Central venous catheters (CVCs) impregnated with antimicrobial agents are no better than standard CVCs for avoiding bloodstream infection in pre-term babies.
This NIHR-funded trial compared peripherally inserted CVCs that had been impregnated with a combination of the antifungal miconazole and the broad-spectrum antibiotic rifampicin, against standard non-antimicrobial-impregnated CVCs for preterm babies in intensive care. Rates of bloodstream infections were similar in both groups, and no differences in other clinical outcomes were found.
Researchers reported no evidence of clinical benefit or harm from the antimicrobial-impregnated CVCs. They noted these antimicrobial-impregnated CVCs are rarely used in the UK and are more expensive than standard alternatives.
Why was this study needed?
Around 70% of pre-term babies born before 32 weeks of gestation need CVCs for nutrition, fluids, and medications. Bloodstream infection is the most common serious complication arising from their use and can be fatal. Infection is more common in very pre-term babies, with rates of up to 30%.
Previous small trials have suggested that adults and children may benefit from antimicrobial-impregnated CVCs, and national guidelines reflect this. However, a 2015 Cochrane review noted insufficient evidence to recommend use in newborn babies and called for a large randomised controlled trial. This study examined whether antimicrobial impregnated CVCs provided enough benefit to neonatal intensive care patients to recommend their use.
What did this study do?
PREVAIL, a randomised controlled trial, took place in 18 neonatal intensive care units around the UK. Newborn babies who required a CVC for any purpose were eligible for the trial. Researchers randomly assigned 861 babies (88% born before 32 weeks) to receive either miconazole and rifampicin-impregnated CVCs or standard CVCs.
Researchers assessed bloodstream or cerebrospinal fluid infection by microbiological testing where clinically indicated. Results were analysed on an intention-to-treat basis.
The study was designed to detect a 50% reduction in bloodstream infections, based on previous trials in adults and children. Clinicians were not blinded as rifampicin causes brown staining of CVCs.
What did it find?
- The time from allocation to first bloodstream infection was similar in each group (hazard ratio 1.11, 95% confidence interval (CI) 0.73 to 1.67); approximately 10-11% of babies in each group developed a bloodstream infection.
- The rates of bloodstream infection per 1,000 days with a CVC were similar in each group at 13.15 per 1,000 days with an antimicrobial-impregnated CVC and 10.87 with a standard CVC (hazard ratio 1.21, 95% CI 0.78 to 1.88).
- There were no differences in clinical outcomes between the groups when measured at discharge, or in deaths within six months of treatment allocation.
- There was no evidence of a difference in treatment effect for babies born before 28 week’s gestation compared with those of 28 weeks or more.
- The median time to removal of the CVC was similar in each group, at about 8 days.
What does current guidance say on this issue?
The 2014 epic3 guidelines for preventing healthcare-associated infections in NHS hospitals in England include detailed advice on insertion, care and maintenance of CVCs. They provide general principles but do not consider care of babies less than one year old. The guidelines recommend the use of antimicrobial-impregnated CVCs in adults under specific circumstances.
The 2018 revision of the British Association of Perinatal Medicine guidelines on the use of CVCs in neonates does not mention antimicrobial-impregnated CVCs.
What are the implications?
The trial does not support the use of antimicrobial-impregnated CVCs to prevent bloodstream infection for babies in neonatal intensive care.
The authors note that sick pre-term babies are at risk of infection from multiple sources due to invasive procedures and devices, high gut permeability, and immature immune systems. Many of the infections seen in this study may not have been directly related to the CVC, and research is required into alternative approaches for preventing infection.
A linked editorial asks whether CVCs impregnated with other antimicrobials should now be tested. However, they note that a single intervention, such as antimicrobial impregnation of CVCs, may not demonstrate significant benefit now that infection control strategies in intensive care units have already greatly reduced infection rates.
Citation and Funding
Gilbert R, Brown M, Rainford N 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;3(6):381-90.
The study was funded by the NIHR Health Technology Assessment programme (project number 12/167/02).
British Association of Perinatal Medicine. Use of central venous catheters in neonates: a framework for practice. London: British Association of Perinatal Medicine; revised 2018.
Khatami A and Isaacs D. Antibiotic-impregnated central venous catheters in the neonatal intensive care unit—PREVAILing questions. Lancet Child Adolesc Health. 2019;3(6):366-7.
Loveday HP, Wilson J, Pratt RJ et al. epic3: national evidence-based guidelines for preventing healthcare-associated infections in NHS hospitals in England. J Hosp Infect. 2014;86(suppl 1):S1-70.
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