PREVenting infection using Antibiotic Impregnated Long lines (PREVAIL)

OVERALL AIM: To determine whether antimicrobial and antifungal impregnated peripherally inserted central venous catheters (AM-PICC) should be introduced across the NHS for very preterm babies. I) RANDOMISED CONTROLLED TRIAL PRIMARY RESEARCH QUESTION: In very preterm babies who require a peripherally inserted central venous catheter (PICC), does antimicrobial and antifungal impregnation of the PICC reduce the time to blood stream infection (BSI)? DESIGN AND SETTING: The study will be a pragmatic, unblinded, 2-arm randomised controlled trial to determine the effectiveness, resource use and cost of antimicrobial (rifampicin) and antifungal (miconazole) impregnated PICC (AM-PICC) compared with standard PICC (S-PICC) for reducing BSI. The setting will be neonatal intensive care units (NICU). TARGET POPULATION: New-born babies who require the narrowest PICC (Premicath 1 French gauge). Premicaths are designed for babies <1kg and almost all participants will be very preterm (<32 weeks of gestation). TECHNOLOGY: Systematic reviews of different types of line impregnation report that antimicrobial-impregnation is one of the most effective options for preventing BSI [1]. No published trials of antimicrobial impregnation have included children and a recently completed trial in paediatric intensive care (CATCH – trial number 08/13/47) is confined to larger minocycline-rifampicin catheters (French gauge 4/5) suitable for larger children. A further trial is needed in preterm babies because the magnitude and mechanism of effect and outcomes differ from previously studied patient groups. First, NICUs have one of the highest rates of BSI of any patient group because preterm babies have immature immunity and skin defences which allow normally benign skin organisms to track internally and externally along the catheter from the insertion site [2]. Second, parenteral nutrition infused in a substantial proportion of babies with PICC increases organism adherence and the development of BSI [3, 4]. Third, the lumens of the lines are far narrower (1 Fr compared with 4/5 Fr in children in CATCH), which may affect bacterial adherence and reduce potential benefits of impregnation. Fourth, the combination of rifampicin and an antifungal – miconazole - has not previously been evaluated in any comparable patient group on in children for efficacy against BSI or emergence of resistant organisms [5, 6]. The occurrence of BSI in very preterm babies is associated with a higher mortality than in more mature children and survivors are at increased risk of long-term neurological impairment, even when BSI is due to skin organisms [7]. We will compare AM-PICC compared with S-PICC (both polyurethane and manufactured by Vygon). Despite availability of a fully licensed AM-PICC, no NICUs in the UK are using this product. This appears to be because of the lack of evidence for benefits in preterm neonates, concerns about antimicrobial resistance, and the additional costs of impregnated PICC. The S-PICC (Premicath) is the most widely used PICC in UK NICUs. Blinding is not possible because brown staining of AM-PICC due to rifampicin cannot be obscured during insertion or whilst in situ. PRIMARY OUTCOMES: Time to BSI based on positive blood culture (including fungal BSI) taken between 24 hours after PICC insertion until 48 hours after removal [8]. A sensitivity analyses for severity will only include positive cultures for skin organisms (e.g. coagulase staphylococci - CONS) if the baby is treated for more than 72 hours with intravenous antimicrobials or dies during treatment. Blood cultures will be taken when clinically indicated according to standard practice. No additional blood will be required. SECONDARY OUTCOMES: Rifampicin resistance in isolates from blood cultures or PICC tips; rate of death before discharge; measures of BSI (rate per 1000 PICC-days, proportion of babies with 1 or more BSI, rate of catheter-related BSI), blood culture fre