedure

• Add 6 drops or 200 µL plasma or serum to
  cartridge
• Incubate 30 minutes
• Read results

19
PCT Sales Growth Following Launch
20
PCT Sales Growth With Established Sales Base
21
Prospective use of PCT Reduction of hospital
stay for antibiotic treatments Cost savings
29.000 Euro/ 2 months

• PCT group
• 60 patients hospitalised for viral meningitis
• when PCT lt 0.5ng/ml AB treatment was stopped if
  no bacteriological or clinical suspicion for
  bacterial origin
• AB treatment 17/60 patients in emergency room
• 35 days hospital stay for AB treatment

• Control group
• 41 patients (1995-1996) hospitalised for viral
  meningitis
• Meningitis was considered viral if bacterial
  cultures were negative in day 4 and IFN-a or PCR
  was positive
• AB treatment 19/41 in emergency room
• 71 days hospital stay for antibiotic treatment

Menager C. et al. ESPID 26-28 March, Istanbul,
2001
22
Time on ICU / Costs of antibiotic treatment of
the ICU 1996/97 until 1999/2000 (Stüber, Uni
Bonn Sepsissymposium Jena, 16.2.2001
Costs of diagnostics 80 TDM Cost reduction AB
120 TDM Consolidated -40 TDM/ Year
23
www.procalcitonin.comwww.brahms.dehttp//bioanal
ytical.tripod.comEmail bionanalytical_at_datamarket
s.com.ar

• FAX [phone]
• Tel [phone]