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• Re:Procalcitonin for early diagnosis of neonatal nosocomial sepsis
  Cinzia Auriti
  Published on: 22 March 2016

• Published on: 22 March 2016

  Re:Procalcitonin for early diagnosis of neonatal nosocomial sepsis

  • Cinzia Auriti, Neonatologist
  • Other Contributors:
    • Vincenzo M. Di Ciommo

  Dear Editor, Thank you for the opportunity of answering to the comments of Chiesa (1) about our paper (2). First, the assay: Procalcitonin (PCT) was measured with an immunoluminometric, quantitative method, as in studies cited by us and by Chiesa. We used reagents Brahms and Berthold LB9507 luminometer (Dasit). The analytical signal, proportional to the concentration of the PCT in the sample, was converted into continuou...

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  Dear Editor, Thank you for the opportunity of answering to the comments of Chiesa (1) about our paper (2). First, the assay: Procalcitonin (PCT) was measured with an immunoluminometric, quantitative method, as in studies cited by us and by Chiesa. We used reagents Brahms and Berthold LB9507 luminometer (Dasit). The analytical signal, proportional to the concentration of the PCT in the sample, was converted into continuous concentration values. The definitive results were available in 5-6 hours from the blood collection, that we considered as "fast".

  Second: the first blood sample was taken on admission of all patients to NICU (time 0), in the absence of clinical and laboratory signs of infection, to check the increase of PCT during the subsequent infection, when it would be manifested. These results were never included in the calculation of the maximum value of PCT during infection. Infants with maternal-fetal infections were excluded from the study. In neonates who developed signs of nosocomial sepsis at least 48 h after the admission in NICU, PCT levels were further measured, as stated in the methods, at least within 24 and 48 h after the onset of the infection. These data only were used to calculate the median value of the highest PCT levels during the infection. PCT was also measured in 762 (GA 34+/-4 weeks, BW 2130+/-863 g) critically ill, but uninfected, patients; 205 of them were VLBW (29+/-3 weeks, BW 1123+/-258g), admitted to NICU in the first three days of life. Our unpublished data confirm a physiologic increase in PCT levels during the first days of life (3-5). Considering all uninfected neonates, the median values of PCT by day of life were: 0.40 ng/ml (IQR 0.21-1.20), in the first , 2.38 ng/ml (IQR 0.77-8.76), in the second and 0.52 ng/ml (IQR 0.28 -1.37), in the third. We obtained similar results in VLBW infants. Stratifying for BW (collinear with gestational and postnatal age), the accuracy of PCT did not differ significantly in neonates with a BW 1500- 2500 gr from that of heavier BW: a cut-off of 2.4 ng/ml. yielded a sensitivity of 55%, a specificity of 84% and a positive Likelihood Ratio of 3.4. Finally, in the first study of Chiesa, cited in his letter, (3) PCT was measured in healthy neonates, and a nomogram was established with statistical cut-offs. Despite this, when the problem of late-onset sepsis was investigated, a matched case-control design was adopted. (4) In this study cases and controls were defined, on clinical grounds, as we did, apparently ignoring statistical cut-offs and postnatal age, that was one of the variables of matching. Turner introduced as well a nomogram by gestational age in the first 4 days of life (5). However he has published results about PCT accuracy in another study (6), with the current, evidence-based approach, where different cut-offs were explored to establish the most appropriate for clinical application in a given context,. A number of biological or clinical reasons (e.g. concomitant diseases, age, labour, drugs etc.) can lead to misdiagnosis, measured by sensitivity, specificity and the other values of accuracy, that we hold as meaningful with our approach.

  Dr.ssa Cinzia Auriti Dr. Vincenzo M. Di Ciommo

  1). Chiesa C, Pacifico L, Osborn JF, Natale F, De Curtis M Procalcitonin for early diagnosis of neonatal nosocomial sepsis Arch Dis Child Fetal Neaonatal Ed Published 31 March 2011 2). Auriti C, Fiscarelli E, Ronchetti MP, at al. Procalcitonin in detecting neoanatal nosocomial sepsis. Arch Dis Child Fetal Neaonatal Ed 2011.Published online First: 15 March 2011 doi:10.1136/adc.2010.194100 3) Chiesa C, Panero A, Rossi N, et al. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26:664-72. 4) Chiesa C, Natale F, Pascone R, et al. C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta 2011; 412: 1053-59 5) Turner D, Hammerman C, Rudensky B, et al. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 2006;91:F283-6 6) Turner D, Hammerman C, Rudensky B, et al. The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants. Acta Paediatr 2006;95:1571-6

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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