I wrote a blog post about 3 years ago about a study examining procalcitonin use in neonatal early-onset sepsis. You can see from my post that the authors didn’t, to my mind, show any utility of procalcitonin (PCT) either alone or in addition to the CRP for diagnosis of EOS. They have just published a secondary analysis of the trial (Stocker M, et al. C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study. Clin Infect Dis. 2020) which shows the following:
Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours
Which is all well and good, but not much use. Blood cultures are almost always positive by 36 hours, so by the time the PCT and CRP are useful you already know if the baby has sepsis or not! The actual time to positive cultures has just been reviewed, (Marks L, et al. Time to positive blood culture in early-onset neonatal sepsis: A retrospective clinical study and review of the literature. J Paediatr Child Health. 2020;56(9):1371-5). Using the Bactec system they found that 98% of positive blood cultures in babies with EOS were positive at less than 24 hours, and the only one that was positive later was taken after antibiotics had been started. In their review of the literature, blood cultures for EOS were positive by 24 hours in 92% to 100%. In my practice, we now stop antibiotics if cultures are negative at 36 hours, the idea being that in the rare case of a culture being positive between 36 and 48 hours we can restart the antibiotics without actually missing a dose, but the dose which would normally have been given at 48 hours is avoided if the cultures are negative. Given this new publication, we can probably stop even earlier, at least for EOS, and limit antibiotic courses to one or two doses for the majority of babies who are screened but do not have EOS.
The Bactec system and other similar systems are extremely sensitive to even very low bacterial counts as long as 1 mL of blood is used, they screen the culture medium continuously and an alarm bell rings in the lab if they become positive, bringing a laboratory technician scurrying over to get the result and phone it to the NICU. I actually don’t know how it all works, but that is the image I have in my mind. We have a very efficient lab that always telephones when a blood culture is positive, but just as a backup we ensure that someone checks with the laboratory directly before stopping antibiotics. Reducing unnecessary antibiotic use is an important goal, this most recent publication again fails to show that CRP or procalctinon measurements, single or repeated, assist in achieving that goal.