The Clinical Report is important and timely in attempting to limit antibiotic use to those patients most likely to benefit from them, but I am concerned that the implications of the statement may leave some patients undertreated.

I am most concerned with discontinuing antibiotics in high-risk, ill patients who may have received antibiotics trans-placentally and whose blood cultures show no growth. The authors attempt to justify this by showing time to positive blood cultures are no different in infants whose mothers did versus did not receive antibiotics. This negates the concept of bacterial killing time after exposure to antibiotics, which for Group B Streptococcus, is ∼4–6 hours.1  I am concerned about possible partial treatment of true bacterial infections with early termination of antibiotics.

Neonatal clinicians frequently manage patients exposed to maternal antibiotics for hours, and this conceivably will inhibit bacterial growth. According to the report, with a positive blood culture, clinicians should use Red Book guidelines to determine length of therapy (for instance with Group B Streptococcus, 10–14 days depending on the CSF result). In circumstances where antibiotics MAY HAVE inhibited bacterial growth in the blood culture, surely stopping antibiotics at 36–48 hours is not advised. It would be as if a positive blood culture was followed after 24 hours of antibiotic therapy with a repeat culture that is negative, and antibiotics are stopped after a 2–3 day treatment. That negative culture should give the clinician confidence that they chose the correct antibiotic, but not that a sufficient antibiotic course has been delivered.

In addition, clinicians need to remember that blood is only 1 organ, and other organs may be infected without the blood being inoculated. In the autopsy review of neonatal deaths by Barton et al,2  infection was not diagnosed clinically 61% of the time with deaths in these cases attributed to RDS or immaturity, many of whom were not treated with antibiotics.

Finding no growth in the blood culture at 36–48 hours after multiple hours of in utero antibiotic exposure may be reassuring when no other markers of infection are present, and this is where the use of inflammatory markers such as CRP can be helpful. Although the clinical report mentions other conditions that may be associated with elevations of the CRP, such as asphyxia and pneumothorax (not referenced), certainly an inflammatory response from infection remains the overwhelming etiology of an elevation. In the face of significant risk for neonatal infection, like PPROM and chorioamnionitis, in a mother who received antibiotics prior to delivery AND the infant has elevation of the non-specific inflammatory markers, it not only seems reasonable but also prudent to consider that the CRP or procalcitonin is elevated due to infection. In addition, as shown by Benitz,3  serial normal CRP values have a 99% negative predictive value of serious infection at 48 hrs and should give confidence to discontinue antibiotics. This approach should meet the goal of limiting antibiotics to those most likely infected while minimizing exposure to those not infected.

1
Swingle
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Barton
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Competing Interests

CONFLICT OF INTEREST: The author has indicated he has no potential conflicts of interest to disclose.