Empirical Antibiotic Activity and Outcomes in Pediatric Gram-Negative Bloodstream Infections: A Rank-based Composite
Sophie C H Wen1,2, Melissa J Hardy1, Abdullah T Aslan1,3
1The University of Queensland, Centre for Clinical Research, Brisbane, Australia.
Summary
Timely active empirical therapy (AET) did not improve clinical outcomes in children with gram-negative bloodstream infections (GNBSI). Composite endpoints are valuable for detecting differences in high-income settings where mortality is low.
Area of Science:
- Pediatric Infectious Diseases
- Clinical Microbiology
- Health Services Research
Background:
- Active empirical therapy (AET) is often recommended for bloodstream infections.
- Low pediatric mortality in high-income countries makes mortality alone an insufficient endpoint for AET studies.
- Composite endpoints combining multiple outcomes may better detect treatment effects.
Purpose of the Study:
- To assess the impact of AET on clinical outcomes in hospitalized children with gram-negative bloodstream infections (GNBSI).
Main Methods:
- Prospective surveillance data from Australian children with GNBSI were analyzed.
- A composite endpoint included mortality, time to death, ICU admission, relapse, and hospitalization duration.
- Inverse probability of treatment weighting and generalized pairwise comparison were used for analysis.
Main Results:
- Active empirical therapy (AET) occurred in 597 episodes, inactive empirical therapy (IET) in 62.
- No significant difference in the composite outcome was found between AET and IET (adjusted win ratio 1.04, p=0.83).
- Individual outcome components showed no significant differences between groups.
Conclusions:
- In high-resource settings, AET did not demonstrate improved outcomes for pediatric GNBSI compared to IET.
- The impact of initial antibiotic activity may be less significant than assumed in these settings.
- Effective therapy remains crucial for severe infections and in low-resource environments.
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