Expert review of CLABSI prevention in the NICU: supporting the transition of investigational drugs into clinical practice

Abstract

Central venous catheters (CVCs) are essential for administering life-saving medications, parenteral nutrition, and fluids in extremely premature (EP; i.e., 28 weeks' gestational age) infants. Indeed, CVCs have enabled increased survival and improved outcomes in EP infants over the last several decades. However, CVCs remain a major risk factor for central line-associated bloodstream infection (CLABSI), which can lead to serious complications in this vulnerable population. While many neonatal intensive care units (NICUs) have adopted CVC bundles to reduce CLABSI risk, implementation remains inconsistent, contributing to significant variability across centers. A minimized and reproducible baseline rate of CLABSI is important not only to physicians caring for EP infants and their families but also to clinical investigators and regulatory authorities in the evaluation of experimental therapies aimed at combating the complications of prematurity, such as bronchopulmonary dysplasia, retinopathy of prematurity, and impaired neurological development. CLABSIs may confound clinical outcomes and thus impact the interpretation of trial results. We propose a standardized central line bundle, informed by current clinical practice and a critical appraisal of the literature, for mandatory use in clinical trials.

Conclusion: Consistent application of a standardized central line bundle would reduce variability in baseline CLABSI rates across study sites, enabling more accurate benefit-risk assessments of experimental therapies, particularly those requiring central venous access, in this population of infants with a high unmet medical need.

What is known: • Central venous catheters (CVCs) are essential for administering life-saving treatments in extremely premature infants, significantly improving their survival and outcomes. CVCs, however, are known to increase the risk of central line-associated bloodstream infection (CLABSI). • Central line bundles are routinely implemented in clinical practice with demonstrable benefit in reducing CLABSI. Still, their impact often wanes as the focus and stringency on bundle components and audit programs decrease.

What is new: • We propose a standardized central line bundle for mandatory use in clinical trials. This will help reduce variability in baseline CLABSI rates across study centers, enabling a more accurate evaluation of the benefit-risk profile of experimental therapies-especially those requiring administration via central venous catheters.

Keywords: BPD; CLABSI; Central venous catheter; Neonatology; Sepsis.