Background: Gram-negative bloodstream infections (BSIs) cause 20-30% of late onset sepsis in neonatal intensive care unit (NICU) patients and have mortality rates of 30-50%. We investigated risk factors for late onset Gram-negative sepsis in very low birth weight (<1500 g) NICU patients.

Methods: We performed a case-control study as part of a larger 2-year clinical trial that examined the effects of hand hygiene practices on hospital-acquired infections. In this substudy, a case was a very low birth weight infant with a hospital-acquired Gram-negative BSI; control subjects, matched on study site and hand hygiene product, were chosen randomly from the patients who did not have Gram-negative BSIs. Potential risk factors were analyzed by Mantel-Haenszel methods and conditional logistic regression.

Results: There were 48 cases of Gram-negative BSI. In multivariate analysis, we found that the following variables were significantly associated with Gram-negative BSI: central venous catheterization duration of >10 days; nasal cannula continuous positive airway pressure use; H2 blocker/proton pump inhibitor use; and gastrointestinal tract pathology.

Conclusions: These analyses provide insights into potential strategies to reduce Gram-negative BSIs. Catheters should be removed as possible and H2 blockers/proton pump inhibitors should be used judiciously in NICU patients. The association between nasal cannula continuous positive airway pressure and Gram-negative BSIs requires further investigation. The association of gastrointestinal tract pathology with Gram-negative BSIs identifies a high risk group of neonates who may benefit from enhanced preventative strategies.

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