Risk factors for late onset gram-negative infections: a case–control study

Late onset infections represent a major problem in neonatal units, as they affect approximately 25% of very low birth weight (VLBW) infants. In particular, late onset gram-negative sepsis (LOGNS) and meningitis represent a significant cause of morbidity and mortality in newborns. Surveillance data collected over the last two decades disclose the increasing contribution of gram-negative organisms to late onset sepsis, with a more than twofold increase from 18% (1986–1994) to 43% (1996–2000). The mortality of LOGNS is also high and an inverse relationship with gestational age and birth weight has been well described.
Several studies have investigated the potential risk factors for late onset neonatal infections, including aspects of both maternal and neonatal care. Many of these factors, however, are common among premature babies, making it difficult to draw definite conclusions regarding causality.
On this basis, an English group has conducted a retrospective case-control study in a tertiary neonatal unit in London in order to identify potential risk factors for cases of LOGNS and to review the incidence, epidemiology and mortality of LOGNS.
Consecutive inborn infants with late onset (>48 h of life) invasive gram-negative infections diagnosed between 1999 and 2005 were included in this analysis. A total of 73 cases of LOGNS were identified. Controls were healthy infants matched for gestation and time of admission to the neonatal unit. The main outcome measures were clinical and risk factor data.
The overall incidence of LOGNS was 1.85/1000 live births; it occurred in 2.2% of total admissions and 4.4% of inborn VLBW admissions. Enterobacter spp. (28%), Escherichia coli (27%) and Klebsiella spp. (21%) were the most common pathogens. Overall, case death was 27% in cases versus 13.5% in controls, although a statistical difference was not reached. Similarly, no significant difference between cases and controls regarding maternal risk factors was reported. Mechanical ventilation, total parenteral nutrition (TPN) and its duration, presence of a central venous line and its duration, use of specific antibiotics and the occurrence of necrotising enterocolitis at or before the first positive culture were all significantly associated with case status in univariate analysis. However, in a multivariate logistic regression analysis accounting for influence of gestational age, only duration of TPN at or before first positive blood culture remained independently associated with LOGNS (p<0.001).
In conclusion, this study suggests that LOGNS predominantly occurs in premature and VLBW babies. Maternal factors do not appear to be associated with LOGNS and although a number of significant associations with neonatal factors were identified on univariate analysis, many of these likely reflect their prevalence among premature infants. Only the duration of TPN appears to be an important risk factor for LOGNS, in line with previous findings. The mechanisms underlying this association require further investigations.

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