Open Journal of Respiratory Diseases, 2013, 3, 73-78
http://dx.doi.org/10.4236/ojrd.2013.32012 Published Online May 2013 (http://www.scirp.org/journal/ojrd)
The Diagnostic and Prognostic Value of
Serum Procalcitonin among Ventilator
Associated Pneumonia Patients*
Ashraf Abd El Halim1, Adel Attia1#, Taysser Zytoun2, Hosam Eldeen Salah3
1Chest Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2Critical Care Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
Received April 2, 2013; revised May 3, 2013; accepted May 10, 2013
Copyright © 2013 Ashraf Abd El Halim et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ventilator-associated pneumonia (VAP) is a complication in as many as 28% of patients who receive mechanical venti-
lation. Studies have consistently shown that a delay in diagnosis and treatment increases the mortality risk. The aim of
this work was to clarify the role of the serum procalcitonin (PCT) in the diagnosis and the prognosis of ventilator asso-
ciated pneumonia. Methods: Forty two VAP patients, 20 non VAP-ICU (on mechanical ventilation) admitted patients
and 20 healthy control subjects of similar age and sex were included in the study. PCT levels in serum samples were
measured in all subjects. Results: There was a highly statistically significant difference (p value < 0.001) between VAP
patients on one side and non VAP-ICU patients and healthy control subjects on the other side regarding the mean values
of PCT. Also, the mean values of PCT were statistically significantly higher (p < 0.001) among died VAP group than
the survivor VAP group. There was a statistically positive correlation (p < 0.01) between mortality prediction scores
(APACHE II (R = 0.449), CRIP (R = 0.403) and SOFA (R = 0.437)) and initial PCT serum levels. Conclusions: This
study found that the increased PCT serum level is an important diagnostic tool for VAP and the PCT serum levels can
predict the outcome of VAP patients. We recommend other larger studies to augment our findings.
Keywords: Ventilator-Associated Pneumonia (VAP); Procalcitonin (PCT); Acute Physiology and Chronic Health
Evaluation II (APACHE II); The Sequential Organ Failure Assessment Score (SOFA); Clinical Pulmonary
Infection Score (CPIS)
Ventilator-associated pneumonia (VAP) is pneumonia
that develops 48 hours or longer after mechanical venti-
lation is given by means of an endotracheal tube or tra-
cheostomy. Ventilator-associated pneumonia (VAP) re-
sults from the invasion of the lower respiratory tract and
lung parenchyma by microorganisms. Intubation com-
promises the integrity of the oropharynx and trachea and
allows oral and gastric secretions to enter the lower air-
ways . Ventilator associated pneumonia (VAP) is a
complication in as many as 28% of patients who receive
mechanical ventilation. The incidence of VAP increases
with the duration of mechanical ventilation. Estimated
rates are 3% per day for the first 5 days, 2% per day for
days 6 - 10, and 1% per day after day 10 . The crude
mortality rate of VAP is 27% - 76%. Studies have con-
sistently shown that a delay in starting appropriate and
adequately dosed antibiotic therapy increases the mortal-
One of the causes of the high mortality rate is the di-
agnosis delay .
Unlike community-acquired pneumonia, it may be dif-
ficult to determine whether pneumonia has developed in
a hospitalized ventilator-dependent patient. Symptoms
and signs usually are not conclusive. Although the plain
chest roentgenogram remains an important component in
the evaluation of hospitalized patients with suspected
pneumonia, it is most helpful when it is normal and rules
out pneumonia. Microscopy evaluation and culture of
tracheal secretions and/or expectorated sputum are also
frequently inconclusive for patients clinically suspected
of having pneumonia, because the upper respiratory tract
*The authors declare no conflict of interest.
opyright © 2013 SciRes. OJRD
A. ABD EL HALIM ET AL.
of most patients in the ICU is colonized with potential
pulmonary pathogens, whether or not parenchymal pul-
monary infection is present . Procalcitonin (PCT) is a
peptide precursor of the hormone calcitonin, the latter
being involved with calcium homeostasis. It is composed
of 116 amino acids and is produced by parafollicular
cells (C cells) of the thyroid and by the neuroendocrine
cells of the lung and the intestine. The level of procalci-
tonin raises in a response to a proinflammatory stimulus,
especially of bacterial origin . Measurement of pro-
calcitonin can be used as a marker of sepsis caused by
bacteria and generally grades well with the degree of sep-
sis . PCT has the greatest sensitivity (85%) and speci-
ficity (91%) for differentiating patients with systemic
inflammatory response syndrome (SIRS) from those with
The aim of the work: was to clarify the role of the
serum procalcitonin in the diagnosis and the prognosis of
ventilator associated pneumonia.
2. Subjects and Methods
This study was conducted at the ICU of King Fahad Spe-
cialist Hospital, Dammam, Kingdom of Saudi Arabia.
The study was approved by Ethics and Research Com-
mittee. All patients or their families and control subjects
gave their written informed consent before participating
in the study. This study included 3 groups of subjects (Ta-
Group 1: It included 42 VAP patients that were ad-
mitted at the ICU. The mean age was 58.09 ± 13.07 years.
There were 27 (64.28%) males and 15 (35.72%) fe-
Group 2: It included 20 non VAP-ICU admitted pa-
tients (on mechanical ventilation). The mean age was
56.90 ± 10.54 years. There were 12 (60%) males and 8
Group 3: It included 20 healthy control subjects. The
mean age was 53.85 ± 11.26 years. There were 13 (65%)
males and 7 (35%) females.
The three groups were matched for age and sex (p val-
ue > 0.05)
All subjects included in this study were undergone for
1) Complete history taking and thorough physical ex-
2) Chest x ray examination.
3) Complete blood picture (CBC), C reactive protein
(CRP), liver and kidney functions tests.
4) Arterial blood gases analysis (ABGs).
5) Acute Physiology and Chronic Health Evaluation II
(APACHE II) score was calculated for patient groups
6) The Sequential Organ Failure Assessment score
Table 1. Some basal characteristic data for the subjects in-
cluded in this study.
(No = 42)
(No = 20)
(No = 20)
Age (Mean ±SD)
58.09 ± 13.07
160.4 ± 4.7
14.5 ± 3.53
24.11 ± 4.57
7.88 ± 2.92
56.90 ± 10.54
28.53 ± 2.6
9.6 ± 0.45
16 ± 3.25
3.56 ± 2.04
53.85 ± 11.26
5.38 ± 1.1
6.5 ± 1.04
(SOFA) was calculated for patient groups only.
7) The Clinical Pulmonary Infection Score (CPIS) was
calculated for patient groups only.
8) Measurement of procalcitonin: this was done in all
subjects included in this study. Blood samples were taken
and the sera were separated and stored at −80˚C for fur-
ther procalcitonin analysis. Procalcitonin levels were
determined with the commercially available automated
immunochemistry method (Brahms Kryptor, Brahms Li-
aison, Berlin, Germany) . For VAP patients; PCT
measurement was done on the first day of diagnosis (for
comparisons with other subject groups) and then repeated
on the 5th day of diagnosis.
Pneumonia was classified as VAP if it occurred after
48 hours of mechanical ventilation and was not incu-
bated before the initiation of the mechanical ventilation.
Early-onset VAP was defined as that occurring during
the first 4 days on mechanical ventilation, whereas VAP
developed thereafter was classified as late-onset . A
diagnosis of pneumonia was suspected when a new, per-
sistent infiltrate, consolidation, cavitation or pleural effu-
sion was seen on chest X-rays and at least two of the fol-
lowing were observed: a body temperature below 36˚C
or above 38˚C; a white blood cell count lower than
4000/mm3 or higher than 11,000/mm3; and macroscopi-
cally purulent tracheal aspirate. Tracheal aspirate was
classified as purulent or non purulent after visual inspec-
tion. Tracheal aspirate for quantitative culture had been
obtained before antimicrobial treatment was started. Tra-
cheal aspirate cultures yielding ≥105 CFU/ml were con-
sidered positive. We calculated the clinical pulmonary
infection score (CPIS). Patients were assumed to have
VAP when the CPIS was >6. Patients received a diagno-
sis of VAP only after other medical conditions to which
the presenting symptoms, signs or radiological findings
could be attributed had been ruled out. For all patients in
Copyright © 2013 SciRes. OJRD
A. ABD EL HALIM ET AL. 75
whom the clinical suspicion of VAP was confirmed, em-
pirical antimicrobial therapy was started immediately and
modified after culture results if needed. Patients were
followed until resolution of pneumonia or death .
2.1. Exclusion Criteria
Any patient has any one of the followings was excluded
from this study: 1) Age below 18 years; 2) The develop-
ment of pneumonia within 48 hours of beginning of me-
chanical ventilation; 3) Evidence of bacterial infection
elsewhere; 4) Immunosuppression; 5) Expected early
2.2. Statistical Analysis
Statistical analysis was performed with the Statistical
Package for the Social Sciences, version 16 for Windows
(SPSS Inc., Chicago, IL, USA). Values of p < 0.05 were
considered statistically significant.
The total duration of mechanical ventilation among pa-
tients with VAP was 15.35 ± 9.21 days compared with
10.67 ± 8.52 days in patients without VAP (p value <
0.01). There were 15 (35.71%) early onset VAP patients
and 27 (64.29%) late onset VAP patients. The causative
microbes among VAP patients were shown in Table 2.
There was a highly statistically significant difference
(p value < 0.001) between VAP patients on one side and
both non VAP-ICU patients and healthy control subjects
on the other side regarding the mean values of PCT (1.54
± 0.50 ng/ml among VAP patients, 0.06 ± 0.03 ng/ml
among non VAP patients, and 0.04 ± 0.02 ng/ml among
healthy control subjects) (Table 3 and Figure 1). No
statistically significant difference (p value > 0.05) in the
mean values of PCT was present between non VAP-ICU
patients and healthy control subjects (0.06 ± 0.03 ng/ml
among non VAP patients and 0.04 ± 0.02 ng/ml among
healthy control subjects) (Table 3 and Figure 1).
22 (52.38%) patients out of 42 VAP patients survived
while 20 (47.62%) patients died. No patient died in the
first 5 days after diagnosis. The mean values of PCT
were statistically significantly higher (p value < 0.001)
among died VAP group than the survivor VAP group on
both first day (1.92 ± 0.41 ng/ml vs 1.19 ± 0.29 ng/ml
respectively) and 5th day measurements (4.49 ± 0.59
ng/ml vs 0.81 ± 0.21 ng/ ml respectively) (Table 4 and
Figure 2). The mean values of PCT increased signify-
cantly from (1.92 ± 0.41 to 4.49 ± 0.59) among died
group while decreased significantly from (1.19 ± 0.29 to
0.81 ± 0.21) among the survivor group on repeated test-
ing on the 5th day in comparison with the first day meas-
urement (Table 4 and Figure 2). There was a high statis-
tically positive correlation (p value < 0.01) between mor-
Table 2. The microbiological profile among the VAP pa-
Microbes No of the VAP patients (%)
Table 3. Comparison between the different subject groups
regarding initial PCT levels (ng/ml).
Groups ( No) MinimumMaximum Mean ± SD p value
1. VAP patients
(No = 42) 0.65 2.82 1.546 ± 0.5091 vs 2 <
2. Non VAP
patient (No = 20)0.01 0.12 0.061 ± 0.0361 vs 3 <
3. Healthy control
subjects (No = 20)0.01 0.09 0.0438 ± 0.0272 vs 3 >
Table 4. Comparison of some measurements between the
survivor and died groups among VAP patients.
Outcome APACHEII SOFA CPIS PCT 1
(Mean ± SD)
(No = 20)
(Mean ± SD)
p value p < 0.01p < 0.001 p < 0.01 p < 0.001p < 0.001
tality prediction scores (APACHE II (R = 0.449), CRIP
(R = 0.403) and SOFA (R = 0.437)) and initial PCT se-
In this study, there was a highly statistically significant
difference (p value < 0.001) between VAP patients on
one side and both non VAP-ICU patients and healthy
control subjects on the other side regarding the mean
values of PCT (1.54 ± 0.5 ng/ml among VAP patients,
0.06 ± 0.03 ng/ml among non VAP patients, 0.04 ± 0.02
ng/ml among healthy control subjects). These results are
in agreement with that of other investigators. Lee JY, et
al.,  found that the PCT level in the patients with
pneumonia (2.06 ± 0.60 ng/ml) was significantly higher
than that in the healthy controls (0.05 ± 0.02 ng/ml). In
case-control study carried out by Polzen et al., 
which included 26 patients with pneumonia found higher
PCT levels among pneumonia patients with a cut-off of
Copyright © 2013 SciRes. OJRD
A. ABD EL HALIM ET AL.
Figure 1. Comparison between the different subject groups re-
garding initial PCT levels (ng/ml).
day PCT 5
Figure 2. Comparison of the mean PCT levels between the survivor
and died groups among VAP patients (first and 5th days respec-
0.5 ng/ml. Another study done by Müller and his col-
leagues  with a cohort of 373 subjects demonstrated
that PCT with an AUC of 0.85 (0.80 - 0.91) was associ-
ated with a diagnosis of pneumonia and that PCT im-
proved the ability of clinical findings to diagnose pneu-
monia (p < 0.001). This study postulated that a PCT <
0.1 ng/ml indicates another diagnosis than pneumonia
even with an infiltrate on X-ray. Bafadhel et al.  con-
ducted a cohort trial with 319 patients of whom 96 had
pneumonia. Patients with pneumonia had a higher PCT
(p < 0.0001) than those with acute exacerbation of
chronic obstructive pulmonary disease (AECOPD). At a
cut-off of 0.08 ng/ml, PCT had an AUC of 0.93 (0.88 -
0.98) for differentiation between pneumonia and COPD;
sensitivity 89% (95% CI 78 - 95) and specificity 78%
(95% CI 72 - 82). Likewise Seligman and his group 
found the biomarkers procalcitonin, MR-proANP, and
copeptin are increased among VAP patients and can pre-
dict mortality in VAP, as can the SOFA score. Procalci-
tonin alone has the greatest predictive power for such
There are accumulating data that explain our and other
researchers’ results. The investigations identified PCT as
part of the complex pro-inflammatory response of the
innate immune system . In vitro stimulation of
macrophages with either bacteria or endotoxin results in
rapid synthesis and release of PCT within 4 hours .
In a hamster model of Escherichia coli peritonitis, tran-
scription and translation of PCT synthesis was demon-
strated in virtually all organs tested and in macrophages
. In vitro , endotoxin stimulated adipocytes to synthe-
size PCT in the absence of macrophages, but synthesis
was augmented if adipocytes were incubated with en-
dotoxin-sensitized macrophages . PCT differs from
other biomarkers of the invasion by bacterial pathogens
by several aspects. Serum PCT serum levels are detect-
able as early as 3 - 4 h after invasion, which is much ear-
lier than the increase in the C-reactive protein level or
erythrocyte sedimentation rate . Also, elevated PCT
levels have not been noted for other inflammatory condi-
tions, such as acute respiratory distress syndrome, pol-
yarteritis nodosa, systemic lupus erythematosis [8-20].
Available data also indicate that PCT levels are not in-
fluenced by therapy with glucocorticoids or nonsteroidal
anti-inflammatory agents. PCT levels do not increase in
patients with infection due to respiratory viruses .
Our study revealed that the mean values of PCT were
statistically significantly higher (p value < 0.001) among
died VAP group than the survivor VAP group on both first
day (1.92 ± 0.41 ng/ml vs 1.19 ± 0.29 ng/ml respectively)
and 5th day measurements (4.49 ± 0.59 ng/ml vs 0.81 ±
0.21 ng/ml respectively). Other studies found similar
results. Duflo et al.  found PCT was significantly
elevated in non-survivors: the best cut-off for serum PCT
in the non-survivors in the VAP group was 2.6 ng/ml
with a sensitivity of 74% and a specificity of 75%. Like-
wise, Luyt et al.  found high median PCT levels of
about 3 ng/ml at Day 1 in patients with unfavorable out-
comes during the clinical course of microbiologically
proven VAP (n = 63). These results are explained intui-
tively by that the severe and non respondent pneumonia
among the died patients are associated with high bacte-
rial and toxin loads that stimulate excess release of the
In this study the mean values of PCT increased signi-
ficantly (from (1.92 ± 0.41 to 4.49 ± 0.59) among died
group while decreased significantly (from 1.19 ± 0.29 to
0.81 ± 0.21 among the survivor group on repeated testing
on the 5th day in comparison with the first day measure-
ment. Other studies showed similar results. Harbarth et
al.,  and Jensen and his colleagues  found that
unsuccessful source control and poor outcome is associ-
ated with persistent elevated PCT levels. Also Bloos et
al.,  found that high PCT levels are associated with
increased severity of illness in patients with severe pneu-
monia and appears to be a prognostic marker mortality
comparable to the APACHE II score. These results are
explained by that the severe and non respondent pneu-
Copyright © 2013 SciRes. OJRD
A. ABD EL HALIM ET AL. 77
monia among died patients are associated with sustained
high bacterial and toxins load that stimulate a continuous
release of the PCT. While survivors are associated with
continuous decrease of bacterial and toxin load with less
stimulation of PCT release.
Our study found a statistically positive correlation (p
value < 0.01) between mortality prediction scores
(APACHE II (R = 0.449), CRIP (R = 0.403) and SOFA
(R = 0.437)) and initial PCT serum levels. Similar ob-
servations were reported by Meisner et al.,  and by
Schroder et al.,  in critically ill patients. Hedlund et
al.,  showed that the severity of disease measured by
the APACHE II score was strongly associated with ad-
mission levels of PCT in 96 adult patients with CAP. In
study included 110 patients with pneumonia, Bousse-
key et al.,  found higher PCT levels in bacteremic
patients and/or septic shock patients (4.9 ng/ml vs 1.5
ng/ml) and in patients who developed infection-related
complications (septic shock, multiorgan dysfunction,
acute respiratory distress syndrome and disseminated
intravascular coagulation) during their ICU stay. Like-
wise, Bloos et al.,  found a significant association
between PCT levels and organ dysfunction as assessed
by the SOFA score. These results suggest that the PCT
level can be used as a prognostic factor among VAP pa-
There were some limitations in this study. The number
of subjects was small and therefore a study on a larger
number of subjects is needed.
This study found that the increased PCT serum level is
an important diagnostic tool for VAP and the PCT serum
levels can predict the outcome of VAP patients. We
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