Where does sepsis come from?

One of the findings of the recent SIFT trial was that although the babies in the fast feeding group had shorter duration of parenteral nutrition, TPN, (and presumably of central lines), they did not have less late-onset sepsis, LOS. Why not?

The difference in duration of TPN was only 2 days (median 9 days with fast feeding, 11 days with slow) which maybe didn’t give enough power to show a difference in LOS. But both culture positive sepsis and clinically suspected sepsis were almost identical in the 2 groups.

In the CNN 2017 report, LOS incidence for infants up to and including 32 weeks gestation varied between about 1.7 and 5 infections per 1000 patient days, central-line associated blood stream infections, CLABSI, varied between 1.9 and 12 per 1000 central line days. So a much greater variation in CLABSI than in LOS overall. 75% of CoNS infections were CLABSI, compared to about 64% of nonCoNS infections, in other words the bacteriologic profile of CLABSI differs from infections when no line is present, but many “CLABSI” are caused by enteric gram negative organisms.

In the recently available 2018 CNN report if you look at the 2 figures for comparisons of LOS and for CLABSI between centers, you can see that the site with the highest CLABSI rates did not have a very high rate for overall LOS, in fact they were exactly on the line for an average rate for overall LOS, whereas the site with the highest LOS rate at 6.9 per 1000 patient days had a lower than average rate of CLABSI (4.7 per 1000 catheter days, compared to 6.6 for the network as a whole).

Our quality control initiatives for reducing LOS have been multi-pronged, but have included a strong movement to try and reduce CLABSI, we, in my hospital, now take out central lines when enteral feeding is established at more than 120 mL/kg/d, for example, which leads to a short period with less nutrition. But, in fact, as mentioned most organisms causing late-onset sepsis, other than CoNS, are enteric bacteria, and they can usually be found in the individual baby’s GI tract prior to that baby developing an infection.

There are many studies supporting this finding, here are a couple of recent examples and a review article.

Stewart CJ, et al. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017;5(1):75.

Taft DH, et al. Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants. PloS One. 2015;10(6):e0130604.

Masi AC, Stewart CJ. The role of the preterm intestinal microbiome in sepsis and necrotising enterocolitis. Early Hum Dev. 2019;138:104854.

Our emphasis on central lines as a risk for sepsis is partly misplaced I think. If I reduce CLABSI (by taking out central lines faster, for example) but don’t impact LOS, then I haven’t benefitted the babies at all. Especially if the rate of LOS goes up, because of skin disruption from multiple IV attempts, or because people are less careful about handwashing when the baby no longer has a central line, or (make up your own potential explanation and insert here).

I am not suggesting we back down on efforts to reduce central line infections; scrupulous attention to aseptic technique when handling a central line, full asepsis during insertion, enormous care around dressing cleanliness and maintenance, and so on are essential. But preventing translocation of intestinal bacteria, the real culprits in LOS, is going to give more benefit in terms of LOS.

How to do that? Infants with strong colonization of their GI tract with bifidobacteria and other probiotic organisms are at lower risk. And although there is some evidence that probiotic supplementation decreases LOS, the impact seems limited at present. Enhancing the efficacy of probiotics, by the addition of appropriate prebiotics, in particular the human milk oligosaccharides such as  2′-fucosyllactose, which feeds bifidobacteria, and is found in human milk, might really help to normalise gut colonization, which displaces pathogens and may reduce LOS.


About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , , , . Bookmark the permalink.

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