In older children and adults who need central venous access, using catheters impregnated with stuff that kills bugs decreases invasive sepsis rates. A multicentre trial in English PICUs showed a reduction in sepsis from 4% to 1% when antibiotic impregnated catheters were used. In that study only a minority of the culture-positive sepsis was for coagulase negative staph (CoNS); given the differences in bacteriology, immune function, microbiome, and frequency of prolonged central line use, compared to older children, an RCT in the NICU was essential.
The PREVAIL trial was a multicentre RCT in 18 English NICUs, (Gilbert R, et al. Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial. Lancet Child Adolesc Health. 2019) newborn infants in the NICU who needed a peripherally inserted central catheter (picc) were randomized to either a regular 1Fr catheter or a catheter impregnated with rifampicin and miconazole. Allocation was masked, but the catheters were easily distinguished as the antibiotic ones were brown, therefore the intervention was unmasked.
The primary outcome was time to first bacterial infection, bloodstream or meningeal. I’m not sure why this was chosen as the primary outcome, the risk being that the catheters might delay the onset of infection by a couple of days, but not the overall incidence of infection. To me the clinically important question would be whether the total number of infections is reduced by using the special catheters, not how long it takes to get infected. I presume that this outcome was chosen to take account of the differing duration of catheter use.
In any case, the trial showed nothing.
Which is, in fact, not true. They showed the very important outcome that there was no appreciable difference in infection frequency between groups, no matter how they were analysed.
The same proportion of infants had infections during catheter placement, and the time to first infection was identical. About 11% in each group had an infection, there were actually slightly more babies in the antibiotic impregnated group with an infection than controls.
Infections per 1000 catheter days were also similar, and slightly higher in the antibiotic impregnated group (13 vs 11).
My main comment about this study is:
This is exactly the kind of study that we need to do in neonatology. A simple clinical question, with a clear, clinically important, outcome, a simple irreprochable research design, performed rapidly with immediate open-access publication. Let’s have more of this!
You could ask why this might be so different to older children, part of the reason might be the different bacteriology, 2/3 of the infections in this study were CoNS, 66 of a total of 94 organisms were CoNS, compared to a minority in older children.
Also I think the importance of CLABSI, (Catheter-Linked Acute Blood Stream Infections) as they are now called, has been overstated in the NICU. It is the overall frequency of late-onset sepsis which is important, some units have been very succesful at reducing CLABSI, but without much impact on overall LOS (Late-Onset Sepsis) rates. Many nosocomial sepsis events in the preterm are with gram negative, intestinal organisms, CoNS sepsis rates are inflated by contaminated cultures, and are much less important for long term outcomes.
Before this study we could all have been (mis)-led into using antibiotiic impregnated catheters in the newborn. This is exactly why RCTs PREVAIL.