PCT as a diagnostic and prognostic tool in burn patients.

Whether time course has a role in monitoring sepsis

treatment
A. Lavrentieva
a,
*, S. Papadopoulou
b
, J. Kioumis
c
, E. Kaimakamis
c
, M. Bitzani
a
a
Papanikolaou General Hospital, Burn ICU, Thessaloniki, Greece
b
Papanikolaou General Hospital, Burn Surgery Department, Thessaloniki, Greece
c
Papanikolaou General Hospital, Pulmonary Department, Thessaloniki, Greece
1. Introduction
Despite major advances in burn care and improved opportu-
nities for therapeutic intervention, the mortality rate of
patients with severe burn due to septic complications is still
considerable [1,2]. Early diagnosis of septic complications
following by early and adequate antibiotic therapy may
improve the survival rate of critically ill patients [3,4].
Since burn patients are in a state of chronic systemic
inammatory stimulation; and present non-specic symp-
toms of systemic inammation, traditional laboratory tests
and diagnostic criteria of SIRS and sepsis lack diagnostic
accuracy and are sometimes misleading. A consensus panel
for the American Burn Association (ABA) has developed
specic guidelines for the diagnosis of sepsis in burn patient
that include higher thresholds for certain parameters such as
temperature, heart rate and respiratory rate [5]. These guide-
lines also suggest the presence of thrombocytopenia, insulin
resistance, feeding intolerance, increased uid requirements
and other clinical indicators as markers of inammation and
infection. In addition to these clinical signs, documented
presence of infection and a clinical response to antimicrobials
are required. The consensus conference of the ABA, in an
attempt to improve the current denitions of sepsis, suggests
the use of procalcitonin (PTC) and the other inammatory
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3
a r t i c l e i n f o
Article history:
Accepted 29 August 2011
Keywords:
Sepsis
Localized infection
Procalcitonin
Diagnostic accuracy
a b s t r a c t
Objective: To evaluate the diagnostic and prognostic performance of inammatory markers
for septic and non septic (localized) bacterial infections in patients with severe burn.
Methods and results: Data of 145 patients were prospectively included in this study. Serum
procalcitonin and other inammatory markers were measured within 24 h after burn and
daily thereafter. Maximumprocalcitonin( p = 0.004) was independent predictors of outcome
in logistic regression analysis. PCT thresholds of 1.5 ng/ml, 0.52 ng/ml and 0.56 ng/ml had
adequate sensitivity and specicity to diagnose sepsis, respiratory tract and wound infec-
tions respectively. A threshold value of 7.8 ng/ml in PCT concentration on day 3 was
associated with the effectiveness of the sepsis treatment with an AUC of 0.86 (95% CI
0.691.03, p = 0.002). C-reactive protein levels and WBCs showed no signicant change over
the rst 3 days in the patients with successfully treated sepsis ( p = 0.93).
Conclusion: The maximum procalcitonin level has prognostic value in burn patients. PCT
can be used as a diagnostic tool in patients with infectious complications with or without
bacteremia during ICU stay. Daily consecutive PCT measurements may be a valuable tool in
monitoring the effectiveness of antibiotic therapy in burn ICU patients.
# 2011 Elsevier Ltd and ISBI. All rights reserved.
* Corresponding author at: Hadzipanagiotidi 2, Panorama, 55236 Thessaloniki, Greece. Tel.: +30 6949121458.
E-mail address: alavrenti@gmail.com (A. Lavrentieva).
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/burns
0305-4179/$36.00 # 2011 Elsevier Ltd and ISBI. All rights reserved.
doi:10.1016/j.burns.2011.08.021
markers in order to more comprehensively dene the
variations in individual response to burn and infection [5].
Procalcitonin measurement is now routinely used to
conrm bacterial infection in critically ill patients. Procalci-
tonin also seems to be a useful marker for the detection of
septic complications in burn patients [610]. Besides its role as
a marker of infection, procalcitonin has been shown to be
helpful in determining the effectiveness and appropriate
duration of antibiotic therapy in critically ill patients [11,12].
Evidence from clinical trials shows that the use of algorithms
based on PCT levels leads to an important reduction in
antibiotic use in critically ill patients [13,14]. However the role
of PCT in monitoring the effectiveness of antibiotic therapy in
burn ICU patients has not been reported, to our knowledge.
The diagnostic performance of PCT has also not been
evaluated for a variety of localized bacterial infections in
burns, such as lower respiratory tract infection, burn wound
and urinary tract infections. No reports have described the
PCT levels in sepsis caused by different types of microorgan-
isms (Gram negative and Gram positive).
The objectives of this study were:
To examine the accuracy of PCT to diagnose sepsis and
localized infectious complications in burn ICU patients and
to compare the diagnostic value of PTC with traditional
markers of inammation such as C-reactive protein (CRP)
and white blood cells count WBC).
To estimate the differences in PCT level according to the
type of microbial agent responsible for causing the infection.
To evaluate the ability of PCT to assess the effectiveness of
antibiotic therapy in these patients.
To evaluate the relationship of PCT levels to patients outcome.
2. Materials and methods
This prospective study was conducted between 2005 and 2010
and performed at the Burn Unit of G. Papanikolaou General
Hospital in Thessaloniki. The study protocol was approved by
the local ethic committee.
Patients: All consecutive patients admitted to our ICU were
included in this study. Exclusion criteria were: nonsurvivable
burn (decision for comfort care on admission) [n:15], admis-
sion for non-burn diagnosis (TEN, reconstructive surgery) [n:8],
admission for less than 72 h [n:19], age less than 18 years [n:2],
and burn size less than 20% of total burn surface area (TBSA)
[n:35].
We prospectively investigated data of 145 remaining
patients. Demographic and clinical data were recorded for
each patient. The APACHE II score (Acute Physiology and
Chronic Health Evaluation II) and SAPS II score (Simplied Acute
Physiological Score II) were used to grade illness severity. For the
diagnosis of multiple organ dysfunction or failure, the Sequen-
tial Organ Failure Assessment score (SOFA) was calculated daily
until discharge from ICU, maximum SOFA scores and ICU
mortality were also recorded. In all patients PCT and CRP
plasma concentrations and white blood cell count (WBC) were
measured daily during ICU stay (rst sample was performed
within the rst 24 h from admission). All patients had a urinary
catheter in place to monitor urine output.
2.1. Infection criteria
Each patient was examined for signs and symptoms of
infection at the time of admission and daily thereafter until
their discharge from the ICU or their death. Diagnosis of sepsis
and septic shock were performed according to the current
recommendations [5,15].
Diagnosis of localized infections (respiratory tract, burn
wound, urinary tract) were dened according to the American
Burn Association consensus conference recommendations as
well as by using additional criteria recommended in bibliog-
raphy [5,16,17].
Pneumonia was dened by the presence of a new or
progressive inltrate in addition to at least two out of three
clinical features (fever greater than 38 8C, leukocytosis or
leukopenia, and purulent secretions) plus a positive quantita-
tive culture of samples obtained either by bronchoalveolar
lavage, or by protected specimen brush, using diagnostic
thresholds of 10
4
colony forming units (CFU)/ml and 10
3
CFU/
ml respectively.
Catheter-associated urinary tract infection (CA-UTI) was
dened by the presence of signicant bacteriuria (10
5
CFU/
ml) with no more than 2 species of microorganisms in a
patient with signs and symptoms relative to the urinary tract.
Burn wound infections were characterized by the presence
of the following criteria: (a) clinical signs of wound infection
(purulent secretions, color changes, pain, erythema, unex-
pected change in the appearance and the depth of the wound,
conversion of partial sickness injury to full sickness necrosis,
non-viable grafts), and (b) burn wound biopsy with 10
5
colo-
ony-forming units/g tissue, or quantitative swab with counts
of 10
6
bacteria obtained from surface swab samples or a
histological diagnosis of burn wound infection based on the
observation of microorganisms invading viable tissue beneath
the eschar surface.
2.2. Laboratory measurement
Blood samples from patients were drawn from indwelling
arterial lines for measurement of CRP, PCT and routine
laboratory tests including WCC. Serum PCT levels were
determined by immunoluminometric assay (Lumitest PCT,
Brahms Diagnostica, Berlin, Germany). The lower detection
limit was 0.08 ng/ml. The CRP concentration was measured by
a Boehringer Mannheim (BM)/Hitachi automated immuno-
turbidimetric (Tuna-quant, BM, Germany) technique. The
lower detection limit was set at 0.2 mg/dl. White blood cell
(WBC) and platelet counts were determined by using an
automatic counter (Gene-s; Coulter, Paris, France). The normal
range for the WBC count was 430010,800 cells/mm
3
, the
normal range for the platelet count was 150,000450,000 cells/
mm
3
. The blood gas analyzer (Radiometer ABL 725 analyzer;
Radiometer A/S, Copenhagen, Denmark) directly measured
lactate levels. The range of normal serum lactate levels was
0.52.2 mmol/l.
2.3. Statistical analysis
Values are presented as median and interquartile range (IQR)
(25th to 75th percentiles), absolute value and percentage, or
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3 357
mean standard deviation. The nonparametric data were
compared with the MannWhitney U test, and categorical
variables were compared with the chi-square test. PCT kinetic
is expressed as delta PCT (DPCT) concentrations. DPCT was
calculated as the difference between concentrations on day 0
and 72 h (day 0 to 72 h). The sensitivity, specicity, and
positive likelihood ratio for PCT cutoff levels were calculated.
To determine the predictive ability of PCT receiver operating
characteristic (ROC) curves were constructed and the areas
under the curve (AUCs) were calculated with 95% condence
intervals (CIs). Analysis of the coordinate points of the ROC
curves revealed the best threshold values for prediction of
outcomes in each case based on the supreme combination of
sensitivity and specicity levels of each proposed threshold.
Correlations between inammation markers and TBSA were
studied using Pearson bivariate correlation coefcient. Logis-
tic regression analysis was used to examine the impact of
parameters on mortality. A p value of less than 0.05 was
considered to be statistically signicant in all tests. The
analyses were performed using SPSS 17.0 software (SPSS Inc.,
Chicago, IL, USA).
3. Results
Data of 145 patients were evaluated (48.2 18.3 years, 55%
male, 38.8 18% TBSA, 11.5 4 APACHE II, 29 10 SAPS II, 4.4
(26) SOFA). The mortality rate of patients was 16.5%. Multiple
organ failure due to septic complications was the main cause
of death. Concentrations of PCT at admission and maximum
PCT levels were 0.69 (0.31.4) ng/ml, and 7.8 (0.3139) ng/ml,
respectively. No correlations between TBSA and admission
PCT ( p = 0.299) or CRP ( p = 0.3) levels were observed. A
correlation between the maximum PCT and TBSA was found
(r = 0.87, p = 0.004). Maximum procalcitonin ( p = 0.004) and
maximum SOFA score ( p = 0.011) were independent predictors
of outcome in logistic regression analysis.
Sepsis of bacterial etiology was diagnosed in 86 out of 145
(59.3%) patients, 43 of whom had septic shock. The distribu-
tion of septic patients who met the clinical and laboratory
criteria of inammation and infection as they are specied by
American Burn Association consensus conference recom-
mendations was the following: temperature (>39 8C or
<36.5 8C) 58 (67.4%) patients; progressive tachycardia 82
(95.3%) patients; progressive tachypnea 69 (80.2%) patients;
thrombocytopenia 44 (51%) patients; hyperglycemia 68
(79%) patients, inability to continue enteral feedings for more
than 24 h 55 (64%) patients. Positive cultures were identied
in 75 patients with sepsis, 62 septic patients had a clinical
response to antibiotic therapy and in 3 patients the diagnosis
was conrmed with histological tissue analysis.
Patients with septic shock had signicantly higher SOFA
scores [8.9 (IQR, 313)] and PCT concentrations [23.9 ng/ml
(IQR, 1.634)] on day 1 of sepsis compared with patients
without septic shock [SOFA score-5.6 (IQR, 36), PCT-5.6 ng/ml
(IQR, 0.48)], p = 0.04, p = 0.001, respectively. No signicant
differences were found in CRP and WBCbetween patients with
and without septic shock.
Table 1 Inflammatory markers and SOFA score in sepsis, respiratory tract infection (with and without sepsis), burn
wound infection (with and without sepsis) and urinary tract infection.
PCT, median
(IQR), ng/ml
CRP, median
(IQR), mg/dl
WBC, median
(IQR), (10
9
l
1
)
Temp, median
(IQR), (8C)
SOFA, median
(IQR)
Sepsis (all septic patients, n:86) 7.2 (0.433) 17.65 (239) 14.6(233) 37.9 (3341) 7 (215)
Pre infection 0.44 (0.11.8) 12.0 (4.530.7) 12.7 (4.613.7) 37.7(3639) 3 (19)
p
*
<0.001 <0.001 0.004 0.198 <0.001
Sepsis (unknown etiology, n:11) 8.9 (0.621) 19.5 (1526) 15.4 (3.324) 38.5 (3539) 7.9 (414)
Pre infection 0.48 (0.21.2) 10.5 (626.8) 10.3 (516.5) 38.1 (35.539) 2.7 (27)
p
*
<0.001 <0.001 <0.01 0.07 <0.001
Blood stream infection (n:28) 10.4 (4.125) 24.3 (11.838) 18 (8.423) 38.6 (3840) 6.7 (58)
Pre infection 0.46 (0.21.8) 9.3 (712.8) 15.6 (8.913.5) 37.7 (3539) 3 (26)
p
*
<0.001 <0.001 0.07 0.06 0.01
Respir. tract infection (with sepsis, n:33) 6.3 (1.619) 23.6 (17.727) 12.2 (5.813) 37 (3338.5) 6 (59)
Pre infection 0.25 (0.10.4) 13.7 (11.515.4) 7.9 (5.811.4) 36.2 (3537.8) 4 (37)
p
*
<0.001 <0.001 <0.01 0.07 0.055
Respir. tract infection (without sepsis, n:24) 0.73 (0.14) 17.0 (10.538) 10.9 (2426.7) 38.1(3440) 5 (29)
Pre infection 0.38 (0.13.6) 16.150 (10.528.7) 9.9(4.818.5) 37.1(35.539) 3 (19)
p
*
0.011 0.743 0.48 0.013 <0.001
Wound infection (with sepsis, n:14) 4.5 (0.88) 13.5 (3.815.7) 20.5 (1124) 37.6 (3539) 6.3 (59)
Pre infection 0.4 (0.10.8) 10.8 (911) 10 (4.513) 38.6 (38 = 39) 2.6 (23)
p
*
<0.001 0.06 0.01 0.07 0.01
Wound infection (without sepsis, n:20) 0.87 (0.25.4) 18.5(1.938.50 13,400 (500031,000) 38.3 (3540) 3 (18)
Pre infection 0.35 (0.13.4) 11.0 (6.528) 10,640 (380022,300) 37.3(3640) 3 (17)
p
*
<0.001 0.12 0.05 0.329 0.177
Urinary tract infection (without sepsis, n:9) 0.36 (0.10.4) 14.2 (7.714.5) 11,360 (770023,500) 38.6 (3738.9) 2.5 (14)
Pre infection 0.2 (0.10.34) 12.9 (7.321.2) 10,500 (838013,500) 38.3 (3739) 2.4 (24)
p
*
0.545 0.237 0.411 0.359 0.9
PCT, procalcitonin; CRP, C-reactive protein; WBC, white blood cell count; Temp, temperature; SOFA, Sequential Organ Failure Assessment
score.
*
Differences between pre infection and infection levels.
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3 358
Out of 86 septic patients 11 had sepsis of unknown etiology,
33 patients had sepsis of respiratory tract etiology, 28 patients
had blood stream infection and 14 patients had burn wound
infection with sepsis. All patients with blood stream infection
met the ABA criteria of sepsis and were considered as septic
patients. No septic patients with urinary tract infection were
diagnosed.
Septic complications were caused by Gram negative
bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa,
Klebsiella pneumoniae, Proteus mirabilis) in 74.4% of patients
and were caused by Gram positive bacteria (Staphylococcus
aureus, Enterococcus faecium, Enterococcus faecalis), in 25.6% of
patients. Procalcitonin concentrations were lower in patients
with Gram positive sepsis (2.9 (0.44.7) ng/ml) compared to the
patients with Gram negative sepsis (8.2 (0.543) ng/ml),
p = 0.01.
Localized infections were diagnosed in 53 patients. The
types of localized infection were: respiratory tract infection in
24 patients (45.2%), burn wound infection in 20 patients (37.7%)
and urinary tract infection in 9 patients (17%). The main
bacterial strains responsible for infection were Gram negative
bacteria: P. aeruginosa, A. baumannii and K. pneumoniae.
Diagnosis of respiratory tract infection (with and without
sepsis) was conrmed by positive quantitative culture of
samples obtained by bronchoalveolar lavage (21 patients) and
by protected specimen brush (36 patients).
Diagnosis of wound infection was relied on clinical signs
of infection and culture data [burn wound biopsy (22
patients), quantitative swab (9 patients) and histological
ndings (3 patients)].
The levels of PCT were higher in patients with the diagnosis
of sepsis, respiratory tract infection and wound infection
compared to their preinfection concentrations (Table 1).
The performance of PCT in the diagnosis of septic and non
septic infectious complications is shown in Table 2, while the
ROC curve for PCT as a predictor for sepsis is shown in Fig. 1.
The selected value of 1.5 for PCT was based on the ROC
analysis since different PCT measurements led to slightly less
desirable sensitivity and specicity levels (values of 1.3 or 1.6
had sensitivity and specicity of 8890.4% or 82.595.2%,
respectively).
In 62 patients the sepsis was successfully treated, the
remaining 24 patients died due to septic complications and
multiple organ failure. Patients with treatment failure had
higher PCT levels on day 3 of treatment (19 ng/ml, IQR, 5.433)
as compared to the PCT values at the onset of sepsis (10.56 ng/
ml, IQR, 2.629), p = 0.001. C-reactive protein levels were also
increased on day 3 in patients with treatment failure [22 mg/dl
(IQR, 1533) vs. 28.2 mg/dl (IQR, 1849), p = 0.053]. The PCT
values were decreased in patients with successfully treated
sepsis, but the C-reactive protein levels showed no signicant
change over the rst 3 days in these patients ( p = 0.93) and
were decreased only after day 5 of the treatment (Table 3).
A substantial decrease in PCT concentration between the
rst and the second time points (day 1 vs. day 3, DPCT) was
Fig. 1 Receiver operating characteristic curve displaying
the diagnostic performance of PCT in sepsis.
Table 2 Diagnostic performance of PCT, in sepsis, and in localized infection.
Type of infection Sepsis,
n:86
Respiratory tract infection
(without sepsis), n:24
Wound infection
(without sepsis), n:20
Cut off value (ng/ml) 1.5 0.52 0.56
Sensitivity (%) 88.3 77.0 75.6
Specicity (%) 92.3 88.5 80.5
LR+ 11.47 7.67 4
LR 0.13 0.2 0.29
PPV (%) 91.8 88.5 80.0
NPV (%) 88.8 83.3 77.3
Diagnostic accuracy (%) 90.3 85.7 78.6
AUC 0.966 0.859 0.828
ROC signicance 0.0001 0.0001 0.0001
95% CI Lower 0.944 0.741 0.735
Upper 0.987 0.978 0.921
LR+, positive likelihood ratio; LR, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value; ROC, receiver
operating characteristics curve; AUC, area under ROC.
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3 359
associated with the effectiveness of sepsis treatment. The ROC
curves for PCT on the third day of sepsis treatment (PCT2)
revealed an optimum threshold value of 7.8 ng/ml predicting
the effectiveness of antibiotic therapy, with an AUC of 0.86
(95% CI 0.691.03, p = 0.002) (Fig. 2).
Concerning the DPCT, the ROC curve for the prediction of
the effectiveness of antibiotic therapy is displayed in Fig. 3,
with an AUC of 0.988 (95% CI 0.961.03, p < 0.001). The analysis
of the different possible thresholds showed that a value of
0 ng/ml is the optimum threshold for the prediction of therapy
success, meaning that any positive value of DPCT (any
reduction in two consecutive measurements) predicts positive
outcome, as opposed to negative values of DPCT (any increase
in PCT from the rst to the third day of sepsis).
4. Discussion
The value of PCT in diagnosing septic complications in burn
patients was examined in a number of trials [2,710,1820], the
ndings of which remain controversial. Most studies support
the usefulness of PCT as a diagnostic marker of sepsis in
critically ill burn patients. In a recent review of the value of
PCT for burns [6] it is reported that the primary inconsistency
in the burn specic studies is the reliance on the diagnostic
criteria for sepsis (ACCP/SCCM guidelines), which is intended
for a different ICU population. A consensus panel for the
American Burn Association has developed specic guidelines
for the diagnosis of sepsis in burn patients [5]. But up until now
Table 3 Time trend of parameters in patients with successfully treated sepsis.
Day 1 Day 2 Day 3 Day 5 Day 7
PCT (ng/ml) 19.1 (0.880.3) 14.6 (0.844) 7.7 (0.4635.7) 3.5 (0.213.4) 0.52 (0.25)
p 0.01
*
0.01
&
0.03
#
0.001
$
CRP (mg/dl) 20.7 (3.835.2) 18.7 (8.929) 18.4 (2.625) 14.1 (2.124.5) 10.2 (715)
p 0.93
*
0.61
&
0.023
#
0.001
$
WBC (10
9
l
1
) 14.2 (229) 15.4 (6.834) 17(5.134) 11.2 (728) 8.2 (4.415.9)
p 0.675
*
0.328
&
0.013
#
0.001
$
Temp. (8C) 38.2 (3540) 37.7 (35.339) 37.9 (3739) 37.9 (3739.8) 37.4 (3538.4)
p 0.465
*
0.136
&
0.732
#
0.2
$
SOFA 5.4 (37) 4.7 (27) 2.5 (15) 2.4 (15) 1.9 (13)
p 0.181
*
0.04
&
0.13
#
0.037
$
Lactate (mmol/l) 2.7 (1.14) 2.1 (0.93) 0.95 (0.51.9) 0.9 (1.51.5) 0.7(0.51.7)
p 0.075
*
0.08
&
0.153
#
0.09
$
PCT, procalcitonin; CRP, C-reactive protein; WBC, white blood cell count; Temp, temperature; SOFA, Sequential Organ Failure Assessment
score.
*
Day 1 vs. day 2.
&
Day 3 vs. day 2.
#
Day 5 vs. day 3.
$
Day 7 vs. day 5.
Fig. 2 Receiver operating characteristic curve for PCT of
7.8 ng/ml (on day 3) and effectiveness of sepsis treatment.
Fig. 3 Receiver operating characteristic curve for delta PCT
as a predictor of the effectiveness of sepsis treatment.
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3 360
the studies of PCT on burn patients have not reported any
additional criteria for sepsis diagnosis apart from the ACCP/
SCCM guidelines. To our knowledge this is the rst study on
PCT that uses these additional specic diagnostic criteria for
sepsis and localized infections in burn patients.
In our study increased levels of PCT were observed during
the rst 24 h after burn. There was no positive correlation
between the initial PCT level and the TBSA. This nding is in
agreement with the results of Neely et al. [2] who did not
observe any correlation between burn size and PCT level in
pediatric burn patients. Our study found a positive correlation
between the TBSA and maximum PCT levels, additionally, the
maximum procalcitonin level along with the maximum SOFA
score were independent predictors of ICU mortality in logistic
regression analysis. These ndings conrm that PCT mea-
surement reects the presence of septic complications, which
are the main reason for organ failure and death in burn
patients. Meisner et al. [21] also found that higher SOFA scores
were associated with higher PCT concentrations in 40 burn
patients. In a study of von Heimburg et al. [9] no positive
correlation between the PCT levels at admission and the TBSA
was found, but a positive correlation between the TBSA and
the mean peak PCT levels during the later days postburn
(r = 0.73, p < 0.05) was observed.
4.1. Procalcitonin in sepsis
We observed signicant increase in PCT in septic patients
compared to their preseptic levels. The median PCT concen-
trations were 7.2 ng/ml at the onset of sepsis and were as high
as 23.9 ng/ml in patients with septic shock. High PCT
concentrations in critically ill patients with septic shock have
been reported in other studies [2224]. The cutoff limit for PCT
is often set at approximately 0.53.0 ng/ml to differentiate the
sepsis from other causes of systemic inammatory response
in critically ill patients [10,19,22,25,26]. In our study a threshold
of 1.5 ng/ml seemed to be a reasonable value with adequate
sensitivity and specicity to diagnose septic complications in
burn patients.
PCT concentrations are reported to be inuenced by the
organism responsible for causing bacteremia [27,28]. A study
by Charles et al. [27] demonstrated a higher peak PCT value
when Gram negative organisms were identied as the cause of
infection, than when the infection was caused by Gram
positive organisms. In accordance to the previous data, our
patients with Gram negative sepsis also had higher PCT levels
compared to the patients with Gram positive sepsis.
In addition to the absolute PCT levels, the time course of
procalcitonin is also of diagnostic value [29]. Appropriate
antibiotic therapy is reported to cause rapid decline of PTC
levels [12,13]. Furthermore, evidence of the reduced use of
antibiotics was demonstrated when treatment was guided by
PCT levels in patients with suspected sepsis [14,30]. Only a few
studies have examined the changes of PCT levels closely over a
period of time in order to assess the appropriateness of the
antibiotic therapy in septic burn patients. A retrospective
study by Sachse et al. [8] describes a 1.5 ng/ml rise in daily PCT
levels associated with the onset of septic events. In our study
PCT levels started to decline in patients who were responding
to the antibiotic treatment from day 3 of treatment. On the
contrary, the PCT levels remained constantly elevated in the
24 patients who died from multiple organ failure induced by
sepsis. These ndings suggest that PCT may improve the
ability of clinicians to assess the effectiveness of antibiotic
therapy in burn patients at an early point in the course of
infection. Our results suggest that PCT measurements may
also be used to determine the duration of antibiotic treatment
in burn patients.
We observed an increase in CRP and WBCs in patients with
sepsis compared to their preseptic levels, but were unable to
observe any change in these markers of inammation in
patients with localized (non septic) infectious complications.
The CRP and WBCs did not decline until day 5 in patients with
appropriate antibiotic therapy. Several investigators reported
the persistently high levels of CRP in burn patients and the
absence of changes in septic complications [9,18,20]. In
addition, it is not clear whether the increase of CRP and
WBCs in burn patients is related to the presence of septic
complications or is an effect of thermal trauma itself and the
presence of inammation [5,7,8,18].
4.2. Localized infections
The superior diagnostic performance of PCT has been
evaluated for a variety of localized infections, in critically ill
patients [11,13,31,32]. A study by Benador et al. [32] describes
the usefulness of PCT in detecting urinary tract infections.
Procalcitonin seems to be useful tool to guide the antibiotic
therapy in community acquired pneumonia [11]. Data on the
clinical use of PCT measurement for the diagnosis of localized
infections in burn patients are lacking. The main site of
infection in our patients was the respiratory tract, followed by
wound infection, a few cases of urinary tract infection were
also observed. Patients with localized infections (without
bacteremia), had lower PCT levels compared to patients with
generalized infections and positive blood cultures. Patients
with respiratory tract infection and wound infection showed a
signicant increase in PCT concentrations compared with
their preinfection levels. The satisfactory diagnostic perfor-
mance of PCT in respiratory tract and burn wound infections
leads to the conclusion that PCT may also be used as a marker
of non bacteremic infectious complications in burn patients.
Although we did not note any changes in PCT level in patients
with urinary tract infection, the relatively small number of
cases limits the value of this observation. One of the questions
that could be raised by the study is the method used to
diagnose burn wound infection. A number of cases of wound
infection were diagnosed using quantitative swab, a method
that is not universally accepted. Despite the discussion
surrounding this method it has been proposed as viable in
bibliography [5,33].
5. Conclusion
The maximum procalcitonin level has prognostic value in
burn patients. PCT can be used as a diagnostic tool in patients
with infectious complications with or without bacteremia
during ICU stay. Daily consecutive PCT measurements may be
a valuable tool in monitoring the effectiveness of antibiotic
b ur ns 3 8 ( 2 0 1 2 ) 3 5 6 3 6 3 361
therapy in burn ICU patients. Properly designed studies are
needed to show whether both mortality rates and cost can be
reduced using PCT measurements to guide antimicrobial
treatment for burns.
Conict of interest statement
None.
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