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• In response to: Early onset neonatal sepsis: diagnostic dilemmas and practical management.
  Job LB Gieling
  Published on: 22 March 2016
• Re: I know you don't like our American brand of English, but......
  Alison Bedford Russell
  Published on: 22 March 2016
• I know you don't like our American brand of English, but......
  Barry M Perlin
  Published on: 22 March 2016

• Published on: 22 March 2016

  In response to: Early onset neonatal sepsis: diagnostic dilemmas and practical management.

  • Job LB Gieling, Pediatric resident
  • Other Contributors:
    • C Kramers, HWHA Fleuren, GPJM Gerrits, and BA Semmekrot

  We read with interest the review by AR Bedford Russell and F Kumar[1] about challenges in diagnosing EONS. The authors state to await a 100% sensitive and 100% specific test. In theory, this gold standard is obtained by observing infants while withholding antibiotics, which obviously is unacceptable. Instead combinations of laboratory and clinical signs are used to exclude EONS. Understandably, these tests must have hi...

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  We read with interest the review by AR Bedford Russell and F Kumar[1] about challenges in diagnosing EONS. The authors state to await a 100% sensitive and 100% specific test. In theory, this gold standard is obtained by observing infants while withholding antibiotics, which obviously is unacceptable. Instead combinations of laboratory and clinical signs are used to exclude EONS. Understandably, these tests must have high sensitivity. High sensitivity in a test with poor test characteristics means by definition poor specificity, resulting in overtreatment and all its associated drawbacks, as described in the review. We are thus waiting for new tests with equal sensitivity but higher specificity. However, problems arise when developing this test. First of all, since the sensitivity of the new test must be close to 100%, and the non-inferiority margin must be small to prove non-inferiority an enormous sample size is needed. Secondly, the sample size needed cannot be calculated due to the lack of a gold standard. The same holds true for the numbers needed to treat (NNT), sensitivity and specificity. For these numbers, the incidence or prevalence of EONS in the population is needed. Finally, it is unclear to what extent shortening of the course of antibiotics would be of benefit, and thus the advantage of a more specific test would be unclear. In the context of all these considerations it is remarkable that in the past neonatal antibiotic treatment has been shortened without scientific sound underpinning. So it seems that the only way to move forward is to just shorten treatment and monitor closely, and accept that strong scientific foundation for optimizing EONS treatment will never be obtained before changing the policy.

  Reference list 1 A R Bedford Russell, R Kumar. Early onset neonatal sepsis: diagnostic dilemmas and practical management. Arch Dis Child Fetal Neonatal Ed 2015;100:F350-F354.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  Re: I know you don't like our American brand of English, but......

  • Alison Bedford Russell, Dr
  • Other Contributors:
    • Rohit Kumar

  We thank Dr Perlin for his response which specifically refers to the prevention of early onset Group B streptococcus (GBS) infection.

  Similar declines in GBS EONS have been seen in many other countries that have introduced screening for GBS and IAP. In contrast, in the UK the RCOG recommendation for a risk based approach has not been associated with a fall in the incidence of GBS EONS. If the incidence fell by 75%,...

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  We thank Dr Perlin for his response which specifically refers to the prevention of early onset Group B streptococcus (GBS) infection.

  Similar declines in GBS EONS have been seen in many other countries that have introduced screening for GBS and IAP. In contrast, in the UK the RCOG recommendation for a risk based approach has not been associated with a fall in the incidence of GBS EONS. If the incidence fell by 75%, as would be predicted from the experience of other countries, this would reduce GBS infection in at least 300 babies per year in the UK.

  The UK National Screening Committee do not recommend universal screening for GBS for a number of reasons including that it is not cost effective. However Colbourn et al (BMJ. 2007;335:655) concluded from a detailed analysis that "culture testing for low risk term women, while treating all preterm and high risk term women, would be the most cost effective option". Kaambwa et al (BJOG. 2010;117:1616) concluded that "The current strategy of risk-factor-based screening is not cost-effective compared with screening based on culture". The best test for GBS is enhanced culture medium (ECM) testing of low vaginal and rectal swabs at an estimated cost of ?11, but is not routinely available in the UK. Conventional tests may miss GBS even if it is present.

  Concerns have been expressed about penicillin allergy but true anaphylaxis is rare. Law et al reported (J Med Screen 2005;12:60) that there were no recorded deaths in the first 1.8 million women given IAP in the USA, and other reports have stressed that giving IAP under direct supervision is very safe. Concern has been expressed about the practice of giving women (and therefore their fetuses) large doses of broad spectrum antibiotic before skin incision for caesarean section, as currently recommended by the RCOG, in terms of the effect it might have on the development of the newborn's immune system. Around 33% of pregnant women currently receive antibiotics at some stage during pregnancy, including erythromycin for which there is now evidence of harm, yet the RCOG continue to recommend its use for women with preterm, pre-labour rupture of membranes (Meeraus et al, PLOS ONE | DOI:10.1371/journal.pone.0122034 March 25, 2015.) In contrast, penicillin is narrow spectrum, GBS has never developed resistance to it, and there is no evidence that preventing GBS EONS encourages other organisms to invade. The widespread use of penicillin for over 60 years means that any organisms able to become resistant to it will likely already have done so.

  Current RCOG guidelines recommend giving IAP if a woman is found by chance to be a GBS carrier, yet is managed as if negative for GBS if no swab has been obtained. Her baby Is also managed differently if she is known to be GBS positive. This is illogical and women who have knowledge of GBS have very clearly stated that they wish to be screened for GBS. On the grounds of equity and choice, pregnant women at 35-37 weeks should be offered an equal opportunity to determine their GBS status and protect their babies, which can only be done by screening.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 22 March 2016

  I know you don't like our American brand of English, but......

  • Barry M Perlin, Neonatologist

  Dear Sir:

  I have read the most excellent review of early onset neonatal sepsis (EONS) published recently in these Archives by Dr's Bedford Russell and Kumar. We, in America, have witnessed the gradual evolution from a risk factor approach initially advocated by the American College of Obstetricians and Gynecologists, (as opposed to universal screening during gestation, as recommended by the American Academy of P...

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  Dear Sir:

  I have read the most excellent review of early onset neonatal sepsis (EONS) published recently in these Archives by Dr's Bedford Russell and Kumar. We, in America, have witnessed the gradual evolution from a risk factor approach initially advocated by the American College of Obstetricians and Gynecologists, (as opposed to universal screening during gestation, as recommended by the American Academy of Pediatrics), to universal screening proposed by both organizations. This concordance of governing opinions was reached after data collection by the Centers for Disease Control determined a lower attack rate of EONS via the universal screening method as opposed to the risk factor approach. Dr's Bedford Russell and Kumar have identified this welcome reduction in the USA as well as the controversial nature of a continued risk factor approach in the UK.

  I hope the Royal College of Obstetricians and the UK National Screening Committee come to soon support the relevant change in practice.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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