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• The value of C-Reactive Protein in treatment decisions for early onset neonatal sepsis
  Sujoy Banerjee, Nitin Goel
  Published on: 14 October 2019
• Using the Kaiser -Permanente (KP) sepsis calculator to assess possible reduction in screening for early onset neonatal sepsis (EONS)- a prospective modelling study in the north-west
  Amitava Sur, Jayanthi Murali, Shanmuga Sundaram, Sandeep Dharamraj and Donna Porter
  Published on: 30 July 2019

• Published on: 14 October 2019

  The value of C-Reactive Protein in treatment decisions for early onset neonatal sepsis

  • Sujoy Banerjee, Consultant Neonatologist Singleton Hospital, Swansea
  • Other Contributors:
    • Nitin Goel, Consultant Neonatologist

  Dear Editor
  We read with interest the letter by Sur et al in response to our article (1). It was very reassuring to note that our findings were replicated in their study confirming the potential scale of antibiotic reduction while identifying all ‘blood culture positive’ sepsis. We did not collect data on CRP in our study. The evidence does not support a single CRP measurement as a reliable tool to help decisions to initiate treatment in the context of early onset neonatal sepsis (EOS), particularly in asymptomatic infants[2]. Consistent normal values over first 48 hours are associated with absence of EOS; but abnormal values in an asymptomatic infant are unreliable to predict culture proven sepsis [2-5]. CRP concentrations increase in neonates in response to a number of non-infective inflammatory conditions such as asphyxia, meconium aspiration, tissue trauma and pneumothorax. Serial CRP trend is irrelevant in treatment initiation decisions, and in low incidence conditions such as EOS, its value in predicting true culture positive EOS is below that is expected of a good and reliable test (Likelihood ratio 3.0)[4,6). The American Academy of Paediatrics states that diagnosis of EOS cannot be made using CRP in the absence of positive blood or CSF culture [2]. For asymptomatic low / moderate risk infants (currently treated with presumptive antibiotics), a period of observation / serial physical examination may be used instead of invasive tests to identify at an early...

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  Dear Editor
  We read with interest the letter by Sur et al in response to our article (1). It was very reassuring to note that our findings were replicated in their study confirming the potential scale of antibiotic reduction while identifying all ‘blood culture positive’ sepsis. We did not collect data on CRP in our study. The evidence does not support a single CRP measurement as a reliable tool to help decisions to initiate treatment in the context of early onset neonatal sepsis (EOS), particularly in asymptomatic infants[2]. Consistent normal values over first 48 hours are associated with absence of EOS; but abnormal values in an asymptomatic infant are unreliable to predict culture proven sepsis [2-5]. CRP concentrations increase in neonates in response to a number of non-infective inflammatory conditions such as asphyxia, meconium aspiration, tissue trauma and pneumothorax. Serial CRP trend is irrelevant in treatment initiation decisions, and in low incidence conditions such as EOS, its value in predicting true culture positive EOS is below that is expected of a good and reliable test (Likelihood ratio 3.0)[4,6). The American Academy of Paediatrics states that diagnosis of EOS cannot be made using CRP in the absence of positive blood or CSF culture [2]. For asymptomatic low / moderate risk infants (currently treated with presumptive antibiotics), a period of observation / serial physical examination may be used instead of invasive tests to identify at an early stage the very few who develop sepsis(7, 8).
  References:
  1. Goel N, Shrestha S, Smith R, et al. Screening for early onset neonatal sepsis: NICE guidance-based practice versus projected application of the Kaiser Permanente sepsis risk calculator in the UK population. Arch Dis Child Fetal Neonatal Ed. 2019 Online First Jul 11. DOI: 10.1136/archdischild-2018-316777.
  2. Puopolo KM, Benitz WE, Zaoutis TE. AAP Committee on Fetus and Newborn, AAP Committee on Infectious Diseases. Management of Neonates Born at ≥35 0/7 Weeks’ Gestation with Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. 2018;142(6):e20182894
  3. Mukhopadhyay S, Puopolo KM. Risk assessment in neonatal early onset sepsis. Semin Perinatol. 2012 Dec; 36(6):408-15.
  4. Benitz W.E., Han M.Y., Madan A., et al: Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 1998; 102: E41.
  5. Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis. Clin Perinatol. 2010;37: 421–438.
  6. Neonatal infection (early onset): antibiotics for prevention and treatment. Clinical guideline [CG149]. Published August 2012.https://www.nice.org.uk/guidance/cg149/evidence/full-guideline-pdf-18817....
  7. Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, et al. A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis. JAMA Pediatr.2017 Apr 1;171(4):365-371.
  8. Berardi A, Tzialla C, Travan L et al. Secondary prevention of early-onset sepsis: a less invasive Italian approach for managing neonates at risk. Ital J Pediatr. 2018; 44: 73

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  Conflict of Interest:
  None declared.

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• Published on: 30 July 2019

  Using the Kaiser -Permanente (KP) sepsis calculator to assess possible reduction in screening for early onset neonatal sepsis (EONS)- a prospective modelling study in the north-west

  • Amitava Sur, Neonatal consultant East Lancashire Hospital NHS Trust
  • Other Contributors:
    • Jayanthi Murali, Neonatal staff grade
    • Shanmuga Sundaram, Neonatal consultant
    • Sandeep Dharamraj, Neonatal consultant
    • Donna Porter, Advanced neonatal nurse practitioner

  We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline di...

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  We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline differences in maternal sepsis rates among geographical areas have an impact of the sensitivity of the calculator. It will be helpful and interesting to know whether the authors of this study and also previously reported ones (1) had similar experience with CRP and how they addressed the issue.

  Reference :
  1. Davidson SL, KIng R, et al. The Kaiser-Permanente early onset sepsis calculator – a tool to reduce antibiotic use in the UK? Neonatal Society summer meeting 2016.

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  Conflict of Interest:
  None declared.

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