Procalcitonin

What it is. A 116-amino-acid precursor peptide of calcitonin, encoded by the CALC-1 gene. In health it is produced only by thyroid C cells and is completely cleaved to calcitonin, so circulating levels are negligible (<0.05 ng/mL). During bacterial infection, bacterial endotoxin and the cytokines IL-1β, TNF-α and IL-6 induce ubiquitous extrathyroidal CALC-1 expression in liver, lung, kidney, intestine and adipose tissue, releasing large amounts of intact, uncleaved procalcitonin into the blood.

Kinetics — why it is more useful than CRP. It rises within 2–4 hours, peaks at 12–24 hours, has a half-life of about 22–35 hours, and falls rapidly once the infection is controlled. CRP by contrast peaks only at 48 hours and falls slowly. This makes procalcitonin usable for early decisions and for serial trend interpretation.

The discriminating principle. Procalcitonin synthesis is suppressed by interferon-γ, which is released in viral infection — so it stays low in viral illness and rises in bacterial illness. This is the single concept the examiner wants. It is therefore more specific for bacterial infection than CRP, ESR or the white cell count, and its magnitude correlates with the extent of infection and with organ dysfunction, giving it prognostic value.

Interpretation thresholds. In suspected lower respiratory tract infection: <0.1 ng/mL — antibiotics strongly discouraged; 0.1–0.25 — discouraged; 0.25–0.5 — encouraged; >0.5 ng/mL — strongly encouraged. In the critically ill, >2 ng/mL suggests a high probability of severe sepsis or septic shock, and >10 ng/mL suggests overwhelming bacterial sepsis with organ failure. For monitoring, failure of the level to fall by 80%, or to below 0.5 ng/mL, by day 4 predicts a poor outcome.

Clinical uses. (i) Antimicrobial stewardship — procalcitonin-guided algorithms reduce antibiotic initiation and duration in lower respiratory tract infection and in ICU sepsis without increasing mortality. (ii) Differential diagnosis — helping separate bacterial pneumonia or bacteraemia from a COPD exacerbation, decompensated heart failure, viral illness or a non-infective inflammatory state. (iii) Prognostication and monitoring of response to treatment. (iv) Particular value in the older adult, in whom fever, leucocytosis and symptoms are all unreliable, and in whom CRP and ESR are often non-specifically raised by comorbidity.

Limitations — the marks are here. False positives: major surgery and trauma, burns, cardiac arrest and resuscitation, prolonged cardiogenic shock, severe pancreatitis, malaria, heat stroke, medullary thyroid carcinoma and small-cell lung cancer, end-stage renal disease and dialysis, and treatment with anti-thymocyte globulin or OKT3. False negatives: very early presentation (<6 hours), and localised or walled-off infection — abscess, empyema, infective endocarditis, osteomyelitis and septic arthritis — as well as intracellular and atypical organisms. It must therefore never be used alone to start or stop antibiotics; it supplements, but does not replace, clinical judgement and culture.

Recent randomised evidence — including the ADAPT-Sepsis and PRONTO trials and the NICE 2023 diagnostics guidance — has clarified exactly where procalcitonin adds value. It safely shortens antibiotic duration in ICU sepsis and in suspected lower respiratory tract infection, but it does not reduce mortality and does not reliably reduce antibiotic initiation in the emergency department. Current guidance therefore supports its use for guiding discontinuation and de-escalation rather than for deciding whether to start. In Indian public hospitals, where cost limits routine availability, this is the rational deployment — reserve it for de-escalation decisions in the ICU rather than as a screening test.