Procalcitonin is an excellent biomarker for antibiotic use in bacterial infections alone. POCT guided PCT levels can help decide whether to add antibiotics or not in opd settings for respiratory tract infection.

1. Procalcitonin guided targeted
antibiotic therapy
Prof. Ashok Rattan,
MD, MAMS,
Common Wealth Fellow, INSA DFG Fellow, SEARO Temporary Advisor,
WHO Lab Director (CAREC/PAHO)
Advisor: Pathkind Labs Knowledge Forum, R & D and Quality

2. Acute Respiratory Tract Infection
• Most frequent cause for medical consultation
• Heterologous set of conditions:
• Upper respiratory Tract Infection
• Lower respiratory Tract Infection
• Acute Bronchitis
• Acute Lobar Pneumonia
• Acute exacerbation of COPD
• Community Acquired Pneumonia

4. Medico social impact of pneumonia
Medical Impact
• A frequent disorder 25 / 10,000
• More frequent in <5 & > 60 yrs
• Seasonality : winter
• High mortality: 5 th frequent
cause worldwide
• More in < 5 and > 60 yrs
• Frequent comorbidities
Social Impact
• Healthcare resources even in USA
• 10 million visits / year
• 600,000 hospitalization / year
• Quality of life
• 18th DALY
• D30 persistence of symptoms
• SF-36 long term changes
• Usual activities (d7 OPD; d21 IPD)
• Healthcare related costs
• OPD $ 2212; IPD $ 27,661
• Annual cost $ 17 billion

6. Levin M et al CMI 2018; 24: 1158

7. Diagnostic methods
Traditional
• 1. Sputum culture
• 2. Urine antigen
• S.pneumoniae
• L.pneumophila
• 3. Blood culture
• 4. X Ray Chest
Modern
• 1. RT PCR or
• 2. Multiplex PCR
• 3. Antigen detection
• 4. PCT
• 5. Culture of sputum
• 6. Blood culture
• 7. X Ray Chest
• 8. CT Chest

12. Antibiotic use Biomarker Wishlist
• Clinical outcome:
• 1. Better clinical decision making & 2. Better clinical outcome
• No negative effect on mortality
• Decrease in incidence of Clostidium difficle infection after antibiotic use
• Decrease is adverse drug event
• 2. Reduce cost:

15. Economic evaluation of procalcitonin-guided antibiotic
therapy in acute respiratory infections: a US health system
perspective Schuetz P et al Clin Chem Lab Med 2015; 53(4): 583–592

16. Is it Bacterial or Viral Infection ?

17. Procalcitonin guided targeted
antibiotic therapy
POCT Procalcitonin Quantitative
Iquant analyser by J Mitra SD Biosensor F 200 Manesar
Minividas by Biomerieux Wondfo Finecare

18. • 1.Kryptor (BRAHMS, Germany)
• 2. Atellica IM 1600 (Siemens)
• 3. Cobas e801 (Roche)
• 119 serum samples with PCT values < 5 ug/L (ng/ml)
• Medical Decision Points 0.25 and 0.5 ug/L (ng/ml)
• High correlation r2 = 0.97 and 0.99

20. Economic evaluation of procalcitonin-guided antibiotic
therapy in acute respiratory infections: a US health system
perspective Schuetz P et al Clin Chem Lab Med 2015; 53(4): 583–592
Unfortunately & Paradoxically this test
is NOT USED in India
Reason cited by some is
1. PCT is Too Costly
2. It is a sent out test & not POCT

21. • Infants < 90 day in ER were tested for PCT in ER during 5 months (n = 126)
• 14 (11.1%) were diagnosed with bacterial infection
• 4 (3.2%) had invasive bacterial infections
• POCT PCT had excellent diagnostic accuracy
• At an end point off 1 ng/ml, accuracy becomes 100%, specificity 92%

22. Performance characteristics of POCT PCT
• Precision (CLSI EP 5 A2): 6 samples containing 0.27, 0.61 1.30, 2.40,
5.48 & 9.12 ng/ml were tested over 10 days, 2 runs a day in 2
replicate, CV was calculated and should be < 10%
• Sensitivity (CLSI EP 17 A2): LOB, LOD, LOQ was 0.04; 0.11; 0.21 ng/ml
• Linearity: (CLSI EP 6A) eleven level linearity set was prepared by
mixing a pooled PCT spiked plasma containing 10.52 ng/ml linear
regression results were r2= 0.999; slope = 1.01
• Method comparison: (CLSI EP 9 A2): 40 serum samples were tested by
POCT and reference method. Linear regression r2= 0.98; slope = 0.99

23. • 60 pts had Salmonella Typhi isolated on blood culture by Bactec
• PCT before treatment ranged from 0.05 to 4 ng/ml
• Median PCT in confirmed typhoid cases was 0.22 ng/ml
• High PCT value was found only in severe sepsis (5%)
• PCT cannot be used as a specific biomarker for typhoid fever

24. • 189 cases of ricketsiosis were studied which included
• 115 cases of Q fever (60.8%)
• 55 cases of scrub typhus (28.1%)
• 19 cases of murine typhus (10.1%)
• Mean CRP in acute phase was 78.2 + 63.7 mg/l
• Mean PCT in acute phase was 1.05 + 1.40 ng/ml
• Only 10.8% had CRP levels > 150 mg/l
• Only14.2% had PCT levels > 2 ng/ml

26. • Charles et al (2006) retrospectic study of 50 nonsurgical patients with
positive blood culture: 35 bacteriemia & 15 candidemia
• Mean PCT level in patients with bacterimia was 9.75 ng/ml
• candemia 0.65 ng/ml
• PCT values > 5.5 ng/ml had NPV of 100% for candidimia.

27. What is Procalcitonin (PCT) ?
Schuetz P et al. BMJ Medicine 2011; 9: 107
• 116 amino acid precursor of calcitonin produced by Thyroid C cells &
Neuroendocrine cells of the lungs
• Calcitonin is involved in calcium homostasis, while procalcitonin is not
• Many other cells can produce PCT after specific stimulation but lack
enzyme to convert PCT  calcitonin
• Excessive production of PCT by many cells  rapid increase in blood
levels

29. Normal Secretion
Linscheid P et al. Endocrinology 2003; 144; 5578

30. In Healthy Individuals PCT level is very low as it is immediately
processed to CT

31. PCT in Bacterial Infection
Linscheid P et al. Endocrinology 2003; 144; 5578
1. Bacterial Infection (LPS) stimulates production of PCT from many somatic cells
2. These cells lack the enzymes to cleave PCT  calcitonin
3. PCT produced by these cells is rapidly released into blood stream
4. Cytokines produced during viral infection inhibit PCT production

32. Production of PCT is ubiquitous in Sepsis
Muller B et al. J Clin Endocrin Metab 2001; 86: 396
• 10 to 100 increase in calcitonin-1 gene
activation in sepsis
• More widespread than other common
cytokines like TNF α or IL- 6

34. Procalcitonin Rises Rapidly
Dandona J Clin Endocrinol Metab 1994; 79; 1605

35. Kinetics of PCT makes it a better biomarker of
bacterial infection
Simon J et al. Clin Infect Dis 2004; 19: 206

36. Specificity & sensitivity of PCT makes it a better biomarker than CRP, IL -6 & Lactate
Muller B et al. Crit Care 2000; 28:977; Simon L et al CID 2004; 39: 206

38. Serial measurement of PCT every 24 hours

39. Understanding Procalcitonin
• 1. Normal value is < 0.08 ng/mL [ug/L]
• 2. Elevated within 3 to 6 hours of bacterial infection
• 3. Peak in 6 to 12 hours
• 4. t ½ life is 24 to 30 hours
• 5. Cleared mainly by proteolysis
• 6. Some renal clearance
• 7. Maybe raised after major trauma / surgery
• 8. Not increased in Viral infections

42. Guidelines for Initiating antibiotics
PCT value (ng/mL)
PCT in ng/mL < 0.25 0.25 – 0.50 0.5 -- < 1 > 1
Antibiotic
initiation
Strongly
discouraged
Discouraged Encouraged Strongly
Encouraged

43. Guidelines for Stopping, continuing or
changing antibiotics
PCT value (ng/mL)
PCT in ng/mL < 0.25 > 0.25 – <0.50
Or
Decline of
>80% of peak
value
> 0.5
Or
Decline < 80%
of peak value
> 0.5
Or
Increase above
PCT Value
Antibiotic continuing
Strongly
discouraged
continuing
Discouraged
continuing
Encouraged
Changing or
Strongly
Encouraged

44. For diagnosis of sepsis it can be combined with
qSOFA

45. CRP guided use of PCT in Covid 19
Houghton R et al. medRxiv preprint
• Hypothesis: PCT < 0.5 ng/ml was associated with lower level of CRP
• 229 Covid-19 patients were studied
• CRP values below GM of entire patient population has a NPV for PCT < 0.5
of 97.6% at admission and NPV of 100% at 48 hours of admission
• CRP guided PCT testing algorithm can reduce cost & support
antimicrobial stewardship strategies in Covid-19

46. CRP guided use of PCT in Covid 19
Houghton R et al. medRxiv preprint
Baseline (at admission)
FN TP
TN FP

47. CRP guided use of PCT in Covid 19
Houghton R et al. medRxiv preprint
after 48 hours of admission
FN TP
TN FP

48. Where is the evidence ?

49. Procalcitonin-guided diagnosis and antibiotic
stewardship revisited Sager et al. BMC Medicine (2017) 15:15
• 1. Respiratory tract infections
• URTI
• Acute Bronchitis
• Acute execration of COPD
• Acute Lobar pneumonia
• 2. Sepsis
• 3. Abdominal infection, appendicitis, Acute pancreatitis
• 4. Endocariditis
• 5. Arthritis
• 6. UTI
• 7. Post operative infection
• 8. Neutropenia

53. High Serum Procalcitonin: Interpret with Caution
Khan, Clin Microbiol 2017, 6:2
• False elevated PCT values may occur in
• Severe stress following major surgery eg. Next day after Liver transplant
• Cardiac shock
• Autoimmune diseases
• Kawasaki’s disease
• Adult onset Still’s disease
• Medullary thyroid cancer
• Small cell lung cancer
• Cirrhosis of liver
• Pancreatitis
• PCT may not be elevated in
• Mycoplasma community acquired pneumonia
• Infected persons already on effective antibiotics

54. Vegetable peeler

64. Take home message
• PCT is the most specific of the commonly used biomarkers & has a
number of advantages over pervious markers
• It is not perfect
• Interpret PCT values in the context of clinical condition
• Serial measurements, atleast 24 hours apart, may be helpful
• Strength of evidence varies depending upon the type & site of infection
• Be aware of conditions which may affect PCT values
• Technical
• Biological
• Good clinical judgement should always be applies
(donot treat or not treat a number)

65. I
Thank you
For your attention
&
Action

66. Procalcitonin
> 0.5 ng/ml < 0.25 ng/ml