What Is A PCT Test: Antibiotic Stewardship Goals
The Greek word "sepo" means "I rot". The first mention of the word sepsis occurs in the poems of Homer.Although the mortality in sepsis has reduced from 50%-75% to a range of 30%-50% the incidence of sepsis has increased annually in the past forty years.This reduction in mortality is largely attributable to the discovery and use of antibiotics in the past hundred years of medicine.The total deaths sepsis causes is statistically similar to myocardial infarction.
Population: 2.4 to 3% incidence in general population.
ICU: 10-14% incidence in ICU patients.
ICU: 16% incidence in general population.
Brun-Buisson et al. JAMA 1995
S Todi et al. Crit Care 2007
Sands et al. JAMA 1997
Systemic Inflammatory Response Syndrome (SIRS):Not The Same As Sepsis
Systemic inflammatory response syndrome (SIRS) may occur in the absence of infection.
Two or more of the SIRS criteria are needed to document it-
- Temperature more than 380C (100.40F) or less than 360C (96.80F)
- Heart rate more than 90 beats/minute
- Respiratory rate more than 20 /min or PaCO2 < 32 mmHg
- White Blood Cell Count(WBC ) more than 12,000 cells/mm3, or 4,000 cells/mm3, or more than 10% immature (band) form of white blood cells.
So What Is Sepsis?
Systemic response to infection – It is confirmed or suspected infection plus 2 SIRS criteria.
Severe Sepsis –
Sepsis associated with organ dysfunction, hypo perfusion, or hypo tension
Septic Shock –
Severe Sepsis that cannot be resuscitated or stabilized with IV fluids alone.
So if you have fever, a fast heart rate, fast breathing and increased white blood cells you do not necessarily have sepsis because these can occur in the presence of systemic inflammatory response syndrome.For sepsis the presence of infection (either suspected or confirmed by microbial techniques) is necessary.So medical conditions like pancreatitis, burns, trauma may present with fever , tachycardia, tachypnea and increased white cell count either due to SIRS or Sepsis and there is no objective way to differentiate one from another.
What Is An Ideal Bio Marker?
A bio marker may be simply defined as a laboratory measurement that reflects the activity of a disease process.An ideal bio marker should not only help in the early diagnosis of a disease but also provide information regarding its severity and prognosis.Serial measurements of an ideal bio marker before and after the therapy should show decline to indicate the effectiveness of therapy.Erythrocyte Sedimentation Rate(ESR) is the oldest bio marker and is in use from the past ninety years.Other common bio marker is C reactive protein (CRP) which in use since the past 30 years.
Mortality In Sepsis
Why Do We Need A Bio Marker Like Procalcitonin?
A bio marker like procalcitonin may help differentiate SIRS from sepsis.This differentiation is of paramount importance because infection or sepsis would require antibiotics whereas inflammatory conditions do not require antibiotic treatment.A misdiagnosis may result in either cost escalation of treatment if antibiotics are administered to a person not suffering from sepsis whereas if antibiotics are delayed or denied in a patient of sepsis it will cause increased mortality or morbidity.So the best case scenario will be a bio marker which will objectively differentiate a infective cause of illness from a not infective one to guide the clinical decisions regarding antibiotic administration, thereby taking the guesswork out of the equation.
Procalcitonin (PCT) : A Prohormone
It is a protein composed of a chain of 116 aminoacids.It is a pro-hormone of calcitonin and is secreted from all parenchymal tissues in response to bacterial infection. Calcitonin on the other hand is secreted by the C cells of the thyroid only.The regulation of procalcitonin is by the CALC-1 gene located on chromosome 11.A bacterial infection increases the CALC-1 gene expression and stimulates the release of procalcitonin. The normal serum procalcitonin level is less than 0.05 ng/ml.
Procalcitonin Kinetics in Sepsis
Procalcitonin levels start increasing within three hours of infection and levels peak in blood at six to twelve hours after infection.It has a half life of around twenty four hours after which levels start declining.
Role of Procalcitonin In Clinical Practice
Assist in the diagnosis of sepsis
To monitor clinical course & therapy
Predict prognosis of disease
Procalcitonin :What Next?
Limitations of Procalcitonin As Biomarker
PCT may increase without sepsis
PCT may be normal in sepsis
New born less than 48 hours of birth
Bacterial Infection (If localized)
Early phase of sepsis
Medullary C-cell cancers of the thyroid
Pulmonary Small-Cell Carcinoma
Advantages over C Reactive Protein
Secretion begins after infection
Response to treatment
Effect of steroid & Non steriodal anti inflammatory drugs (NSAID’s)
To monitor clinical course & therapy
Significant reduction in antibiotic use
number of prescriptions and
duration of use
No impact on mortality, length of hospital stay
Arch Intern Med (2011); Clin Infect Dis (2011); Crit Care Med (2010); Infection (2009)
Systematic review and meta-analysis of procalcitonin guided antibiotic therapy
Good Antibiotic Stewardship
So procalcitonin may be used to assist in the more judicious use of antibiotics both inside and outside Intensive Care Units.A good antibiotic stewardship will prevent the emergence of multi drug resistance bacteria and help reduce the burden of sepsis.