Antibiotic-impregnated central venous catheters in the neonatal intensive care unit—PREVAILing questions
Authors: Ameneh Khatami, David Isaacs
Journal: The Lancet Child & Adolescent Health (2019)

Despite being of far-reaching health and economic importance, neonatal intensive care is under-researched globally. Neonatal bloodstream infections are associated with high mortality and substantial morbidity, including neurodevelopmental sequelae, particularly in preterm infants.1Piening BC Geffers C Gastmeier P Schwab F Pathogen-specific mortality in very low birth weight infants with primary bloodstream infection.PloS One. 2017; 12: e0180134Crossref PubMed Scopus (31) Google Scholar Yet, the use of broad-spectrum antibiotics to treat suspected and proven bloodstream infections might also contribute to the growing problem of antimicrobial resistance at a community level,2de Man P Verhoeven BA Verbrugh HA Vos MC van den Anker JN An antibiotic policy to prevent emergence of resistant bacilli.Lancet. 2000; 355: 973-978Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar as well as having substantial effects on the microbiota at an individual level,3Greenwood C Morrow AL Lagomarcino AJ et al.Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter.J Pediatr. 2014; 165: 23-29Summary Full Text Full Text PDF PubMed Scopus (231) Google Scholar which might lead to a range of immediate and long-term health effects.4Langdon A Crook N Dantas G The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.Genome Med. 2016; 8: 39Crossref PubMed Scopus (507) Google Scholar As such, increasing the evidence base for reducing bloodstream infections in this vulnerable population is important, and well conducted studies, even with negative findings, are noteworthy. In The Lancet Child & Adolescent Health, Ruth Gilbert and colleagues5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar report results of the PREVAIL study, a randomised controlled trial done at 18 UK neonatal intensive care units. They found that miconazole and rifampicin-impregnated central venous catheters (CVCs) did not reduce the incidence of bloodstream infections compared with standard CVCs. By contrast, another randomised controlled trial, the CATCH study,6Gilbert RE Mok Q Dwan K et al.Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.Lancet. 2016; 387: 1732-1742Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar found that rifampicin and minocycline-impregnated CVCs reduced the risk of bloodstream infection in older children (age <16 years) by 57% compared with standard CVCs. A possible explanation for the difference in outcomes between neonates and older children is that the wrong antimicrobials were used in the neonatal trial. Rifampicin and minocycline-impregnated CVCs, which reduce CVC-related bloodstream infection incidence in children and adults,7Wang H Huang T Jing J et al.Effectiveness of different central venous catheters for catheter-related infections: a network meta-analysis.J Hosp Infect. 2010; 76: 1-11Summary Full Text Full Text PDF PubMed Scopus (58) Google Scholar are not licensed for use in neonates. Candidaemia is rare, and this study was not powered to detect a difference in the rate of fungal bloodstream infection via miconazole impregnation.5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar As rifampicin resistance can emerge rapidly when this drug is used alone, it is usually preferable to use rifampicin in combination with another antibiotic. Minocycline might protect against the development of rifampicin resistance, although incomplete laboratory data from both randomised controlled trials prevented analysis of the risk of emerging rifampicin resistance with either type of catheter.5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar, 6Gilbert RE Mok Q Dwan K et al.Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.Lancet. 2016; 387: 1732-1742Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar In the PREVAIL study,5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar 35 (78%) of 45 bloodstream infections from blood or cerebrospinal fluid samples were coagulase-negative staphylococci in infants with standard CVCs, compared with 31 (63%) of 49 isolates from infants with antibiotic-impregnated CVCs. The numbers for Gram-negative bacteria were six (13%) of 45 in infants with standard CVCs and ten (20%) of 49 in infants with antibiotic-impregnated CVCs. Although these differences were not statistically significant with such small numbers, infections with Gram-negative bacteria have far greater morbidity and mortality than do infections with coagulase-negative staphylococci, and the potential for antibiotic-impregnated CVCs to select for Gram-negative infections should not be ignored. Clearly, further trials in this area are needed to assess a range of antimicrobial-impregnated CVCs in neonates, with rigorous collection of laboratory data to enable a more complete analysis of the risks. As with any intervention, the number needed to treat for a positive outcome might be reduced by selecting the appropriate patient population, which will also reduce the risk of harm from the intervention. In this case, identification of neonates at the highest risk of bloodstream infection could decrease unnecessary exposure to antibiotics from the antibiotic-impregnated CVC, as well as reducing the cost. In the CATCH trial,6Gilbert RE Mok Q Dwan K et al.Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.Lancet. 2016; 387: 1732-1742Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar the median duration of CVC insertion was relatively short (around 4 days in each group, IQR 2–7), with the median time to bloodstream infection ranging from 4 days to 7·5 days. By contrast, the median duration of CVC insertion in the PREVAIL trial was around 8 days (IQR 5–13).5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar The primary outcome of median time to first bloodstream infection was not reported because of the small number of events, even though around 10% of infants in each study group had a bloodstream infection, a greater proportion than in the CATCH trial.6Gilbert RE Mok Q Dwan K et al.Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.Lancet. 2016; 387: 1732-1742Summary Full Text Full Text PDF PubMed Scopus (69) Google Scholar Thus, the question remains whether in a neonatal population antibiotic-impregnated CVCs might be more useful when a longer duration of CVC insertion is expected. As Gilbert and colleagues point out,5Gilbert 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; (published online April 27.)http://dx.doi.org/10.1016/S2352-4642(19)30114-2PubMed Scopus (26) Google Scholar other infection prevention strategies in intensive care units have substantially reduced the rate of CVC-related bloodstream infection in adults8Pronovost P Needham D Berenholtz S et al.An intervention to decrease catheter-related bloodstream infections in the ICU.N Engl J Med. 2006; 355: 2725-2732Crossref PubMed Scopus (3149) Google Scholar and children, including neonates.9Payne V Hall M Prieto J Johnson M Care bundles to reduce central line-associated bloodstream infections in the neonatal unit: a systematic review and meta-analysis.Arch Dis Child Fetal Neonatal Ed. 2018; 103: F422-F429Crossref PubMed Scopus (52) Google Scholar It is often unclear what proportion of an improvement is attributable to each element of these care bundles and, as such, a single intervention such as antibiotic impregnation of CVCs might have too small an effect to be demonstrable. This should be a call to clinicians and researchers to develop novel and integrated strategies to prevent bloodstream and other infections in neonates and other vulnerable populations. We declare no competing interests. Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trialWe found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection. Full-Text PDF Open Access