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The Indian Journal of Pediatrics

https://doi.org/10.1007/s12098-018-2659-3

CLINICAL BRIEF

A Comparative Evaluation of Presepsin with Procalcitonin and CRP


in Diagnosing Neonatal Sepsis
Neeraj Kumar 1 & Rajeshwar Dayal 1 & Pratibha Singh 1 & Sunit Pathak 2 & Vishal Pooniya 3 & Ankur Goyal 4 & Raj Kamal 5 &
K. K. Mohanty 5

Received: 15 October 2017 / Accepted: 7 March 2018


# Dr. K C Chaudhuri Foundation 2018

Abstract
The objectives of this study were to study the clinical and biochemical profile of neonates with sepsis and to evaluate the
diagnostic role of presepsin and its comparison with C-reactive protein (CRP) and Procalcitonin (PCT). This study was con-
ducted from March 2015 through October 2016 in Neonatal intensive care unit (NICU) at S N Medical College, Agra. Neonates
with ≥1 clinical features of sepsis and/or two risk factors were included. A total of 41 cases and 41 controls were taken. Blood
sample was taken for all investigations. ROC curve analysis was performed. Out of 41 cases, 19 were blood culture positive,
majority were males (68.3%), low birth weight (LBW: 70.7%) and preterms (53.6%). At chosen cut-off values, sensitivity of
CRP, PCT and presepsin was 80.5%, 80.5%, 97.6% and specificity was 97.5%, 80.5%, 95.1% respectively. PCT and CRP were
comparable as diagnostic markers of neonatal sepsis. Presepsin, in comparison with CRP and PCT has better sensitivity and
negative predictive value (NPV).

Keywords CRP . Procalcitonin . Presepsin . Comparison . Neonatal . Sepsis

Introduction association with infection. The objectives of this study were


to study the clinical and biochemical profile of neonates with
Sepsis is one of the most important cause of neonatal morbid- sepsis and to evaluate the diagnostic role of presepsin in com-
ity and mortality. Result of blood culture is available after 24– parison to C-reactive protein (CRP) and Procalcitonin (PCT).
72 h. The current trend may lead to antibiotic overuse, in-
creased resistance and increased health costs [1]. sCD14-sub-
type, a 13 kD truncated N- terminal fragment of 64 amino acid
residues is called as presepsin. Presepsin is produced in Material and Methods

This cross-sectional study was conducted from March 2015


through October 2016 at Neonatal intensive care unit (NICU)
of a tertiary care hospital. Neonates with ≥1 features of sepsis
and/or two risk factors were included. Clinical features of
* Pratibha Singh sepsis include – Refusal to feed, feeding intolerance, lethargy,
headysmc06@gmail.com irritability, high pitched cry, seizures, hypotonia, temperature
instability, apnea, respiratory distress, poor perfusion,
1
Department of Pediatrics, Sarojini Naidu Medical College, tachypnea, bradycardia, abdominal distension, necrotizing en-
Agra, India terocolitis, vomiting, sclerema and mucosal bleeding. Risk
2
Department of Pediatrics, FH Medical College, Tundla, India factors considered were – Maternal fever within 2 wk prior
3
Department of Pediatrics, King George’s Medical University, to delivery, premature rupture of amniotic membrane (PROM)
Lucknow, India (>18 h), foul smelling and/or meconium stained liquor, single
4
Department of Microbiology, Sarojini Naidu Medical College, unclean or > 3 sterile vaginal examinations during labour,
Agra, India prolonged labor (sum of 1st and 2nd stage of labour >24 h),
5
Department of Clinical Medicine, National JALMA Institute for low birth weight (<2500 g), premature birth (<37 wk) [2].
Leprosy and other Mycobacterial Diseases (ICMR), Agra, India Infants who were already on antibiotics or those who
Indian J Pediatr

developed signs of sepsis within 72 h of discontinuation of sCD


antibiotics, those with congenital anomalies or severe birth 100
asphyxia were excluded. A total of 41 cases and 41 controls
(with no clinical and laboratory evidence of sepsis) were 80
included. Before initiation of antibiotics, blood samples

Sensitivity
were obtained. CRP was done by the rapid latex aggluti- 60
nation method. PCT and presepsin levels were determined
by using specific ELISA development kits. Receiver oper- 40
ating characteristic (ROC) curve analysis was performed to
determine cut-off levels for diagnosing sepsis. Statistical 20
analysis was performed using Microsoft excel 2013 and
SPSS trial version 22. 0
0 20 40 60 80 100
100-Specificity
Results Fig. 1 ROC curve of presepsin. AUC was 0.9. Sensitivity and specificity
was 97.6% and 95.1% respectively at presepsin level of 1800 μg/dl.
Out of 41 sepsis cases, 19 were blood culture positive (BCP) (Sample size = 82; p value <0.0001).
and 22 were suspected of having sepsis based on clinical and
laboratory findings but culture was negative (BCN). Baseline
characteristics of neonates included in the study are shown in
Table 1. Among 19 BCP cases, there were 7(36.8%) Gram Significant difference (p < 0.0001) was noted in levels of all
positive, 11(57.8%) Gram negative and 1(5.3%) Fungal iso- three biomarkers among patients and controls.
late. Most common organism isolated was Staphylococcus
aureus in 6 (31.5%) cases, followed by Klebsiella and E.coli
in 4(21%) and 3(15.7%) cases respectively. Discussion
Area under curve (AUC) for CRP was 0.8 with sensitivity
and specificity, 80.5%, 97.5%, respectively at a cut-off value Blood culture was positive in 19 (46.3%) cases which is com-
of 3.2 mg/dl. AUC for PCT was 0.8 with both sensitivity and parable to a previous study [3]. The common organisms iso-
specificity of 80.5% at a cut-off value of 0.2 ng/ml. AUC for lated were similar to another study [4]. The results of CRP,
presepsin was 0.9 with sensitivity and specificity, 97.6%, PCT and presepsin are shown in Table 2. Abdollahi et al.
95.1%, respectively at a cut-off value of 1800 μg/l (Fig. 1). reported lower sensitivity and higher specificity of CRP [5].

Table 1 Baseline characteristics


of neonates included in the study Characteristic Category Cases (n = 41) Controls (n = 41)
No. (%) No. (%)

Gender Male 28(68.3) 25(60.9)


Female 13(31.7) 16(39)
Birth weight < 2.5 kg 29(70.7) 27(65.8)
≥ 2.5 kg 12(29.2) 14(34.1)
Gestational age Preterm(< 37 wk) 22(53.6) 23(56)
Term(≥ 37 wk) 19(46.3) 18(43.9)
Onset of sepsis Early onset <72 h 24(58.5)
Late onset >72 h 17(41.4)
Maternal risk factors PROM (> 18 h) 13(54.1)
Multiple PV examination 5(20.8)
Foul smelling liquor 4(16.6)
Prolonged labor 3(12.5)
Maternal fever 2(8.3)
Clinical presentation Lethargy and refusal to feed 16(39)
Respiratory distress 14(34.1)
Seizures 12(29.2)
Indian J Pediatr

Table 2 Comparison of
diagnostic value of CRP, PCT and Sensitivity Specificity PPV NPV
presepsin
Overall BCP BCN EOS LOS

CRP 80.5% 84.2% 77.3% 75% 88.2% 97.5% 91.67% 82.61%


Procalcitonin 80.5% 100% 63.6% 79.2% 82.4% 80.49% 76.74% 79.49%
Presepsin 97.6% 100% 95.5% 100% 94.1% 95.12% 90.19% 97.37%

BCP Blood culture positive; BCN Blood culture negative; EOS Early onset sepsis; LOS Late onset sepsis; PPV
Positive predictive value; NPV Negative predictive value; CRP C-reactive protein

Sensitivity of CRP was more in late onset sepsis (LOS) Contributions NK and RD: Planned the study; PS: Collected and ana-
lyzed the data; KKM and AG: Laboratory measurements were super-
(88.2%) as compared to early onset sepsis (EOS) (75%). vised; SP, VP and RK: Data was interpreted. All authors approved the
Low sensitivity of CRP during the early phases of sepsis is final draft. RD will act as guarantor for this paper.
its known limitation. The authors found significant difference
(p < 0.0033) in sensitivity of PCT in BCP cases (100%) com- Compliance with Ethical Standards
pared to BCN cases (63.6%). The sensitivity of PCT was more
in LOS (82.4%) as compared to EOS (79.2%). PCT is phys- Conflict of Interest None.
iologically elevated during first 3 d of life. It has been found to
be a reliable marker of LOS. Motalib et al. found that at a cut-
off value of 672 pg/ml, presepsin had sensitivity, specificity,
of 97% and 98% respectively and that it was more sensitive References
and specific than CRP for diagnosis of EOS [6]. In the present
study, authors found, sensitivity of presepsin to be more in 1. Magudumana MO, Ballot DE, Cooper PA, et al. Serial interleukin 6
EOS (100%) as compared to LOS (95.5%). In a Japanese measurements in the early diagnosis of neonatal sepsis. J Trop
Paediatr. 2000;46:267–71.
study, the sensitivity of presepsin, PCT, IL-6 and blood culture
2. Takkar VP, Bhakoo ON, Narang A. Scoring system for the prediction
was found to be 91.9%, 89.9%, 88.9%, and 35.4% respective- of early neonatal infections. Indian Pediatr. 1974;11:597–60.
ly [7]. A previous study has shown that while PCT is a good 3. Chacko B, Sohi I. Early onset of neonatal sepsis. Indian J Pediatr.
sepsis marker, it was not statistically more accurate than CRP 2005;72:23–6.
[8]. The heterogeneity of results among various studies can be 4. Karthikevan G, Premkumar K. Neonatal sepsis: Staphylococcus
explained by use of kits employing different methods. aureus as the predominant pathogen. Indian J Pediatr. 2001;68:
715–7.
5. Abdollahi A, Shoar S, Nayyeri F, Shariat M. Diagnostic value of
simultaneous measurement of procalcitonin, interleukin-6 and hs-
Conclusions CRP in prediction of early-onset neonatal sepsis. Mediterr J
Hematol Infect Dis. 2012;4:e2012028.
PCT has better diagnostic value than CRP especially in BCP 6. Motalib TA, Khalaf FA, Hendawy GE, Kotb SE, Ali AA, Sharnoby
AE. Soluble CD14-subtype (prespsin) and hepcidin as diagnostic
cases. Specificity of CRP is more than PCT. Presepsin has the and prognostic markers in early onset neonatal sepsis. Egyptian J
best sensitivity and NPV and hence can detect most cases and Med Microbiol. 2015;24:45–52.
will lead to decrease in number of patients treated unnecessar- 7. Endo S, Suzuki Y, Takahashi G, et al. Usefulness of presepsin in the
ily. The authors recommend, presepsin should be used diagnosis of sepsis in a multicenter prospective study. J Infect
Chemother. 2012;18:891–7.
alongwith blood culture for diagnosing neonatal sepsis.
8. Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar AN, Gmeiner-
Presepsin, if introduced in laboratories as a routine investiga- Stopar T, Derganc M. Neutrophil and monocyte CD64 indexes, li-
tion would fall in the same price range as PCT. However, popolysaccharide binding protein, procalcitonin and C-reactive pro-
further studies pooling data from multiple centers are needed tein in sepsis of critically ill neonates and children. Intensive Care
before drawing definite conclusions. Med. 2009;35:1950–8.

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