Minimum Duration of Antibiotic Treatment Based on Blood Culture in Rule Out Neonatal Sepsis

Background: Neonatologists usually wait 48 hours for blood culture results before deciding to discontinue antibiotics. The objective of the study was to analyze time to positive blood culture in rule out sepsis and estimate the minimum duration of antibiotics. Methods: Retrospective analysis of blood culture at the Neonatal Intensive Care Unit, McMaster Children's Hospital (January 2004 to December 2013) using BacT/Alert (R) 3D microbial system was conducted. We calculated average time taken for blood culture samples to emit a positive signal and compared it between Gram-positive and Gram-negative organisms. Kaplan-Meier curves for time to detect positive culture were generated. A Cox proportional hazard regression model with the outcome variable time to detect positive blood culture and predictor variables early-onset sepsis (EOS) versus late-onset sepsis (LOS), Gram-positive versus Gram-negative and definite versus possible pathogen versus contaminant was generated. Results: Of 7,480 blood cultures performed in 9,254 neonates, 885 samples grew microorganisms. 845 culture reports from 627 neonates were analyzed. Definite or opportunistic pathogens caused 815 (96%) infections (54 EOS and 791 LOS) and the rest were contaminants. Gram-negative organisms grew significantly faster than Gram-positive (P < 0.001). Cultures from EOS were positive significantly earlier than LOS (P = 0.032). Gram-negative status was an independent predictor of early detection of a positive culture (hazard ratio 3.5 [95% CI, 2.7-4.5] P < 0.001). Conclusion: The probability of positive blood culture beyond 24 hours for a Gram-negative organism is small. Empiric antimicrobial treatment can be reduced after 24 hours to target only Gram-positive organisms in LOS and can be stopped in EOS unless clinical or laboratory parameters strongly suggest sepsis.