Procalcitonin as an Early and Reliable Marker of Neonatal Sepsis

INTRODUCTION: Infection as a prime cause or a complication of other illness is the major cause of mortality and morbidity throughout the world in neonates. Early recognition, diagnosis and treatment of serious infections in the neonates are mandatory because of poor defense; newborn cannot localize the pathogens, which can easily spread to multiple organs. Lack of intervention at an early stage leads to mortality or severe sequelae. Progression from mild symptoms to death occurs more rapidly1. Most neonatal bacterial infections have an early bacteraemic phase preceding the development of full blown septicemia or localization of infection in organs and tissues. During this phase the clinical signs are subtle, but this is when the treatment must be started if there is to be intact survival. Neonatal sepsis is classified into early onset sepsis and late onset sepsis. Early onset sepsis (EOS): It develops within 72hrs of life. Organisms present in genital tract or in labour room and operation theatre are most common causes. Most cases are due to gram negative organisms like E.Coli, Klebsiella and Enterobacter species in our country. Late onset sepsis (LOS): It develops after 72 hrs of life due to community or hospital acquired infection. Two third of LOS is caused by gram negative organisms such as Klebsiella pneumoniae, Enterobacter, E.Coli, Pseudomonas aeruginosa, Alcaligenes faecalis, Salmonella typhimurium, Proteus, Citrobacter and Serratia. Rest is caused by gram positive organisms such as Coagulase negative staphylococcus (CONS) and Staph aureus. OBJECTIVES: Primary objective: Procalcitonin as an early and reliable marker of neonatal sepsis Secondary objective: To compare the effectiveness of CRP and WBC with procalcitonin in predicting the neonatal sepsis at the earliest. DISCUSSION: The major cause of neonatal morbidity and mortality is neonatal sepsis. This study was conducted to show Procalcitonin can be used as an early and reliable marker of neonatal sepsis and to compare its efficacy with that of CRP and WBC count. These two tests are routinely used in our institution for initial sepsis screening. If CRP and WBC count are as efficacious as procalcitonin, they can be substituted for procalcitonin in resource poor setting and cost effective. This study was conducted in 50 neonates who had clinical features of sepsis. Both preterm and term neonates were included. Both early onset sepsis and late onset sepsis were included. Blood samples were drawn for CRP, PCT, WBC count and blood culture before starting antibiotics. Other investigations like CSF analysis, CXR were done in symptomatic infants. Out of 50 neonates blood culture was positive in 27 (54%) neonates. 15 out of remaining 23 infants had other positive investigations like CSF analysis, CXR supporting sepsis and hence grouped as culture negative sepsis. Remaining 8 neonates had only clinical features and hence termed as suspected sepsis. Procalcitonin was positive (≥2ng/dl) in 35 neonates, CRP was positive (≥1mg/dl) in 25 neonates and WBC count was positive ( 20,000) in 22 neonates. Sensitivity, specificity, positive predictive value and negative predictive value are calculated for PCT, CRP and WBC count taking blood culture as gold standard test. The sensitivity, specificity, positive predictive value and negative predictive value for procalcitonin were 92.59%, 56.52%, 71.4% and 86.6% respectively. The sensitivity, specificity, positive predictive value and negative predictive value for CRP were 55.55%, 56.52%, 60% and 52% respectively. The Sensitivity, specificity, positive predictive value and negative predictive value for WBC count were 40.74%, 52.17%, 50% and 42.85%. Procalcitonin had highest sensitivity (92.59%) compared to that of CRP (55.55%) and WBC count (40.74%). The specificity of procalcitonin (56.52%) was almost same as that of CRP, but greater than the specificity of WBC count (52.17%) and lesser than that of platelet count (86.95%). The positive predictive value (71.4%) and negative predictive value (86.6%) of procalcitonin were higher than positive and negative predictive value of CRP and WBC count, which were (60%, 52%) and (50% and 42.85%) respectively. CONCLUSION: 1. Procalcitonin can be used as an early and reliable marker of neonatal sepsis. 2. CRP and WBC count though can be used as initial sepsis screening; it cannot be substituted for procalcitonin. 3. No combined investigation excluding procalcitonin was superior to procalcitonin. 4. Combination of procalcitonin and CRP had highest sensitivity but low specificity. 5. Combination of procalcitonin and platelet had both higher sensitivity and specificity. 6. Sampling interval greatly influence the level of CRP but not procalcitonin level. 7. Klebsiella Pneumoniae is the most common organism causing both early onset and late onset sepsis in our institution