PROCALCITONIN

PROCALCITONIN: AN EARLY MARKER FOR
BACTERIAL SEPSIS-A STUDY OF 173

PAEDIATRIC ICU CASES.
INTRODUCTION
Procalcitonin (PCT) is an innovative and highly specific marker for the diagnosis
of clinically relevant bacterial infections and sepsis. Procalcitonin (PCT) supports early
diagnosis and clinical decision making which could direct an effective therapy at the right
time and save unnecessary spending for critically ill patients.
SEPSIS
Sepsis with acute organ dysfunction (severe sepsis) is the number one cause of
death in the non-coronary intensive care unit. Today, more than 750,000 Americans
develop severe sepsis each year equaling more than 2,000 new cases per day in the U.S.
alone while the worldwide toll is unknown. Cases of severe sepsis are expected to rise in
the future due to the increased awareness and sensitivity for the diagnosis, number of
immuno-compromised patients, use of invasive procedures, number of resistant
microorganisms, and the growth of the elderly population. Despite the enormous
investment in critical care resources, severe sepsis mortality ranges from 28% to 50% or
greater. The treatment of sepsis causes also enormous costs for the health care systems,
amounting to 2 billion U.S. dollars per annum in the U.S.A or 5 billion Euro in Germany
per annum. Both the medical and the health-economic problem of sepsis are in the focus
of the medical community. The intensive care specialists took the challenge to overcome
the current situation and to reduce sepsis mortality significantly by implementing
evidence-based clinical standards for diagnosis and treatment of sepsis worldwide.
IMMUNOLOGY OF SEPSIS
Sepsis, the systemic inflammatory response to infection, is considered the major

cause of death among critically ill patients in the developed world. While there is a
general view that this reflects contributions from both the pathogen and the host with
respect to an inappropriate inflammatory response, there is a lack of agreement as to the
key immune mechanisms. This has been reflected in the diverse range of
immunotherapies tested in clinical trials, often with rather marginal effects. The case has
been made for a pathogenic role of excessive immunity, the so-called cytokine storm ,
and for a role of too little immunity through immune paralysis. Apoptosis is implicated as
a key mechanism in both this immune paralysis and the multi-organ failure that is a
feature of severe sepsis. A number of polymorphisms have been implicated in
susceptibility to sepsis, including cytokine genes, HLA class II and caspase-12.
PCT AND SEPSIS
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The level of procalcitonin in blood can be used as an indicator for the diagnosis
and prognosis of sepsis in critically ill patients. PCT (procalcitonin) is indicated for use
primarily as a diagnostic parameter for bacterial infections triggering a systemic-
inflammatory reaction in the body (sepsis, septic shock). Local limited bacterial or organ-
related infections and capsulated abscesses induce a slight increase in PCT if at all.
Immunosuppression and neutropenia do not significantly affect PCT formation. Bacterial
toxins play a crucial role in the induction of PCT. Diseases, the etiology and course of
which involve bacterial endotoxins, such as sepsis, septic shock, systemic inflammation
and multiple organ dysfunction syndrome (MODS) are characterized by very high PCT
concentrations often ranging from 10 to 100 ng/ml and up to 1,000 ng/ml in
certain individual cases. Non-specific, i.e. infection-independent induction of PCT, may
occur after major surgery, multiple trauma or in newborn infants during the first days of
life. In these instances, values rarely exceed 5 ng/ml.
PCT induction and the increase in plasma levels are closely correlated with the
extent and type of systemic inflammation. Macrophages and monocytic cells of various
organs like liver synthesize and release PCT in response to bacterial infections. Both the
underlying disease and the anatomical extent of the infected tissue play a role. Once the
acute inflammation has waned, PCT concentrations rapidly fall. PCT can be used to
monitor therapy after surgical removal of a bacterial focus. Also in the course of septic
diseases, PCT reflects the severity of the disease and the course of the inflammatory
activity. Hence PCT is not only a monitoring marker in the course of sepsis, but also a
marker for the prognosis and success of therapeutic procedures. Elevated PCT plasma
levels
correlate with the course of severe septic diseases characterized by arterial hypotension
and impaired organ perfusion. PCT is therefore also an indicator of the severity of
systemic inflammation secondary to infection.
Because of these pathophysiological properties, PCT can be used for the

differential diagnosis of the etiology of acute inflammation. It can also be used as a
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marker with a broad range of infectious indications and for monitoring patients at risk of
sepsis or who are critically ill.
LEVEL OF PCT IN BLOOD
Normal level of PCT is <0.5ng/ml. It can increase up to 1000ng/ml.It increases in

patients with sepsis or septic shock. PCT>2ng/ml are highly suggestive of an infectious
process. PCT>10ng/ml is in patients with severe sepsis / septic shock. However patients
with PCT level between 0.5-2 ng/ml are said to be in an equivocal conditions which
neither confirm infection nor deny it. These cases may be due to other conditions that
include cases like ICU patients, post surgical patients, multiple trauma patients, patients
with extensive burns, new born infants, patients with viral infections or local infections or
autoimmune diseases, neoplastic diseases etc. PCT is detected 2-3 hrs post bacterial
infections. The level of PCT plateaus in 6-12 hrs; remains high for 48 hrs and falls to
baseline in the next 48 hrs. The half life of PCT in blood is 24 hrs.
NEED FOR PCT
In critically ill patients effective treatment need be given in shorter time to save
the life of the patient. Use of blood culture to determine the type of infection may take a
very long time (minimum of 48-72 hrs) which may prove fatal for the patient. Use of
PCT (which takes about 1hr 30 min) is a better option to save time and the patient. Also
the antibiotic prescribed for treatment can cost up to Rs.40, 000. If PCT turns out to be
negative, this money can be saved. This makes PCT a cost effective option.
BIOCHEMISTRY OF PROCALCITONIN
Procalcitonin is a 116 amino acid protein with a sequence identical to that of the
proharmone of calcitonin (32 amino acid). Under normal metabolic conditions,
hormonally active calcitonin is produced and secreted in the C-cells of the thyroid gland
after specific intracellular proteolytic procession of the proharmone procalcitonin. In
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severe bacterial infections and sepsis, however, intact procalcitonin is found in blood.
Current research indicates that the origin of procalcitonin in these conditions is extra
thyroidal.
PCT SYNTHESIS
C-cells of the thyroid are not believed to be the source of bacterial infection
induced PCT. Other cells including macrophages and monocytic cells of various organs,
e.g. the liver, are believed to be involved in the synthesis and release of PCT in response
to bacterial infections. It has been known for some time that synthesis of calcitonin
precursor mRNA takes place in the liver.
Calcitonin and its precursor peptides are synthesized by leukocytes and
neurocrine cells of internal organs such as the lung and the intestine as well as other cell
types. In fact, using in-situ hybridization, induced mRNA production was recently
detected in other cell types using the hamster as a model. Katacalcin and calcitonin were
detected intracellularly in various types of human leucocytes by means of flow-
cytometric analysis (FACS). Induced PCT mRNA was also observed in human
monocytic blood cells via semi-quantitative polymerase chain reaction (PCR) using the
reverse transcriptase technique (RT-PCR). It has not yet been confirmed whether the
quantities of PCT released by these cells are adequate to account for the levels of PCT
observed in septic patients. In addition to PCT, other cleavage products of the calcitonin
prohormone are found in plasma. However, PCT represents the main product of the
calcitonin precursor peptides.
ELIMINATION OF PCT
A Specific route of elimination for PCT has not been established. Like other
plasma proteins, PCT is probably degraded by proteolysis. Renal excretion of PCT plays
a minor role. Clinical data have shown that PCT does not accumulate in cases of severe
renal dysfunction. The fall in plasma PCT concentrations observed in patients with renal
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dysfunction does not differ significantly from that of subjects with normal renal function.
Approximately one-quarter of the concentrations measured in plasma are detected in
urine although the concentrations measured in urine fluctuate considerably. The renal
clearance of plasma PCT was calculated to be markedly less than 1ml/min. PCT could
also be detected in the ultra filtrate with continuous veno-venous hemofiltration or in the
dialysate with continuous hemodiafiltration. A sieving coefficient of 0.24 was recorded
for PCT. PCT clearance in plasma and ultrafiltrate ranged from 2 to over 5ml/min in
these studies. Filter adsorption phenomena were observed only during the first hour
following the onset of artificial renal replacement therapy. PCT plasma concentrations
were not significantly affected even during 24-hour hemofiltration or hemodiafiltration
the determination of PCT can therefore be used for diagnostic purposes in patients
presenting with renal failure or those receiving artificial renal replacement therapy.
THE EFFECT OF PCT ON CALCIUM AND PHOSPHATE CONCENTRATIONS
Evidence changes in serum calcium and phosphate levels were observed in only a
few individual studies in patients with elevated PCT concentrations. Slightly decreased
calcium levels and elevated phosphate levels were reported by Nylen et al. in patients
with pneumonia. No correlation between serum calcium and PCT could be established in
studies conducted in malarial patients. Laboratory animal studies in the hamster
confirmed a significant fall in serum calcium levels and an increase in serum phosphate
concentrations with simultaneous elevation of plasma levels of calcitonin precursor
proteins (including PCT) in a model of E.coli peritonitis. The role of PCT and other
calcitonin precursor molecules in these changes has not been confirmed.
SYNTHESIS OF PCT AND CALCITONIN
Synthesis of the proteins PCT and calcitonin is complex and starts with the
translation of a 141 amino acid precursor peptide (preprocalcitonin).
The “Pre-pro-hormone”:
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After transcription of the CALC-1 gene, the primary transcript is processed into
mRNA encoding a 141-amino acid protein with a molecular weight of approximately 16
kDa. This "precursor protein", preprocalcitonin, comprises a signal sequence, the N-
terminal region of procalcitonin (N-PCT), the middle sequence of calcitonin and the C-
terminal region of procalcitonin called "katacalcin".
PCT a glycoprotein:
The signal or leader sequence is a markedly hydrophobic sequence and mediates

binding of the protein to the endoplasmic reticulum (ER). The ER is the most important
structure of the cell for processing exocrine peptides. The signal sequence (AA 1-25) is
degraded immediately after location in the ER by an endopeptidase, EP. Precursor
proteins of calcitonin can be glycosylated and are more stable against enzymatic
degradation as glycoproteins than as asialoprotein. However, according to present
knowledge, inflammatory-induced plasma PCT is not glycosylated.
Specific proteolysis:
The resulting protein comprises 116 amino acids and is known as procalcitonin
(PCT, Fig: 1).Within this polypeptide, the amino acid sequence of calcitonin can be
found at position 60 to 91. This sequence is flanked by polybasic amino acids (Lys-Arg
and Gly-Lys-Lys-Arg). These sequences are signal sequences for specific proteolysis by
the enzyme prohormone convertase (PC), resulting in the main cleavage products of
procalcitonin: N-PCT (57 AA), calcitonin (32 AA) and katacalcin (21 AA) and their
combinations. This cleavage does not occur with inflammatory-induced PCT so that
intact PCT can be found in plasma. It is interesting to note that amino acid sequences
suitable for specific phosphorylation appear in the region between these cleavage
products. The potential for inflammation-activated phosphorylation of PCT may be
responsible for the presence of intact PCT in the plasma during sepsis and infection.
Recent studies have shown that the amino acid chain of PCT N-terminal can be truncated
by two amino acids (PCT 3-116) by the enzyme dipeptidyl peptidase IV. This does not,
however, affect the measurements recorded with the LUMItest PCT and BRAHMS PCT-
Q.
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The harmone calcitonin:
The hormone calcitonin does not take on its final form until immediately after this
cleavage process via cyclic formation of disulphide bridges (CysCys), cleavage of the C-
terminal glycine (AS 3, carboxypeptidase) and subsequent amidation (peptidyl glycine
amidating mono-oxygenase PAM). The hormone calcitonin is released into the
circulating blood in healthy subjects. Calcitonin has a half-life of only a few minutes in
blood.
THE GENE FAMILY OF CALCITONINS
At present, four genes with nucleotide sequence homologies corresponding to

calcitonin are known. These genes are collectively called the "calcitonin gene family",
but they do not all produce the peptide hormone calcitonin. The "CALC-1" gene is
responsible for the production of calcitonin and its precursor protein, procalcitonin. This
gene may be responsible for the generation of inflammatory induced PCT.
The calcitonin gene (CALC-I) exhibits one of the first examples of a process
termed alternative splicing. The primary RNA transcript is processed into different
mRNA segments by inclusion or exclusion of different exons as part of the primary
transcript. Calcitonin-encoding mRNA is the main product of CALC-I transcription in C-
cells of the thyroid, whereas CGRP-I mRNA (CGRP = calcitonin-gene-related peptide) is
produced in nervous tissue of the central and peripheral nervous systems.
A computer-aided analysis of the sequence of the CALC-I gene promoter region
known to date shows that, at least theoretically, different transcription factors activated
by inflammation bind in this region and may influence transcription. Reporter gene
construction could help to clarify the inflammatory-activated induction of PCT.
The primary transcript of the CALC-I gene produces 5 exons which can be
combined to form three different mRNAs after transcription, maturation, splicing and
polyadenylation. The resulting mRNA CT-1 and CT-2 encode preprocalcitonin and differ
only in the sequence of the carboxyterminal peptide I and II. In the third mRNA
sequence, the calcitonin sequence is lost and alternatively the sequence of CGRP is
encoded in the mRNA. CGRP is a markedly vasoactive peptide with vasodilatative
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properties. CGRP has no effect on calcium and phosphate metabolism and is synthesised
predominantly in nerve cells related to smooth muscle cells of the blood vessels.
ProCGRP and PCT have partly identical N-terminal amino acid sequences.
Additional post-transcriptional processing can occur so that PCT is expressed
with additional mRNA products and their corresponding translation products.
PCT IN THE DIFFERENTIAL DIAGNOSIS OF VIRAL AND BACTERIAL

INFECTIONS
In disorders triggered solely by viral pathogens, the body reacts with only a slight
increase in PCT values if at all. PCT can therefore be used for the differential diagnosis
of viral versus bacterial infections provided that systemic inflammation accompanies the
bacterial infection. Differential diagnosis is therefore significant in cases where a rapid
decision between bacterial and non-bacterial etiology of the infection has therapeutic
consequences. Gendrel et al. could detect significant differences in PCT concentrations in
establishing viral versus bacterial etiology in children with meningitis. In these cases,
PCT was used as an early and sensitive indicator of bacterial-induced meningitis.
Differential diagnosis of viral and bacterial infections is also relevant in immunodeficient
or immunosuppressed patients, i.e. in transplantation medicine, in neutropenic patients
and following chemotherapy.
THE DIFFENTIAL DIAGNOSIS OF VIRAL AND BACTERIAL MENINGITIS
Markedly increased plasma PCT concentrations were detected in children

presenting with acute bacterial as opposed to viral meningitis. The parameter can be used
to confirm rapid diagnosis of bacterial versus viral meningitis.
HIV INFECTION (AIDS)
Increased PCT values were not found even in the advanced stages of disease in
HIV-positive patients. In the presence of sepsis, however, PCT induction was observed,
even in HIV infections. Secondary infections in the form of Pneumocystis carinii-induced
pneumonia (PCP), cerebral toxoplasmosis, tuberculosis, viral infections or local bacterial
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or fungal infections do not trigger an increase in PCT concentrations in HIV-infected
patients provided that these are organ-related or local infections without systemic
inflammation .
THE PROGNOSTIC VALUE OF PCT
One of the most important indications for determination of PCT is monitoring the
course of systemically active infections and their prognostic evaluation. PCT reflects the
extent of systemic inflammation secondary to infection. In cases of severe infection, the
course of inflammatory factors together with the potential onset of progressive organ
failure generally determines patient prognosis. PCT values quickly fall once the acute
inflammation has waned whereas plasma levels fail to return to normal in the case of
persistent systemic inflammation secondary to infection. PCT can therefore be used to
assess the prognosis in patients with sepsis and multiple organ dysfunction syndrome and
to follow up the surgical removal of a focus of infection or monitor the conservative
treatment of an infection. Increasing or persistently high PCT values indicate ongoing
inflammatory disease activity and suggest a poor prognosis. Declining values indicate a
diminishing inflammatory reaction, successful removal of the infectious focus and thus a
favorable prognosis. Increasing or decreasing PCT values can therefore be crucial in
deciding whether or not further diagnostic procedures are required and for modifying or
confirming therapeutic interventions. Determination of PCT has economic consequences
as well. Further diagnostic procedures can be dispensed with following the surgical
removal of an infectious focus if PCT values fall rapidly after surgery whereas
unchanged, high values indicate that additional diagnostic procedures should be
conducted and a new therapeutic approach or alternative procedure should be considered.
PCT FOLLOWING REMOVAL OF FOCUS
Once a bacterial focus has been removed, normal PCT values indicate that a
generalized infection is no longer present and that systemic inflammation is under
control. A residual local bacterial focus cannot, however, be ruled out. Antibiotic therapy
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or further surgical procedures may therefore be required until no further clinical signs of
infection are apparent.
CLINICAL COURSE ASSESSMENT VIA PCT LEVELS
The course of PCT values during sepsis reflects the increasing or decreasing
systemic immune reaction of the body. PCT values often run parallel with the patient's
clinical condition and give early confirmation of a successful therapy or improvement in
the patient's disease. In many cases, a rapid decline in elevated PCT values towards
normal levels is associated with an improvement in the clinical condition. On the other
hand, if PCT values change only slightly over time or remain at a pathological level (e.g.
>2ng/ml), then this finding is generally synonymous with the on-going critical condition
of the patient. In fatal outcomes, PCT values often rise prior to the final stage.
SPECIAL FEATURES DURING AN ACUTE CLINICAL COURSE
During an acute course, it should be noted that at high PCT values, i.e. during an
episode of marked PCT induction, levels must naturally fall. This initial drop in very high
PCT levels should not be overestimated. The course of PCT values should thus be
monitored over several days.
SPECIAL FEATURES OF A PROLONGED CLINICAL COURSE
In some patients, a prolonged clinical course is characterized by low, albeit

above-normal and occasionally declining PCT values with little or no change in the
clinical condition of the patient. Typically only minor inflammation is evident in these
patients. In such cases, a bacterial or inflammatory focus may also be present. Low PCT
values can therefore indicate general exhaustion of the immune system ("PAID", post-
aggression immunologic depression) and down regulation of the immune system. In these
cases, on-going treatment should be specific and clinically orientated.
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LITERATURE REVIEW
Procalcitonin as a marker of severity in septic shock:

To evaluate the prognostic value in septic shock, PCT levels were repeatedly
determined and compared with tumour necrosis factor-α (TNF-α)- and interleukin (IL)-6
bioactivity as well as with C-reactive protein (CRP) serum levels. Serum levels of TNF-
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(WEHI 164) and IL-6 (B13–29 subclone 9) bioactivity, CRP and PCT were determined
on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock. Survivors and non-
survivors were comparable in terms of age and severity of sepsis characterized by the
APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were
peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no
significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and
remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP
was constantly elevated with no difference between the groups. In non-survivors PCT
remained increased, while the course of survivors was characterized by decreased values
which were significantly lower (P<0.05) at every time point compared with those patients
who died. A significant correlation could be found on day 1 (P<0.05) and at the end of
the observation period (P<0.01) when comparing PCT levels with the multiple-organ-
failure score. PCT seems to be a more reliable prognostic parameter in septic shock than
IL-6, while TNF and CRP did not show any difference between survivors and non-
survivors. These data indicate that PCT may represent a valuable parameter not only in
the diagnosis of sepsis but also in the clinical course of the disease (Schroder et al.,
1999).
Pre-emptive antibiotic treatment vs ‘standard’ treatment in patients with elevated

serum procalcitonin levels after elective colorectal surgery: a prospective
randomised pilot study:
The aim of this study was to investigate (a) whether PCT could serve as a
negative predictive marker for postoperative complications and (b) whether, in patients
with elevated PCT levels, a pre-emptive treatment with the third-generation
cephalosporin ceftriaxone is superior to an antibiotic treatment starting later on the
appearance of clinical signs and symptoms of infection. By screening 250 patients with
colorectal surgery, 20 patients with PCT serum levels more than 1.5ng/ml on at least 2 of
the first 3 postoperative days were identified. The remaining 230 patients were followed-
up for the occurrence of infectious complications. The 20 patients with elevated PCT
were included in a prospective randomised pilot study comparing pre-emptive antibiotic
treatment with ceftriaxone vs standard treatment. The negative predictive value of PCT
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for systemic infectious complications was 98.3%. In patients receiving pre-emptive
antibiotic treatment (ceftriaxone), both the incidence and the severity of postoperative
systemic infections were significantly lower compared to those in a control group. Major
differences were also observed with respect to duration of antibiotic treatment and length
of hospital stay. PCT is an early marker for systemic infectious complications after
colorectal surgery with a high negative predictive value. A significant reduction in the
rate of postoperative infections in patients with elevated PCT serum concentrations was
achieved by means of pre-emptive antibiotic treatment (Chromic et al., 2006).
Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in

early diagnosis of sepsis:
Quantitation of neutrophil CD64 expression and procalcitonin (PCT) levels in

blood samples have been recently proposed as useful tools for early detection of sepsis.
To determine the usefulness of these tests, blood samples of 112 patients were analyzed,
admitted to an intensive care unit (ICU), presenting clinical symptoms of sepsis, as well
as of 50 healthy controls. At the end of the study, a retrospective analysis showed that
only 52 of the 112 ICU-patients presented a real sepsis (positive blood culture). The
results obtained indicated that of the 52 patients with sepsis, 50 and 49 presented levels of
neutrophil CD64 expression ≥ 2398 molecules per cell (cut-off determined by
receiver operator characteristic analysis) and PCT levels 〉 0.5 ng/ml (cut-off
suggested by the manufacturer), respectively. However, the neutrophil CD64 test showed
higher specificity in detecting sepsis since 5 out of the 60 ICU-patients without sepsis
(negative blood culture), presented CD64 expression levels ≥ 2398 molecules
per cell, PCT levels ≥ 0.5 ng/ml were shown in 27 patients. Moreover, while
none of the 50 healthy controls presented a neutrophil CD64 level higher than the cut-off
value, 5 patients presented PCT levels ≥ 0.5 ng/ml. In conclusion, the data seem
to indicate that the quantitation of CD64 expression could be taken into consideration as a
sensitive and specific test for early diagnosis of sepsis (Cardelli. et al., 2008).
Procalcitonin in the early diagnosis of nosocomial sepsis in preterm neonates:
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The diagnostic usefulness of procalcitonin (PCT), C-reactive protein and
immature to total neutrophil ratio (I : T) in nosocomial sepsis among neonates treated in
an intensive care unit were examined in this study. A retrospective analysis and
comparison of diagnostic utility performed in preterm neonates using receiver operating
characteristic curves for the diagnosis of culture-proven sepsis. A total of 78 clinically
suspected sepsis episodes in 73 newborns were analysed. The median values of PCT
were: 0.56ng/mL (interquartile range (IQR) 0.33-1.32) in group with aseptic blood
culture (n = 15), 2.69 ng/mL (IQR 1.10-5.29) in Gram-positive (n = 47) and 9.36ng/mL
(IQR 3.11-39.35) in Gram-negative sepsis (n = 16). Only PCT values were significantly
different (P < 0.01) among all groups. This was also true when correction for differences
in blood withdrawal time was implemented. The positive and negative predictive values
of PCT in the diagnosis of sepsis equalled 97.5% and 88.9%, respectively, for a cut-off
value of 0.99 ng/mL. PCT was significantly better in diagnosis of sepsis than I : T (P =
0.03). No other significant differences in diagnostic efficacy were noted. The diagnostic
efficacy was the highest for measurements made two or more hours since the onset of
symptoms. The PCT serum concentration is a valuable tool for early detection of
nosocomial sepsis in infants. Highest levels of PCT were observed in Gram-negative
infections (Fendler et al., 2008).
Prospective evaluation of procalcitonin in sepsis in the Illawarra area of Australia:

PEPSIA study:
Procalcitonin (PCT) is a precursor of the hormone calcitonin and has been

proposed as a marker of infection in critically ill patients. The role of procalcitonin in the
early detection of sepsis in an Australian intensive care-high dependency unit
(ICU/HDU) was evaluated. This prospective observational study enrolled 204
consecutive patients admitted to the ICU/HDU of Wollongong Hospital, NSW, over a 3-
month period, October to December 2001. Of the 204, 172 (84%) were included in the
final analysis. Patient demographic data, serum PCT levels and the vital signs required to
score the criteria for systemic inflammatory response syndrome (SIRS) and sepsis were
recorded daily until the patient left the ICU. Cultures were obtained when clinically
indicated. PCT measurement appears a useful screening test for sepsis with a cut-off
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value > 0.85 ng/dL. At levels >10 ng/dL, its diagnostic accuracy improves significantly.
PCT level was able to discriminate between sepsis and nonsepsis, and between septic
shock and non-septic shock. However, it failed to discriminate well between bacterial and
non-bacterial SIRS with a 95% CI for area under the receiver operating characteristic
curve of 0.59-0.76. The use of PCT as a screening test (PCT >0.85ng/dL) in conjunction
with traditional criteria is of value in the early diagnosis of bacterial sepsis in suspected
cases in the ICU. PCT appears to be a reliable diagnostic test for bacterial sepsis at levels
> 10 ng/dL (Muthiah et al., 2007).
Inflammatory Markers in SIRS, Sepsis and Septic Shock:
Despite great advancement in the understanding of the pathophysiology and in the

development of novel therapeutic approaches, mortality of sepsis still remains
unacceptably high. Adequate laboratory diagnostics represents a major requirement for
the improvement of this situation. For a better understanding of the immunological
dysregulation in this disease, several markers are now available for routine diagnostics in
the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin
and the LPS-binding protein (LBP). These novel markers will be compared to the
conventional procedure of diagnosing inflammatory and infectious disease, such as
measurements of C-reactive protein (CRP) as a major acute phase protein and differential
blood counting. Important questions addressed in this review are the usefulness of these
markers for early diagnosis, their role as prognostic markers and in the risk assessment of
patients. Furthermore, we will discuss whether these parameters are to differentiate
between systemic inflammatory response syndrome (SIRS) and sepsis at its different
degrees. In the case of an infectious nature of the disease, it is important to differentiate
between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies.
The literature was analysed with focus on the evidence for diagnostic and analytical
performance. For this purpose international definition and staging criteria were used in
context of criteria for assay performance including sensitivity, specificity, negative and
positive predictive values, ROC analysis and other analytical criteria (Herzum et al.,
2008).
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Procalcitonin: a marker of bacteraemia in SIRS:
The aim of this study was to assess procalcitonin's performance in an Australian

intensive care unit (ICU) setting to examine whether it could discriminate between sepsis
and SIRS conditions. One hundred and twenty-three consecutive adult ICU patients
fulfilling criteria for SIRS were enlisted in the study. Over a period of five days, daily
serum PCT and C-reactive protein (CRP) levels were measured. At least two sets of
cultures were taken of blood, sputum/broncho-alveolar lavage (BAL) and urine. Other
cultures were taken as clinically indicated. Questionnaires to ascertain clinical suspicion
of sepsis were prospectively answered by the ICU senior registrars. PCT values were ten
times higher in patients with positive blood cultures; CRP values were also significantly
higher in the bacteraemic patients. Both PCT and CRP had a good ability to discriminate
bacteraemia from non-infectious SIRS, with the area under receiver operating
characteristics (ROC) curves for PCT being 0.8 and for CRP being 0.82. However neither
PCT nor CRP was able to discriminate patients with localized sepsis from those without.
Utilizing both tests resulted in a more sensitive screen than either one alone, while PCT
was a more accurate diagnostic test for bacteraemia than CRP. The PCT value also
differed between those who died in hospital and those who survived. Measurement of
PCT alone or in combination with CRP can aid discrimination of septicaemia/bacteriemia
with associated SIRS from non-infectious SIRS in an Australian ICU setting (Bell et al.,
2003).
Procalcitonin and C-reactive protein as markers of systemic inflammatory response

syndrome severity in critically ill children:
The clinical value of procalcitonin (PCT), C-reactive protein (CRP) and leucocyte
count in the diagnosis of pediatric sepsis and in the stratification of patients according to
severity were analyzed. Leucocyte count, PCT and CRP were measured when considered
necessary during the PICU stay. Patients were classified, when PCT and CRP were
measured, into one of six categories (negative, SIRS, localized infection, sepsis, severe
sepsis, and septic shock) according to the definitions of the American College of Chest
Physicians /Society of Critical Care Medicine. A total of 359 patient day episodes were
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obtained. Leucocyte count did not differ across the six diagnostic classes considered.
Median plasma PCT concentrations were 0.17, 0.43, 0.79, 1.80, 15.40 and 19.13 ng/ml in
negative, systemic inflammatory response syndrome (SIRS), localized infection, sepsis,
severe sepsis, and septic shock groups, respectively, whereas median plasma CRP
concentrations were 1.35, 3.80, 6.45, 5.70, 7.60 and 16.2 mg/dl, respectively. The area
under the ROC curve for the diagnosis of septic patients was 0.532 for leucocyte count
(95% CI, 0.462-0.602), 0.750 for CRP (95% CI, 0.699-0.802) and 0.912 for PCT (95%
CI, 0.882-0.943). We obtained four groups using CRP values and five groups using PCT
values that classified a significant percentage of patients according to the severity of the
different SIRS groups. PCT is a better diagnostic marker of sepsis in critically ill children
than CRP. The CRP, and especially PCT, may become a helpful clinical tool to stratify
patients with SIRS according to disease severity (Rey et al., 2007).
Comparison of procalcitonin and C-reactive protein as markers of sepsis:
The clinical informative value of procalcitonin (PCT) and C-reactive protein

(CRP) plasma concentrations in the detection of infection and sepsis and in the
assessment of severity of sepsis were compared. PCT and CRP plasma concentrations
were measured daily during the intensive care unit stay. Each patient was examined daily
for signs and symptoms of infection and was classified daily in one of the following four
categories according to the American College of Chest Physicians/Society of Critical
Care Medicine criteria: negative, systemic inflammatory response syndrome, localized
infection, and sepsis group (sepsis, severe sepsis, or septic shock). The severity of sepsis-
related organ failure was assessed by the sepsis-related organ failure assessment score. A
total of 800 patient days were classified into the four categories. The median plasma PCT
concentrations in noninfected (systemic inflammatory response syndrome) and localized-
infection patient days were 0.4 and 1.4 ng/mL (p <.0001), respectively; the median CRP
plasma concentrations were 79.9 and 85.3 mg/L (p =.08), respectively. The area under the
receiver operating characteristic curve was 0.756 for PCT (95% confidence interval [CI],
0.675-0.836), compared with 0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median
plasma PCT concentrations in nonseptic (systemic inflammatory response syndrome) and
septic (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p
18
<.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001),
respectively. The area under the receiver operating characteristic curve was 0.925 for
PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622-0.733) (p
<.0001). The linear correlation between PCT plasma concentrations and the four
categories was much stronger than in the case of CRP (Spearman's rho, 0.73 vs. 0.41; p
<.05). A rise in sepsis-related organ failure assessment score was related to a higher
median value of PCT but not CRP. PCT is a better marker of sepsis than CRP. The
course of PCT shows a closer correlation than that of CRP with the severity of infection
and organ dysfunction (Luzzani et al., 2003).
Procalcitonin: A valuable indicator of infection in a medical ICU:
The use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU
was assessed. Seventy-seven infected patients and 24 patients with systemic
inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could
be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20
SIRS patients remained free from infection during the study. Plasma PCT and C-reactive
protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4.
As compared with SIRS, PCT and CRP levels at day 0 were higher in infected patients,
regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92
mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l
(CRP), sensitivity and specificity were 65% and 70% (PCT), 74% and 74% (CRP). PCT
and CRP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and
173 +/- 98 mg/l) than in SIRS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7
ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) (all
p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIRS
(p<0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher
PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response
to septic shock. In this study, PCT and CRP had poor sensitivity and specificity for the
diagnosis of infection. PCT did not clearly discriminate SIRS from sepsis or severe sepsis
(Suprin et al., 2000).
19
Toward an operative diagnosis in sepsis: a latent class approach:
Cross-sectional study to determine the operative characteristics of three biological

markers of inflammation and coagulation (D-dimer, C-reactive protein and Procalcitonin)
as diagnostic tests for sepsis, in patients admitted to hospital care with a presumptive
infection as main diagnosis. There are alternative techniques that have been used to
assess the accuracy of tests without gold standards, and they have been widely used in
clinical disciplines such as psychiatry, even though they have not been tested in sepsis
diagnosis. Considering the main importance of diagnosis as early as possible, this article
proposes a latent class analysis to evaluate the accuracy of three biomarkers to diagnose
sepsis (Rosa et al., 2008).
The diagnostic value of procalcitonin in severe sepsis:
Sepsis and its complications are the most common cause of the death in the
intensive care unit. In spite of the treatment mortality remains up to 28-50%, and 60-90%
of the patients are lost because of the complications of sepsis. So it is very important to
diagnose this pathology and start the treatment early. The diagnosis of sepsis is
complicated for clinical signs and symptoms are not specific and manifest in the patients
who have non-infective diseases, when systemic inflammatory response is involved.
Parameters of systemic inflammatory response, such as body temperature, heart rate,
respiratory rate, leukocyte count, and C-reactive protein concentration, used in clinical
practice are neither specific, non sensitive. These parameters often provide information
that is inadequate for the discrimination of bacterial and nonbacterial infections and for
diagnosis. So it is impossible to differentiate systemic inflammatory response and sepsis.
Procalcitonin is a new parameter for diagnosis of bacterial, fungal and parasitical
infections. In healthy humans almost all procalcitonin, which is produced in thyroid
gland, is resolved and does not reach the blood stream. Its half-life in plasma is only few
minutes, so in healthy humans the level of procalcitonin is very low (<0.1 ng/ml) and is
not detectable by standard methods. In the case of infection the level of procalcitonin
rapidly increases during 2-6 hours and reaches the maximum level after 6-12 hours. The
measurement of procalcitonin levels can be used for instant diagnosis as well as for
20
evaluation of the treatment effectiveness. In our article we review the new literature data
on the importance of procalcitonin level for sepsis diagnosis in comparison with other
parameters of systemic inflammatory reaction, and discuss the indications for
procalcitonin analysis (Andrejaitiene, 2006).
Procalcitonin does discriminate between sepsis and systemic inflammatory response

syndrome:
The aim in this work was to evaluate whether procalcitonin (PCT) and C reactive
protein (CRP) were able to discriminate between sepsis and systemic inflammatory
response syndrome (SIRS) in critically ill children. Kinetics of PCT and CRP were
studied in patients undergoing open heart surgery with cardiopulmonary bypass and
patients with confirmed bacterial sepsis. In group I, PCT median concentration was 0.24
ng/ml (reference value <2.0 ng/ml). There was an increment of PCT concentrations
which peaked immediately after CPB (median 0.58 ng/ml), then decreased to 0.47 ng/ml
at 24 h; 0.33 ng/ml at 48 h, and 0.22 ng/ml at 72 h. CRP median concentrations remained
high on POD1 (36.6 mg/l) and POD2 (13.0 mg/l). In group II, PCT concentrations were
high at admission (median 9.15 ng/ml) and subsequently decreased in 11/14 patients who
progressed favourably (median 0.31 ng/ml). CRP levels were high in only 11/14 patients
at admission. CRP remained high in 13/14 patients at 24 h; in 12/14 at 48 h; and in 10/14
patients at 72 h. Median values were 95.0, 50.9, 86.0, and 20.3 mg/l, respectively. The
area under the ROC curve was 0.99 for PCT and 0.54 for CRP. Cut off concentrations to
differentiate SIRS from sepsis were >2 ng/ml for PCT and >79 mg/l for CRP. PCT is able
to differentiate between SIRS and sepsis while CRP is not. Moreover, unlike CRP, PCT
concentrations varied with the evolution of sepsis (Arkader etal., 2006).
Procalcitonin in children admitted to hospital with community acquired

pneumonia:
The sensitivity, specificity, and predictive value of procalcitonin (PCT) in

differentiating bacterial and viral causes of pneumonia was assessed in this article. A total
21
of 72 children with community acquired pneumonia were studied. Ten had positive blood
culture for Streptococcus pneumoniae and 15 had bacterial pneumonia according to
sputum analysis (S pneumoniae in 15, Haemophilus influenzae b in one). Ten patients
had Mycoplasma pneumoniae infection and 37 were infected with viruses, eight of whom
had viral infection plus bacterial coinfection. PCT concentration was compared to C
reactive protein (CRP) concentration and leucocyte count, and, if samples were available,
interleukin 6 (IL-6) concentration. PCT concentration was greater than 2 microg/l in all
10 patients with blood culture positive for S pneumoniae; in eight of these, CRP
concentration was above 60 mg/l. PCT concentration was greater than 1 microg/l in 86%
of patients with bacterial infection (including Mycoplasma and bacterial superinfection of
viral pneumonia). A CRP concentration of 20 mg/l had a similar sensitivity but a much
lower specificity than PCT (40% v 86%) for discriminating between bacterial and viral
causes of pneumonia. PCT concentration was significantly higher in cases of bacterial
pneumonia with positive blood culture whereas CRP concentration was not. Specificity
and sensitivity were lower for leucocyte count and IL-6 concentration. PCT
concentration, with a threshold of 1 microg/l is more sensitive and specific and has
greater positive and negative predictive values than CRP, IL-6, or white blood cell count
for differentiating bacterial and viral causes of community pneumonia in untreated
children admitted to hospital as emergency cases (Moulin et al., 2001).
Usefulness of procalcitonin and some inflammatory parameters in septic patients:
The objective of this study was to evaluate the efficacy of procalcitonin PCT to
identify critically ill patients with sepsis in comparison with leukocyte count, body
temperature, C-reactive protein CRP, erythrocyte sedimentation rate ESR, and
interleukin-6 IL-6. The prospective observational study was performed in 75 patients
admitted with acute systemic inflammatory response and suspected infection. The final
diagnosis was systemic inflammatory response syndrome SIRS in 38 patients, sepsis in
22, severe sepsis in 10, and suspected viral sepsis in 5. Blood samples were taken on the
first day of hospitalization in Al Mwasaa Hospital, Damascus, Syrian Arab Republic,
from July 2006 to January 2007. The relevance of the different parameters by using the t-
test, Pearson's correlation coefficient, and area under the receiver operating characteristic
22
curves were estimated. Mean PCT concentrations on admission were 0.37 ng/ml for SIRS
n=38, 3.31ng/ml for sepsis n=22, 40.2 ng/ml for severe sepsis n=10, and significant
differences existed in plasma PCT levels among the 3 groups. The PCT was the only
distinguisher between sepsis and non-infectious SIRS, whereas it exhibited the best
discriminative power between sepsis and severe sepsis with an area under the curve AUC
of 0.966 followed by IL-6 with an AUC of 0.836. The PCT also do not correlate with any
of the studied parameters within the SIRS group and the sepsis group (Tasabehji et al.,
2008).
Discrimination of sepsis and systemic inflammatory response syndrome by

determination of circulating plasma concentrations of procalcitonin, protein
complement 3a, and interleukin-6:
The aim in this case was to evaluate whether plasma concentrations of

procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte
elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical
onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate
between patients suffering from sepsis or SIRS and predict the outcome of these patients
The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset
of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic
patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807
ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004
pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from
SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range,
279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a,
and IL-6 to discriminate between septic and SIRS patients was determined in a receiver
operating characteristic analysis. C3a was the best variable to differentiate between both
populations with a maximal sensitivity of 86% and a specificity of 80%. An even better
discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved
when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to
predict the outcome of patients. Based on the sepsis score, a logistic regression model
was developed that allows a convenient and reliable determination of the probability of
23
an individual patient to suffer from sepsis or SIRS. The data show that the determination
of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients
than the variables CRP and elastase, routinely used at the intensive care unit. The
determination of PCT and C3a plasma concentrations appears to be helpful for an early
assessment of septic and SIRS patients in intensive care (Selberg et al., 2000).
Plasma procalcitonin in sepsis and organ failure:
Thirty-five patients with non-septic SIRS (n = 16), sepsis (n = 7) or septic shock

(n = 12) were included in this study. PCT and C-reactive protein (CRP) levels were
measured and sepsis-related organ failure assessment (SOFA) score was calculated for
these patients. Plasma PCT was measured by immunoluminometric assay. The median
(minimum, maximum) plasma PCT levels were 0.6 (0.1, 3.4) ng/mL in non-septic SIRS,
5.4 (0.9, 47.7) ng/mL in sepsis and 73.4 (9.6, 824.1) ng/mL in septic shock, and
significant differences existed in plasma PCT levels among the three groups. The median
(minimum, maximum) CRP levels were 13.8 (0.3, 48.8) mg/dL in non-septic SIRS, 23.3
(1.4, 26.6) mg/dL in sepsis and 17.4 (2.2, 34.1) mg/dL in septic shock, without significant
differences among the three groups. A good correlation was found between plasma PCT
level and SOFA score (rs = 0.766, P < 0.0001), although no correlation was found
between CRP level and SOFA score. CRP is increased by inflammatory disease as well
as infection and is therefore not a good indicator of infection in patients with severe
SIRS. On the other hand, PCT is a good indicator of severity of sepsis and organ failure
in patients with severe SIRS since PCT levels correlated with sepsis and SOFA scores
(Yukioka et al., 2001).
Reliability of procalcitonin as a severity marker in critically ill patients with

inflammatory response:
Prospective study was designed to investigate PCT as a diagnostic marker of

infection in critically ill patients with sepsis. Eighty-five adult ICU patients were studied.
Four groups were defined on the basis of clinical, laboratory and bacteriologic findings as
24
systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n = 16), severe sepsis
(n = 18) and septic shock (n = 41). Data were collected including C-reactive protein
(CRP), PCT levels and Sequential Organ Failure Assessment and Acute Physiology and
Chronic Health Evaluation II scores on each ICU day. PCT levels were significantly
higher in patients with severe sepsis and septic shock (19.25 +/- 43.08 and 37.15 +/-
61.39 ng/ml) than patients with SIRS (0.73 +/- 1.37 ng/ml) (P < 0.05 for each
comparison). As compared with SIRS patients, plasma PCT levels were significantly
higher in infected patients (21.9 +/- 47.8 ng/ml), regardless of the degree of sepsis (P <
0.001). PCT showed a higher sensitivity (73% versus 35%) and specificity (83% versus
42%) compared to CRP in identifying infection as a cause of the inflammatory response.
Best cut-off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. It is suggested that
PCT is a more reliable marker than CRP in defining infection as a cause of systemic
inflammatory response (Tugrul et al., 2002).
Procalcitonin and infection in elderly patients:
The usefulness of procalcitonin (PCT) in detecting infection in elderly patients

with that of other clinical and biological markers was compared. Demographic
characteristics, comorbidities, Charlson index, general signs (respiratory rate,
temperature, pulse rate, confusion, falls, shivering), presence of systemic inflammatory
response syndrome (SIRS), sepsis, severe sepsis, septic shock, functional score
(Functional Independence Measurement (FIM)) biological parameters (PCT, C-reactive
protein (CRP), leukocytes, albumin), and definite diagnosis at admission were collected
prospectively for each patient. Long-term corticotherapy, chronic immune diseases, fever
of 38 degrees C or higher, white blood cell count, pulse rate, FIM, SIRS, sepsis, CRP of 3
mg/mL or higher, and PCT of 0.5 ng/mL or higher were associated with an infection at
admission. In multivariate analysis, only sepsis and CRP of 3 mg/mL or higher were still
associated with an infection; PCT levels do not show any significant association in the
multivariate analysis. In addition, when PCT had good specificity (94%), it had low
sensitivity (24%). False-negative PCT was related to lower severity of infection (lower
inflammatory reaction and lower acute renal failure) than true-positive PCT. This finding
may also be related to aging per se. PCT may be useful to identify severely ill elderly
25
patients admitted to an acute geriatric ward but not to discriminate patients with infection
from those without (Stucker et al., 2005).
Plasma procalcitonin and C-reactive protein in acute septic shock: clinical and
biological correlates:
The objective was to determine the relationship between plasma procalcitonin

(PCT) levels, C-reactive protein (CRP), white blood cell count (WBC), ionized calcium
(Ca2+), and patient outcome; and to compare the diagnostic and prognostic information
provided by PCT and by CRP. Blood was sampled at diagnosis and 24 and 48 hrs later
and in a subgroup (n = 23) after 120 hrs. PCT was measured with LUMItest and CRP
with Vitros slides. Ca2+ was calculated according to McLean-Hastings from calcium and
protein levels on Vitros. In all 53 patients, PCT and CRP were elevated (>0.5 ng/mL and
>10 mg/L, respectively) within 24 hrs after diagnosis. Nonsurvivors (n = 25) were older
(p <.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II
scores (p =.02) at diagnosis but did not differ in sepsis etiology, medical history, sex
ratio, levels of PCT, CRP, and Ca2+, or WBC count at any time point. Using logistic
regression, initial PCT levels were correlated with CRP values (p =.001) and APACHE II
score (p <.05), but not with age, gender, Ca2+ levels, survival, or type of pathogen.
Within 48 hrs, however, PCT levels decreased more frequently from baseline in survivors
than in nonsurvivors (80% vs. 41%, p <.05). Likewise, CRP levels decreased more often
in survivors (100% vs. 64%, p <.05) but only at 120 hrs. PCT levels were correlated with
the severity of disease at onset (APACHE II) and inflammation (CRP) but not with Ca2+
levels. Inaugural PCT or CRP levels per se poorly predicted outcome but decreasing
levels were associated with a higher probability of survival. In this respect, PCT was
found to be an earlier marker than CRP (Claeys et al., 2002).
MATERIALS AND METHODS
In this study a total of 173 cases of PCT measurement was considered. Of the
total 173 cases, for 161 of them blood culture work also was done and compared with the
PCT results and the reliability of PCT was estimated. For rest of the 12 cases, treatment
26
was given only based on PCT results and the recovery of patients was observed. In the
161 cases, the patients were classified into three groups based on their age. The groups
were Age group I consisting of patients in the age 0-5 years; Age group II consisting of
patient in the age 5-12 years and Age group III consisting of patient in the age 12-18
years. Patients in all age group obtained PCT value in normal, equivocal and high ranges.
Thus based on the comparison between PCT result and blood culture result, the positive
predictive value percentage on the whole and for each age group was calculated
separately. The methods used for the determination of PCT and the determination of
bacterial infection using blood culture technique are discussed below.
The measurement of PCT with LUMItest PCT, an immunoluminometric assay

(ILMA) is easy and can be completed within 2 hours. In LUMItest PCT, two antigen-
specific monoclonal antibodies that bind procalcitonin (the antigen) at two different
binding sites (the calcitonin and the katacalcin segments) are present in excess. One of
these antibodies is luminescence –labeled (tracer) whereas the other is adhered to the
inner wall of the test tube (coated tube system).
During the course of incubation, both antibodies react with the procalcitonin
molecules in the sample to form so-called “sandwich complexes” whereby the
luminescence labeled antibody is bounded to the surface of the tube. Once the reaction
is completed, the excess tracer is completely removed from the tube with careful rinsing
and discarded.
The amount of residual tracer bound to the test tube wall after rinsing is quantified
by measuring the luminescence signal using a suitable luminometer and the LUMItest
Basiskit reagents. The intensity of the luminescence signal (Relative Light Units, RLU)
is directly proportional to the PCT concentration the sample. After a standard curve has
been established using standards with the known antigen concentrations (calibrated
against recombinant intact human procalcitonin), the unknown PCT concentrations in
patient sera or plasma samples can be quantified by comparison to the standard curve.
Lumat LB9507 was the luminometer used for the measurement of the PCT levels
in blood. This instrument is a semi-automatic, user-friendly luminometer for universal
use in bio- and chemiluminense. IT` s equipped with up to 2 reagent injectors, a highly
sensitive photomultiplier, flexible software and a highly advanced, easy-to-handle
27
mechanical system. Qualitative classification of unknown samples can also be done
using the “cut-off method”
In cut-off measurements, using negative and positive standards, unknown samples
are classified quantitatively by interpreting the results of the measurements on the basis
of predefined RLU limits. In quantitative measurements (LIA, ILMA), known standard
concentrations are measured before the unknown samples. After transformation of the
calibration curve, the program interpolates standards and unknown samples. A specially
developed rotating sample holder and transport system for 2 test tubes allows samples to
be measured and loaded in parallel. This almost doubles the sample throughput during the
normal measurement duration of 5 to 10 seconds, thus equaling the speeds reached by
automatic systems.
The emitted light is measured by a special high-sensitivity, low-noise
photomultiplier. Its spectral sensitivity covers a range between 390 and 620 nm. All
established applications in bio- and chemiluminescence emit in this wavelength range.
The photomultiplier operates as an ultra-fast photon counter. The photoelectrons
released from the photocathode by the light quanta are multiplied via a dynode chain and
trigger a fast pulse with a rise time of a few nanoseconds at the anode. These pulses are
then amplified by a very fast amplifier. A threshold discriminator suppresses the low-
energy pulses caused by the noise of the photomultiplier. The single pulses are counted
digitally, their total number being directly proportional to the emitted quantity of light.
However, the “relative light units” (=RLU) are used as a unit of measurement for
the raw data, and not the number of pulses. The number of RLU s is found by dividing
the directly counted pulses by ten; moreover, the raw data are multiplied by the RLU-
factor which allows compensation of the inevitable individual fluctuations of the cathode
sensitivity of various photomultipliers.
The kinetics of many chemiluminescence reactions is so fast that typical counting
time are in the range of 1-5 s per measurement. Thus, sample throughputs of 600 samples
per hour are possible in this instrument
All kit components were warmed up to room temperature. Tracer was
reconstituted. All liquid reagents (including patient’s sera) were gently agitated before
28
use. Washing solution preparation: 11ml concentrate was diluted with distilled water to
yield 550ml. The luminometer was prepared for use.
Patient’s blood sample was allowed to clot and then centrifuged to obtain the
serum. 20µl of the obtained serum was added in a test tube. 250µl of tracer was pipetted
into test tube. The tube was mixed for a short period of time on a sample mixer to ensure
homogeneity of the liquid. The test tube was covered with adhesive foil and incubated on
a horizontal shaker for 1 hr to 1 hr 15 min at room temperature (the tubes were protected
from light during incubation). 1ml of washing solution was added prior to decanting the
liquid off completely. The washing step alone was repeated 4 times. After the last rinsing
step, the test tube was turned upside down and allowed to drain for 5-10 minutes on a
clean blotting paper. The tube was placed in the luminometer and PCT level in the
sample was measured. The luminescence measurement was started with automatic
injection of 300 µl LUMItest Basiskit reagents 1 and 2. Recommended measuring time is
1 sec per tube. The above given protocol was performed for the 31 cases and the results
were compared with those of blood culture technique.
There were two phases in determining the organism present in blood serum. The
patient’s blood sample was clotted and centrifuged to obtain serum. This was tested for
the presence of pathogenic organisms. The first phase involved the use of culture bottles
available for the general growth of a group of organisms present. Then the second phase
involved inoculation of serum in culture plates. This was to recognize the specific type of
organism.
Bact/Alert PF culture bottles were used with Microbial Detection System (M.D.S)
in qualitative procedures for enhanced recovery and detection of aerobic and facultative
anaerobic micro-organism (bacteria and yeast) from blood. The Bact/Alert M.D.S. was
used to determine if micro-organisms were present in blood taken from a patient
suspected of having a bacterial infection. The culture bottle was placed into the
instrument where it was incubated and continuously monitored for the presence of micro-
organisms that will grow.
M.D.S. uses a calorimetric sensors and reflected light to monitor the presence and
production of CO2 dissolved in culture medium. If micro-organisms are present then the
29
CO2 is produced as they metabolize and the color of gas permeable sensor installed in the
bottom of each bottle changes from blue-green to yellow.
The plastic flip-top was removed from culture and disinfected with an alcohol pad
or equivalent. The sample was transferred into the culture bottle using aseptic technique.
The bottle was placed in the M.D.S. system for detection. The bottles showing growth of
micro-organism were taken and those samples were plated in three different plates for
recognition of specific type of organism.
Three types of plates were put using three different medium and the grown culture
from the bottle was inoculated in all plates using spread plate technique. From the plates
the colonies were identified. The three medium used for plating were chocolate agar,
blood agar and mac conkey agar (M081-500G)
Nutreint agar was prepared as follows. 280g of the agar powder was suspended in
1000 ml distilled water. The mixture was heated to dissolve the contents completely. The
medium was autoclaved at 15 lbs (121ºC) for 15 min. The final pH was brought to 7.4
+or- 0.2 at 25ºC.
For the preparation of chocolate agar, 10% of sheep blood was added to nutrient
agar before heating and autoclaving. Thus chocolate agar was obtained. For the
preparation of blood agar, 10% of sheep blood was added to nutrient agar after
autoclaving and cooling i.e., during plating. Thus blood agar was obtained. For the
preparation of Mackonkey agar, 51.5g of agar powder was suspended in 1000ml of
distilled water. Then it was heated with gentle swirling to dissolve the agar completely.
Autoclaving of the medium was done at 15 lbs (121ºC) for 15 min. Care was taken not to
over heat the medium. The final pH was brought to 7.1 +or- 0.2 at 25ºC. The solution
was cooled to 45 to 50ºC and poured into sterile Petri-plates. The inoculation was done
only when the surface of the medium was dry. All three types of media were used for
plating. The inoculation of samples was done using spread plate technique.
RESULTS
The PCT values were measured using luminometer and thus PCT result of a blood
sample was obtained within 2 hrs of obtaining the sample from the patient. However the
corresponding blood culture results were obtained only after two days from the date of
30
PCT. These were tabulated. The results were classified and tabulated based on the age
group of the patient and the range of PCT. The blood culture results can identify the
specific type of organism or at least if it was gram +ve or –ve organism. In certain case
though the C - reactive protein (CRP) was estimated to confirm infection. The CRP +ve
test denotes the presence of bacteria and vice versa.
The cases with normal PCT values were separately tabulated. They were also
classified into three different age groups. It was observed that patients in the age group 5-
12 and 12-18 with normal PCT show no infection in this study. However 3 patients in the
age group 0-5 with normal PCT had shown +ve blood culture result. The others though
were as expected. These 3 cases were false negatives and depicted in fig.1 and used in the
negative predictive value (table-1 and fig1, 2 and 3).
TABLE 1: NORMAL PCT VALUES AND THE CORRESPONDING CULTURE

RESULT:
S.No. DATE PATIENT’S NAME AGE/ PCT CULTURE DETAILS

SEX VALUE
AGE GROUP – 0-5
Yrs:
1. 2/5/07 Varsini 2y/F 0.37 No growth
2. 2/5/07 Aakash 4y 3m/M 0.39 No growth
3. 9/6/07 Divya 6m/F 0.10 Enterocens sp
4. 15/6/07 Sai Ganesh.S 2y 6m/M 0.20 No growth
5. 9/7/07 Pooja 3y/F 0.4 Kleb. Pneumoniae +
P.aeruginosa
6. 9/7/07 Swetha 3y 6m/F 0.2 No growth
7. 25/10/07 Abdul Rahman 1y/m 0.29 No growth
8. 3/11/07 Gayathri.S 1y 6m/F 0.45 No growth
9. 5/11/07 Abdul Rahman 1y/M 0.36 No growth
10. 19/11/07 B/o Geetha 44d/F 0.20 No growth
11. 23/11/07 B/o Prathibha 3m/M 0.33 No growth
12. 14/12/07 Samrudh.S 1.5y/M 0.32 No growth
13. 19/12/07 Rohit 3y 6m/M 0.44 No growth
14. 26/12/07 C.Aarthi 28d/F 0.38 No growth
15. 29/12/07 Sugandan 2y 6m/M 0.49 No growth
16. 4/1/08 HarshaVardan 1y/M 0.29 No growth
17. 8/1/08 Yogesh 1m/M 0.21 No growth
18. 9/1/08 Abriel Paul Rodrigo 3y/M 0.18 No growth
19. 21/1/08 Pranav 6m/M 0.32 No growth
Subramaniam
31
20. 12/2/08 Kishore.E 3m/M 0.50 No growth
21. 22/2/08 B/o Nirmala 30d/M 0.20 CRP+ve
22. 22/2/08 B/o Sudha 1-2h/F 0.19 CRP-ve
AGE GROUP- 5-12
Yrs:
1. 18/6/07 Gokula Krishnan 6y/M 0.20 No growth

2. 22/11/07 Mir .Mhd .Ali 12y/M 0.17 No growth
3. 10/12/07 Varun Vijay 6y 6m/M 0.45 No growth
4. 22/12/07 Uma Maheshwari 5y 4m/F 0.22 No growth
5. 30/12/07 Marvin Alla .M 6y/M 0.48 No growth
6. 7/1/08 Naasif.M 5y 0.30 No growth
3m/M
AGE GROUP- 12-
18 Yrs:
1. 29/12/07 Manodhini 13y/F 0.22 No growth
The PCT values obtained, that were in equivocal condition were tabulated in a
manner similar to that of normal conditions. Patients in this category were also classified
based on their age. Equivocal condition neither confirms infection nor denies it. Here also
the culture results show growth in some cases and no growth in the others. 31 cases of no
growth and 20 cases of growth were obtained for this condition. Infections due to candida
species were also observed. Follow Up Repeats (re-tests) were done after a few days to
confirm infection. Some times follow up repeats were done even during the prognosis
period of the disease. This was done to check if the infection were under control of if the
treatment given was effective (table-2 and fig1, 2 and 3).
TABLE 2: EQUIVOCAL PCT VALUES AND THEIR BLOOD CULTURE RESULT:
S.No. DATE PATIENT’S AGE/ PCT CULTURE DETAILS

NAME SEX VALUE
AGE GROUP- 0-5
32
Yrs:
1. 8/5/07 Aroul Aakash 1y/M 1.89 GPC in clusters(staph)

2. 11/5/07 Karthick 4y/M 1.42 No growth
3. 12/5/07 Logeswari 10m/F 1.83 CONS + aerobics(GPC)
4. 14/5/07 B/o Beatrice 2y/F 1.60 E.coli (104 -105
CFU/ml)ESBL producing
strain
5. 14/5/07 Aroul Aakash 1y/M 1.42 FUT
6. 22/5/07 Sadhfa.K 3y 6m/F 1.47 PC seen/ no org
7. 30/6/07 B/o Sunitha 2m/M 1.09 No growth
8. 9/7/07 B/o Vennila 45d/M 1.8 103 – 104 CFU/ml candida
non-albicans sp
9. 19/7/07 Uma Maheswari 4d/F 1.06 No work done
10. 23/7/07 B/o Rekha 1y 6m/F 1.46 No growth
11. 27/7/07 B/o Rekha 1y/F 1.05 FUR
12. 27/7/07 Raunak agarwal 9m/M 0.55 No growth
13. 6/8/07 Pushpa.R 4y/F 1.42 Enterococus sp(105) + P.
aeruginosa(103 – 104)
14. 20/8/07 Mahathi.V 4y 6m/F 1.9 No work done
15. 24/9/07 NitinKumar 7m/M 1.54 No growth
16. 27/9/07 Rupesh.B.M 2y/M 1.84 FUR
17. 28/9/07 Raihana Thazneem 2y 6m/F 1.51 No growth
18. 12/10/07 Akshaya.K 4m/F 1.65 Kleb. Pnemoniae
19. 15/10/07 Dresh.R 4m/M 1.14 No growth
20. 22/10/07 Oviya.S 7m/F 1.46 No growth
21. 23/10/08 Rahul 7m/M 1.44 No growth
22. 24/10/07 Anshuman Vetrivel 1y/M 0.73 No growth
23. 13/11/07 Carol 1y/F 0.80 No growth
24. 24/11/07 Badthrinathan.M 2y/M 0.60 No growth
25. 28/11/07 Darshera 4y/M 0.74 CRP +ve
26. 24/12/07 Suraj.S 1y/M 0.59 No growth
27. 24/12/07 Sidarth 40d/M 0.83 No growth
28. 26/12/07 Sugandam 1y/M 1.04 No growth
29. 26/12/07 Abriel Paul 3y/M 1.86 FUR
Rodrigo
30. 23/1/08 Harshini 3y/F 1.99 No growth
31. 28/1/08 Ragavendra 1y 0.97 No growth
10m/M
32. 4/2/08 Pranav 6m/M 1.31 No growth
33. 9/2/08 B/o Lakshmi 4m/M 1.08 FUR
34. 16/2/08 Vishali.V 7m/F 0.92 No growth
35. 22/2/08 B/o Syed rabbami 1-2hr/F 0.76 CRP-ve
AGE GROUP- 5-
12 Yrs:
33
1. 2/6/07 Nandhini 9y/F 0.71 No growth
2. 11/6/07 Gokula Krishnan 6y/M 0.78 No growth
3. 3/8/07 Karthick.K 12y/M 1.67 FUR
4. 6/8/07 Senthil 10y/M 1.52 FUR
Aarumugam
5. 29/8/07 Madhan Kumar 12y/M 1.0 FUR
6. 30/8/07 Suraj 8- 1.7 Staphylococcus sp
12y/M
7. 2/10/07 Kalaivani 10y/F 1.28 No growth
8. 3/10/07 Kalaivani 10y/F 1.45 FUR
9. 10/10/07 Prashant.Y 12y/M 0.55 No growth
10. 25/10/07 Sai Gayathri 8y/F 1.81 FUR
11. 1/11/07 Vishnu Kumar.s 11y/M 1.08 No growth
12. 29/11/07 Mir Mhd Ali 12y/M 0.54 P. aeruginosa(>105)
13. 30/11/07 Harish.V 9y/M 0.93 No growth
14. 26/12/07 Manodhini 13y/F 1.0 No growth
15. 26/12/07 Krishna.R 6y/M 1.25 No growth
AGE GROUP- 12-
18 Yrs:
1. 28/9/07 Vignesh.M 14y/M 1.08 No growth

2. 12/12/07 Karakuti 15y/M 1.59 No growth
Venkateshwaralu
3. 26/12/07 Pooja Mishra 14y/F 0.62 No growth
High PCT values were also separately tabulated with age group classification.
Very high PCT values were due to intense infections and in some cases even due to
mixed cultures. There were 24 cases of no growth in the high PCT conditions. These
were false positives and were depicted in fig.3 and included during negatives predictive
value calculation. 57 cases of blood culture positive result were obtained for high PCT.
Here also in some cases CRP was estimated to confirm the infection (table 3 and fig 1, 2
and 3).
TABLE 3: HIGH PCT VALUES AND THE CULTURE RESULT:
S.No. DATE PATIENT’S AGE/ PCT CULTURE DETAILS

NAME SEX VALUE
AGE GROUP- 0-5
34
Yrs:
1. 10/5/07 Kaviya.s 4y/F 21.00 No growth

2. 10/5/07 Ragavendra 8m/M 4.20 No work done
3. 21/5/07 Deepak.P 11m/M 2.03 No work done
4. 28/5/07 Aravind.R 5y/M 2.3 GPC seen
5. 18/6/07 Vishnu.R 6m/M 21.21 No growth
6. 26/6/07 Vishnu.R 6m/M 2.61 FUR
7. 30/6/07 Rajesh.T 1y/M 16.00 PC seen; Candida non-
albicans
8. 2/7/07 Keerthana 3y/F 85.58 No growth
9. 2/7/07 Kalphine 11m/M 2.4 No work done
10. 2/7/07 Shanmatha 1y 6m/F 7.64 No work done
11. 3/7/07 B/o Vennila 47d/M 2.05 No growth
12. 3/7/07 Rajesh.T 1y 5.80 FUR
6m/M
13. 10/7/07 Vishnu.R 6m/M 21.70 B. cepacia + P.
aeruginosa
14. 13/7/07 Fatin 1m/M 2.15 No work done
15. 30/7/07 Kiruthika 11m/F 320 Febrile seizure/ septic
shock
16. 6/8/07 Parthasarathy 3y/M 6.0 No growth
17. 24/8/07 Benjamine Celeb 5y/M 3.66 No growth
18. 27/8/07 Sharath 5y/M 18 No work done
19. 7/9/07 Kelvin Marshal 1y 2.1 No growth
6m/M
20. 14/9/07 Dharshan.KS 5y/M 2.4 Candida tropicalis
21. 17/9/07 Reshma 7m/F 4.38 Kleb. pneumoniae (103 –
104 CFU/ ml)
22. 21/9/07 Rupesh.B.M 2y/M 92.37 GNB seen
23. 12/10/07 Prakash.M 1y/M 3.93 No growth
24. 22/10/07 Akshay Kumar 8m/M 4.68 No growth
25. 13/11/07 S. Aparna 64d/F 69.41 GPC in clusters
26. 24/11/07 Vignesh 4y 26 No growth
Saravanan 6m/M
27. 10/12/07 Samaiya 9m/F 3.79 No work done
28. 18/12/07 Abriel Paul 3y/M 10.22 Acinetobacter sp.
Rodrigo
29. 19/12/07 Abriel Paul 3y/M 5.66 FUR
Rodrigo
30. 20/12/07 Harsha Vardan 2y 94.97 No growth
9m/M
31. 22/12/07 Yuvam Selva 37d/M 13.23 No growth
32. 17/1/08 Varshini 4m/F 101 GPC + Candida sp.
33. 21/1/08 Varshini 4m/F 2.44 FUR
34. 22/1/08 B/o Banulatha 2m/F 2.19 CRP +ve
35
35. 25/1/08 Ashritha 1y 9m/F 48.70 CRP +ve
36. 7/2/08 B/o Lakshmi 4m/M 9.22 GPC in clusters
37. 16/2/08 Saswat Kumar 1y6m/M 4.25 No growth
38. 16/2/08 Kishore.E 3m/M 39.24 FUR
39. 19/2/08 Teja.N 4y/M 25.17 Kleb. pneumoniae
40. 21/2/08 Saswat kumar 1.5y/M 23.20 CRP+ve
41. 22/2/08 Niyati sriram 1.5y/F 4.01 PC seen + GPC in pairs
42. 22/2/08 Vishali.G 7m/F 7.37 No growth
AGE GROUP- 5-
12 Yrs:
1. 10/5/07 Raj Mohan.V 12y/M 11.16 Candida sp +

pseudohyphae seen
2. 10/5/07 Nishanth.S 5-6y/M 2.77 CONS
3. 14/5/07 Rajmohan 12y/M 2.42 FUR
4. 14/5/07 Sukumar 6y/M 2.39 No growth
5. 2/7/07 Manoj Kumar 10y/M 129.99 Entero bacter sp
6. 7/7/07 Archana.S 6y/F 11.89 Kleb. Pneumoniae +
P.aeruginosa
7. 7/7/07 Rohan Prasad 7y/M 2.64 No growth
8. 14/7/07 Senthil 10y/M 7.01 No growth
Aarumugam
9. 17/7/07 Senthil 10y/M 10.69 FUR
Aarumugam
10. 18/7/07 Aradhikaluha 11y/M 2.53 No work done
11. 20/7/07 Karthick.K 12y/M 153.59 No work done
12. 26/7/07 Karthick.K 12y/M 34.42 FUR
13. 26/7/08 Karthick.K 12y/M 7.0 FUR
14. 26/7/07 Anbarasan 12y/M 30.11 CRP+ve
15. 30/7/07 Karthick.k 12y/M 2.85 FUR
16. 14/8/07 Jaya Shanti 8y/F 4.0 No work done
17. 21/8/07 Madhan Kumar 12y/M 3.22 Few PUS cells + GPC
18. 24/8/07 Sandeep.CH 11y/M 3.03 No growth
19. 14/9/07 Dilip.R 8y/M 18 No growth
20. 21/9/07 Dilip.R 8y/M 28.3 FUR
21. 2/10/07 Suprajaa 10y/F 2.7 No growth
22. 8/10/07 Mahith 12y/M 7.58 CRP +ve
23. 11/10/07 Mahith 12y/M 3.69 FUR
24. 16/10/07 Sai Gayathri 8y/F 93.74 CONS
27. 24/10/07 Arun Srikanth 12y/M 7.21 No growth
28. 2/11/07 Arun Srikanth 12y/M 5.76 FUR
29. 5/11/07 Vishnu Kumar.S 11y/M 55.29 Kleb. pneumoniae (103 –
104 CFU/ ml)
36
30. 7/11/07 Vishnu Kumar.S 11y/M 7.77 FUR
31. 4/12/07 Harish.V 9y/M 2.05 FUR
32. 21/12/07 Dharshini 9y/M 20 No growth
33. 26/12/07 JaiRam.J 7y/M 2.99 CRP +ve
34. 17/1/08 Rasarin.S 10y/F 26 CRP +ve
35. 25/1/08 Ashwin Bala.V 7y 196 CRP +ve
6m/M
36. 28/1/08 Ashwin Bala.V 7y 63.19 FUR
6m/M
37. 1/2/08 Sneha .A 6y/F 3.27 GNB seen
38. 1/2/08 Ashwin Bala .V 7.5y /M 16.12 FUR
39. 4/2/08 Ashwin Bala .V 7y 84.87 FUR
6m/M
40. 5/2/08 Sneha. A 7y/F 2.22 FUR
AGE GROUP 12-
18 Yrs:
1. 17/4/07 Veena 12.5y/F 2.60 GNB; Acinete bacter

species
2. 13/8/07 Prabakaran 13y/M 149.65 Kleb. pneumoniae
3. 17/8/07 Prabakaran 13y/M 42.2 FUR
4. 8/9/07 Sindhuja.K 18y/F 145 No growth
5. 6/11/07 Arun Srikanth 14y/M 231.00 FUR
6. 18/12/07 Praveen 13y/M 3.43 GPC seen
7. 8/1/08 Manodhini 13y/F 27.10 E.coli(ESBL) +
GNB(>105 CFU /ml)
8. 14/2/08 Mhd. Tanveer 14y/M 327 No growth
Ahmed
9. 20/2/08 Mhd. Tanveer 14y/M 28 FUR
Ahmed
ACRONYMS USED IN THE ABOVE GIVEN TABLES:
• FUR- Follow Up Repeat
• GPC- Gram Positive Coli
• GNB- Gram Negative Bacillus
• CFU- Colony Forming Unit
• ESBL- Extended Spectrum Beta - Lactamases
• CRP- C-Reactive Protein
• PC- Pus Cells
• CoNS- Coagulase Negative Staphylococus Species
Considering all patients the predictive values were calculated and tabulated. The
positive predictive value is 51.56% [16.15+35.41]. The Negative predictive value is
16.77% [1.86+14.91]. The Equivocal value obtained is 31.67% [12.42+19.25] (table 4
and fig 3).
37
TABLE 4- POSITIVE, NEGATIVE PREDICTIVE VALUES AND EQUIVOCAL VALUES OF
ALL PATIENTS:
NO. BLOOD PCT NO OF CASES PREDICTIVE

CULURE (out of 161 VALUES
cases) (percent)
I No growth PCT<0.5 26 16.15
II Growth PCT<0.5 3(False 1.86

negative)
III No growth PCT 0.5-2.0 31 19.25
IV Growth PCT 0.5-2.0 20 12.42
V No growth PCT>2.0 24(False 14.91

positive)
VI Growth PCT>2.0 57 35.41
Here patients in the age group of 0-5 were considered and the following values
were obtained. The Positive predictive value obtained is 44.45% [21.11+23.34]. The
Negative predictive value obtained is 18.89% [3.33+15.56]. The Equivocal value
obtained is 36.66% [22.22+14.44] (table 5 and fig.2).
TABLE 5: PREDICTIVE VALUES FOR PATIENT SIN THE AGE GROUP 0-5:
38
CULURE (out of 90 VALUE
cases) (percent)
II Growth PCT<0.5 3(False 3.33

negative)
IV Growth PCT 0.5-2.0 13 14.44

positive)
The patients in age group 5-12 were considered and the predictive values were
obtained. The Positive predictive value obtained is 60.34% [10.34+50.00]. The Negative
predictive value obtained is 13.79% [13.79+0]. The Equivocal value obtained is 25.85%
[13.79+12.08] (table 6 and fig.2).
39
TABLE 6: PREDICTIVE VALUES OF PATIENTS IN THE AGE GROUP 5-12:
casses) (percent)
II Growth PCT<0.5 - -
IV Growth PCT 0.5-2.0 7 12.08

positive)
Patients in the age group 12-18 were analyzed and the following predictive values
were otained. The Positive predictive value obtained is 61.54% [53.85+7.69]. The
Negative predictive value obtained is 15.38% [15.38+0]. The Equivocal value obtained is
23.08% [23.08+0] (table 7 and fig.2).
TABLE 7: PREDICTIVE VALUES OF PATIENTS IN THE AGE GROUP 12-18:
40
cases) (percent)
II Growth PCT<0.5 - -
IV Growth PCT 0.5-2.0 - -

positive)
41
FIG 1: PCT LEVELS IN BLOOD OF PATIENTS WITH RESPECT TO THEIR AGE
GROUP
45
No of patients
40
35
30
25 0-5yr
20 5-12yr
15 12-18yr
10
5
0
<0.5ng/ml 0.5-2ng/ml >2ng/ml
PCT values 
FIG 2: PCT LEVELS IN BLOOD OF PATIENTS AND THEIR PATHOGENIC

BACTERIAL CULTURE RESULTS
50
45
40
35
30
No growth
25
FUT
20
No of patients
Positive
15
10
5
0
<0.5ng/ml 05.-2ng/ml >2ng/ml
PCT values 
42
FIG 3: THE TOTAL NO. OF FALSE POSITIVES, FALSE NEGATIVES AND
EXPECTED RESULTS
90
80
70
60
50
40 NO OF CASES
30
20
10
0
F.N F.P EQUI E.R
ACRONYMS:
F.N- False Negatives
F.P- False Positives
EQUI- Equivocal cases
E.R- Expected Results
43
OTHER OBSERVATIONS
S.No. PCT DONE DEATH ON NAME PCT VALUE

ON
1. 16/4/07 16/4/07 Veena(trial) 2.6
2. 22/5/07 30/7/07 Sadfa. K 1.47
3. 15/6/07 15/6/07 Sai Ganesh 0.20
4. 9/7/07 14/7/07 Pooja.S 0.4
5. 8/9/07 25/9/07 Sindhuja. K 145
6. 14/9/07 25/10/07 Dharshan 2.4
7. 24/10/07 9/12/07 Anshuman 0.73
Vetrivel
8. 6/11/07 7/11/07 Arun Srikanth 231
INFERENCES FROM DEATH

Deaths were rare and few. In most of the cases the date on which PCT was far
from the date of death. So the cause of death may have been different like post surgical
complications and so on. However in 2 important cases, a very high value of PCT was
characterized few days before death. So patients with high value of PCT are in danger
line and must be treated accordingly. The correct antibiotic must be given and PCT value
must be brought down to normal for effective recovery of the patient.
CASES FOR WHICH PCT ALONE WAS DONE

There were totally 12 cases for which blood culture was not done and treatment
was given on the basis of PCT test alone. Ten of those cases were in the high range; and
by administration of appropriate antibiotic the level of PCT was brought down and the
patients were cured. Two of the equivocal cases were advised for re-testing.
DISCUSSION
44
Many works were done on procalcitonin and its usefulness in the early detection
of bacterial sepsis. And reasonable results were obtained for those experiments. This
study and its results can be discussed with by making a comparison with other similar
experiments. More experiments were done by comparing CRP with PCT. However, here
PCT was compared with blood culture results.
In the work done by Schroder et al , to evaluate the prognostic value in septic
shock PCT levels were repeatedly determined and compared with TNF-α, IL-6 and CRP
serum levels. In this study however, the prognosis was determined by considering PCT
values alone which decrease by 50% as the infection is brought under control. Schroder
determined TNF-α, IL-6, CRP and PCT levels on days 1,3,5,7,10and 14 following
diagnosis of septic shock. But here PCT was determined on the same day as blood culture
test was done. It was for diagnosis of disease (Schroder et.al., 1999).
Cardelli et al., worked on the evaluation of neutrophil CD64 expression.
Quantitation of neutrophil CD64 expression and PCT levels in blood samples was
proposed as tools for early detection of sepsis. The neutrophil CD64 test showed higher
specificity in detecting sepsis and hence could be taken into consideration as a sensitive
and specific test for early detection of sepsis. Here though PCT test was considered to be
more specific, blood culture test gave a clearer picture as the type of organism can also be
determined. Yet being quicker PCT was preferred mainly in ICU patients (Cardelli.
et.al., 2008).
The diagnostic usefulness of PCT, CRP and immature to total neutrophil ratio in
nosocomial sepsis among neonates was studied by Fendler et al., in 2008. PCT was
significantly better in diagnosis of sepsis that CRP-neutrophil ratio which confirms this
study’s result as of PCT being better. In the current study however PCT was compared
and found better against blood culture test rather than CRP-neutrophil ratio. Fendler
found that the positive and negative predictive values of PCT in the diagnosis of sepsis
equaled 97.5% and 88.9% but this study the values were considerably less, as less
number of patients were taken into account. Also this study was on under-18 children on
the whole whereas Fendler’s was on preterm neonates.
45
The role of procalcitonin in the early detection of sepsis in an Australian intensive
care-high dependency unit (ICU/HDU) was evaluated by Muthaiah et al. Serum PCT
levels and the vital signs required to score the criteria for systemic inflammatory response
syndrome (SIRS) and sepsis were recorded daily until the patient left the ICU. Still in this
case only PCT was measured but in we calculated PCT and also did blood culture test.
This study independently confirms the obtained result that PCT is used for the diagnosis
sepsis and SIRS (Muthiah et al., 2007).
Furthermore, in the work done by Bell et al., the use of PCT test to differentiate
sepsis and SIRS was done in Australian intensive care units. One hundred and twenty-
three consecutive adult ICU patients fulfilling criteria for SIRS were enlisted in the study.
Over a period of five days, daily serum PCT and C-reactive protein (CRP) levels were
measured. The study however was based on adult patients. The current one though was
only done with children blood sample (Bell et al., 2003).
The clinical value of procalcitonin (PCT), C-reactive protein (CRP) and leucocyte
count in the diagnosis of pediatric sepsis and in the stratification of patients according to
severity were analyzed by Rey et al. Leucocyte count, PCT and CRP were measured
when considered necessary during the PICU stay. Median plasma PCT concentrations
were 0.17, 0.43, 0.79, 1.80, 15.40 and 19.13 ng/ml in negative, systemic inflammatory
response syndrome (SIRS), localized infection, sepsis, severe sepsis, and septic shock
groups, respectively, whereas median plasma CRP concentrations were 1.35, 3.80, 6.45,
5.70, 7.60 and 16.2 mg/dl, respectively. PCT is a better diagnostic marker of sepsis in
critically ill children than CRP. Current study though compares blood culture test with
PCT and PCT is more effective than culture results (Rey et al., 2007).
Luzzani et al., did their study similar to Rey’s. They also compared CRP with
PCT. Their result was as follows. PCT is a better marker of sepsis than CRP. The course
of PCT shows a closer correlation than that of CRP with the severity of infection and
organ dysfunction.
46
SUMMARY
Procalcitonin(PCT) is known to be secreted not only by the C-cells of thyroid
glands, but also by non-thyroidal tissues when there is extensive bacterial infection. Our
study of 173 cases throws light on the extent of use of PCT levels in predicting bacterial
infection early, to implement early treatment in intensive care children. In the present
study, PCT value was compared with the classical blood culture technique for 161 cases.
The net positive predictive value obtained was 51.56%. In the age group of 5-12, the
positive predictive value obtained was in the 60.34%. The equivocal cases are more
where re-testing needs to be done. PCT is a very sensitive test and it must be noted that
the PCT value will be elevated till the inflammation triggered by bacteraemia comes
under control. The patients whose PCT were tested in the present study were ICU
patients and they were already having antibiotic content in their body which had masked
the presence of bacteria in blood culture technique. So treatment was given with more
weight-age for PCT rather than blood culture. Recovery was also observed as per the
treatment given. By considering the equivocal cases to be positive, a higher positive
predictive value was obtained and the specificity of the test increased. For a very few
cases there were false negatives which depicts that though the organism might be present,
the inflammation triggered by them was brought under control. Hence the value was
slightly negative. PCT value was a better indicator for the amount of bacterial infection
and thus it could be used for diagnosis as well as prognosis of the disease.
47
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plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6;
Crit. Care Med.; 28:2793-8.
16. Stucker F, Herrmann F, Graf JD, Michel JP, Krause KH, Gavazzi G; 2005;
Procalcitonin and infection in elderly patients; J. Am. Geriatr. Soc.; 53:1392-5.
17. Suprin.E, Camus.C, Gacouin.A, Le Tulzo.Y, Lavoe.S, Feuillu.A and Thomas.R;
2000; Procalcitonin: A valuable indicator of infection in a medical ICU?; Intensive
Care Med.; 26:1232-8.
18. Tasabehji WR, Al-Quobaili FA, Al-Daher NA; 2008; Usefulness of procalcitonin and
some inflammatory parameters in septic patients; Saudi Med. J.; 29:520-5.
19. Tugrul S, Esen F, Celebi S, Ozcan PE, Akinci O, Cakar N, Telci L; 2002; Reliability
of procalcitonin as a severity marker in critically ill patients with inflammatory
response; Anaesth. Intensive Care; 30:747-54.
20. Yukioka H, Yoshida G, Kurita S, Kato N; 2001; Plasma procalcitonin in sepsis and
organ failure; Ann. Acad. Med.; 30:528-31.
49
APPENDIX
CULTURE BOTTLES:
COMPOSITION:
• 16 ml of complex media.
• 4 ml of 8.5% charcoal suspention.
MEDIA COMPONENTS:
• Soy bean-casein digest(2.0 %W/V)
• Brain heart infusion solids(0.1 %W/V)
• Sodium poly anetholesulfonate(0.025 %W/V)
• Pyridoxine HCl(0.001 %W/V)
• Menadione(0.0000625 %W/V)
• Hemin(0.000625 %W/V)
• L-Cystein(0.025 %W/V)
• + Other amino acids and carbohydrate substrates in purified water.
COMPOSITION OF NUTRIENT AGAR:
• Peptic digest of animal tissue(5 g/l)

• Beef extract(1.5 g/l)
• Yeast extract(1.5 g/l)
• Nall extract(5 g/l)
• Agar(15 g/l)
COMPOSITION OF MAC CONKEY AGAR:
• Peptic digest of animal tissue(1.5 g/l)

• Casein enzymic hydrolysate(1.5 g/l)
• Pancreatic digest of gelatin(17 g/l)
• Lactose(10 g/l)
50
• Bile salts(1.5 g/l)
• NaCl(5 g/l)
• Crystal violet(0.001 g/l)
• Neutral red(0.03 g/l)
• Agar(15 g/l)
PICTURES:
FIG:1-AMINO ACID SEQUENCE OF PROCALCITONIN.
51
FIG:2-REACTION TAKING PLACE IN THE TEST TUBE.
FIG:3-LUMINOMETER USED FOR MEASUREMENT OF PCT
52

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PROCALCITONIN: AN EARLY MARKER FOR

BACTERIAL SEPSIS-A STUDY OF 173

Sepsis, the systemic inflammatory response to infection, is considered the major

PCT AND SEPSIS

Because of these pathophysiological properties, PCT can be used for the

LEVEL OF PCT IN BLOOD

Normal level of PCT is <0.5ng/ml. It can increase up to 1000ng/ml.It increases in

NEED FOR PCT

THE EFFECT OF PCT ON CALCIUM AND PHOSPHATE CONCENTRATIONS

SYNTHESIS OF PCT AND CALCITONIN

The signal or leader sequence is a markedly hydrophobic sequence and mediates

THE GENE FAMILY OF CALCITONINS

At present, four genes with nucleotide sequence homologies corresponding to

PCT IN THE DIFFERENTIAL DIAGNOSIS OF VIRAL AND BACTERIAL

THE DIFFENTIAL DIAGNOSIS OF VIRAL AND BACTERIAL MENINGITIS

Markedly increased plasma PCT concentrations were detected in children

HIV INFECTION (AIDS)

THE PROGNOSTIC VALUE OF PCT

PCT FOLLOWING REMOVAL OF FOCUS

CLINICAL COURSE ASSESSMENT VIA PCT LEVELS

SPECIAL FEATURES DURING AN ACUTE CLINICAL COURSE

SPECIAL FEATURES OF A PROLONGED CLINICAL COURSE

In some patients, a prolonged clinical course is characterized by low, albeit

Procalcitonin as a marker of severity in septic shock:

Pre-emptive antibiotic treatment vs ‘standard’ treatment in patients with elevated

Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in

Quantitation of neutrophil CD64 expression and procalcitonin (PCT) levels in

Procalcitonin in the early diagnosis of nosocomial sepsis in preterm neonates:

Prospective evaluation of procalcitonin in sepsis in the Illawarra area of Australia:

Procalcitonin (PCT) is a precursor of the hormone calcitonin and has been

Inflammatory Markers in SIRS, Sepsis and Septic Shock:

Despite great advancement in the understanding of the pathophysiology and in the

The aim of this study was to assess procalcitonin's performance in an Australian

Procalcitonin and C-reactive protein as markers of systemic inflammatory response

Comparison of procalcitonin and C-reactive protein as markers of sepsis:

The clinical informative value of procalcitonin (PCT) and C-reactive protein

Procalcitonin: A valuable indicator of infection in a medical ICU:

Cross-sectional study to determine the operative characteristics of three biological

The diagnostic value of procalcitonin in severe sepsis:

Procalcitonin does discriminate between sepsis and systemic inflammatory response

Procalcitonin in children admitted to hospital with community acquired

The sensitivity, specificity, and predictive value of procalcitonin (PCT) in

Usefulness of procalcitonin and some inflammatory parameters in septic patients:

Discrimination of sepsis and systemic inflammatory response syndrome by

The aim in this case was to evaluate whether plasma concentrations of

Plasma procalcitonin in sepsis and organ failure:

Thirty-five patients with non-septic SIRS (n = 16), sepsis (n = 7) or septic shock

Reliability of procalcitonin as a severity marker in critically ill patients with

Prospective study was designed to investigate PCT as a diagnostic marker of

Procalcitonin and infection in elderly patients:

The usefulness of procalcitonin (PCT) in detecting infection in elderly patients

The objective was to determine the relationship between plasma procalcitonin

MATERIALS AND METHODS

The measurement of PCT with LUMItest PCT, an immunoluminometric assay

TABLE 1: NORMAL PCT VALUES AND THE CORRESPONDING CULTURE

S.No. DATE PATIENT’S NAME AGE/ PCT CULTURE DETAILS

1. 18/6/07 Gokula Krishnan 6y/M 0.20 No growth

1. 29/12/07 Manodhini 13y/F 0.22 No growth

TABLE 2: EQUIVOCAL PCT VALUES AND THEIR BLOOD CULTURE RESULT:

S.No. DATE PATIENT’S AGE/ PCT CULTURE DETAILS

1. 8/5/07 Aroul Aakash 1y/M 1.89 GPC in clusters(staph)

1. 28/9/07 Vignesh.M 14y/M 1.08 No growth

TABLE 3: HIGH PCT VALUES AND THE CULTURE RESULT: