The Relationship between Gram-Negative Colonisation and Bloodstream Infections in Neonates: A Systematic Review and Meta-Analysis.

OBJECTIVES: Neonates admitted to Neonatal Intensive Care Units (NICU) are at significant risk of developing bloodstream infections (BSIs). Gram-negative bacteria (GNB) both colonise and infect, but the association between these entities is unclear. By conducting a systematic literature review, we aimed to explore the impact of factors on the association between GN colonisation and GN-BSI at both baby level and unit level. METHODS: We searched Medline, Embase, and Cochrane Library. Observational cohort studies published after 2000 up to June 2016 reporting data on the total number of neonates (0-28 days) colonised with GNB assessed by rectal/skin swab culture and the total number of neonates with GN-BSI (same bacteria) were included. Studies were excluded if data on skin/rectal colonisation, neonates, and GNB could not been identified separately. The meta-analyses along with multivariate meta-regression with random-effect model were performed to investigate factors associated with the GN colonisation and GN-BSI at baby-level and unit-level. RESULTS: 27 studies fulfilled our inclusion criteria, 15 for the baby-level and 12 for the unit-level analysis. Study heterogeneity was high, with suboptimal overall quality of reporting assessed by the STROBE-NI statement (44.8% of items adequately reported). In 1,984 colonised neonates, 157 (7.9%) developed GN-BSI compared with 85 of 3,583 (2.4%) non-colonised neonates. Considerable heterogeneity across studies was observed. Four factors were included in the meta-regression model: Gross domestic product (GDP), pathogen, outbreak, and frequency of screening. There was no statistically significant impact of these factors on GN colonisation and GN-BSI in baby level. We were unable to perform the multivariate meta-regression due to the insufficient reported data for unit level. CONCLUSIONS: Study limitations include the small number and the high heterogeneity of the included studies. While this report shows a correlation between colonisation and BSI risk, this data currently doesn't support routinely screening for GNB. The analysis of large cohorts of colonised neonates with clinical outcomes is still needed to define the major determinants leading from colonisation to infection