Primary and secondary care doctors traditionally have relied on a combination of history, clinical examination, acute phase reactants such as ESR, CRP, leucocytosis (FBC), blood cultures, sputum and urine testing, to differentiate acute sepsis from other non-infective inflammatory conditions.
Routine haematological, biochemical, microbiological and radiological tests are relatively ‘non-specific’ and it is frequently difficult to ascertain a diagnosis and prognosis on the basis of currently available laboratory tests. This may result in unnecessary antibiotic treatment, and having started antibiotics it becomes difficult to monitor the dose and duration of treatment.
Shortcomings of current clinical assessment methods
Using current assessment methods, leucocytosis with acute gout can be mistaken for acute infection. ESR elevation due to paraproteinemia can be falsely interpreted as infection.
CRP elevation occurs with collagen vascular disease and inflammatory bowel disease. Consolidation on chest X-ray can be mistaken for pulmonary embolism and vice versa.
Indeterminate and equivocal results from current tests can impair decision making.
Procalcitonin as an indicator of invasive bacterial infection
Procalcitonin (PCT) is a prohormone with 116 amino acids, and the cleavage of this molecule yields calcitonin. The only recognised physiological activity of calcitonin is to lower serum calcium by suppression of bone resorption.1,2
However PCT shows a different biological activity and its synthesis and serum levels increase rapidly (within 4-6 hours) of invasion by pathogenic bacteria, fungi and malaria parasites.1,3 In contrast, PCT levels rarely increase in response to pure viral infection.4-6
Clinical applications of plasma PCT levels
Studies in the use of PCT in critical care, for establishing the mortality risk in critically ill septicaemic patients have been published.2,7 A maximum PCT level of 1-5 ng/ml correlates with a mortality of 11% and a maximum level of 51-100 ng/ml correlates with a 90-day mortality of 42%.1
These studies support the use of PCT as a biological marker of invasive bacterial infection. There are numerous publications that are beyond the scope of this review. However, the published studies provide cumulative evidence that plasma PCT levels rise rapidly in response to bacterial sepsis and rarely do so with viral infections or other non-infective inflammatory conditions.
GPs may find this bio-marker of bacterial infection to be very useful in the following day to day clinical scenarios:
- Differentiating acute gout from cellulitis
- Differentiating acute cellulitis from DVT
- Differentiating viral exacerbation of asthma from bacterial exacerbation
- Differentiating viral exacerbation of COPD from bacterial exacerbation.
A&E doctors may find PCT measurement useful in the following typical cases:
- Any seriously ill patient with suspected sepsis
- Any febrile patient without a known infection focus
- Any neutropenic patient on chemotherapy.
MAU and ITU practitioners may find PCT measurement useful in:
- Initiating antibiotics empirically and, more importantly, withdrawing antibiotics that have been started empirically
- Prognostication of mortality risk in critically ill patients
- Reinforcing intensive antibiotic treatment in patients with high PCT levels.
Procalcitonin is a reliable, consistently accurate biomarker of invasive bacterial infection with a high positive predictive value when plasma levels are elevated and a strong negative predictive value when plasma levels are low.
Viral infections, collagen vascular diseases, inflammatory bowel diseases and non-infective fevers do not cause plasma PCT elevation.
A targeted use of this new but well-established test can improve patient management, reduce antibiotic usage, encourage antibiotic withdrawal after they have been prescribed and help in prognostication and mortality risk assessment.
- Dr Ghurye is a GP on the Isle of Wight
|COMMON CLINICAL SCENARIOS|
|A PCT test may be useful in these situations:
|KEY LEARNING POINTS|
Key clinical points from published PCT literature
(Cautions/exclusions: Large burns, pancreatitis, bowel infarction and small cell lung cancer can lead to spurious increases of PCT)
|BLOOD LEVELS OF PCT AND MORTALITY|
Blood levels of PCT and 90 day mortality in critically ill patients:
- Gilbert DN. Use of plasma Procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010; 48 (7): 2325-9.
- Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection and sepsis: clinical utility and limitations. Crit Care Med 2008; 36: 941-52.
- Christ-Crain M, Muller B. Biomarkers in respiratory infections, diagnostic guides to antibiotic prescription,prognostic.markers and mediators. Eur Respir J 2007; 30: 556-73.
- Chua AP, Lee KH. Procalcitonin in severe acute Respiratory syndrome (SARS). J Infect 2004; 48: 303-6.
- Ingram PR, Inglis T, Moxon D, Speers D. Procalcitonin and C-reactive protein in severe H1NI influenza infection. Intensive Care Med 2010; 36: 528-32.
- Schultzle HJ, Forster A. Is serum procalcitonin a reliable diagnostic marker in children with acute respiratory tract infections. Eur J Paediat 2009; 168: 1117-24.
- Schuetz PM Christ-Crain M, Muller B. Biomarkers to improve diagnostic and prognostic accuracy in systemic infection. Current Opin Crit Care 2007; 13: 578-85.