Empiric combination therapy for gram-negative bacteremia.

Area of Science:

• Pediatric Infectious Diseases
• Antimicrobial Stewardship
• Clinical Pharmacology

Background:

• Empirical combination antibiotic regimens (β-lactam and aminoglycoside) are common in pediatric Gram-negative bacteremia.
• Limited data exist on the comparative benefits of empirical combination therapy versus monotherapy in pediatric patients with Gram-negative bacteremia.

Purpose of the Study:

• To evaluate the association between empirical combination antibiotic therapy and outcomes in children with Gram-negative bacteremia.
• To compare 10-day mortality and duration of bacteremia between combination therapy and monotherapy groups.

Main Methods:

• Retrospective cohort study of pediatric patients treated for Gram-negative bacteremia (2004-2012).
• 1:1 nearest-neighbor propensity-score matching was used to compare outcomes.
• Analysis included assessment of 10-day mortality and duration of bacteremia.

Main Results:

• Ten-day mortality was similar between combination therapy and monotherapy groups (OR, 0.84; 95% CI, 0.28-1.71).
• Combination therapy did not significantly decrease the duration of bacteremia (-0.51 days; 95% CI, -2.22-1.48).
• A survival benefit was observed for combination therapy in children with multidrug-resistant Gram-negative organisms (OR, 0.70; 95% CI, 0.51-0.84).

Conclusions:

• Routine empirical addition of aminoglycosides to β-lactams offers no clear advantage for pediatric Gram-negative bacteremia.
• Combination therapy may benefit children with risk factors for multidrug-resistant Gram-negative organisms (MDRGN).