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Empiric Monotherapy Versus Combination Therapy for Enterobacteriaceae Bacteremia in Children
Nina M Berkowitz1, Michael C Spaeder, Roberta L DeBiasi
1From the *Department of Epidemiology, School of Public Health, The George Washington University, Washington, DC; †Division of Critical Care Medicine, ‡Division of Infectious Diseases, Children's National Medical Center, Washington, DC; §Department of Pediatrics, ¶Department of Microbiology/Immunology/Tropical Medicine, and **Department of Pathology, School of Medicine, The George Washington University, Washington, DC.
Insights
For pediatric Enterobacteriaceae bacteremia, combination antimicrobial therapy showed no advantage over monotherapy. This finding is crucial for guiding effective treatment strategies in young patients with serious infections.
Area of Science:
- Infectious Diseases
- Pediatric Medicine
- Antimicrobial Stewardship
Background:
- Enterobacteriaceae bacteremia poses a significant life-threatening risk in pediatric patients.
- Prompt and effective antimicrobial therapy is essential for reducing severe illness and fatalities.
Purpose of the Study:
- To compare the efficacy of empiric combination antimicrobial therapy versus monotherapy in children and young adults with Enterobacteriaceae bacteremia.
- To determine if combination therapy offers superior outcomes in terms of time to negative blood cultures.
Main Methods:
- Retrospective cohort study of patients under 21 years old from 2008-2011.
- Defined monotherapy as a beta-lactam agent alone; combination therapy involved a beta-lactam plus an aminoglycoside for at least 48 hours.
- Outcome was measured by response to therapy, specifically time to negative blood culture.
Main Results:
- Klebsiella spp., Escherichia coli, and Enterobacter spp. were the most common causative agents.
- Combination therapy was more frequently used in cancer patients, while monotherapy was more common in those with gastrointestinal disease or on total parenteral nutrition.
- No significant difference in treatment outcomes was observed between monotherapy and combination therapy groups (P = 0.86).
Conclusions:
- Empiric combination therapy with a beta-lactam and aminoglycoside agent is not superior to monotherapy with a beta-lactam agent alone for Enterobacteriaceae bacteremia in pediatric and young adult populations.
- These findings support optimizing antimicrobial strategies to avoid unnecessary combination therapy in this patient group.
Background:
Bacteremia caused by members of the Enterobacteriaceae can be life threatening. Appropriate antimicrobial therapy is critical to reducing morbidity and mortality.
Methods:
This retrospective cohort study (2008-2011) was conducted in children and young adults (<21 years of age) hospitalized with Enterobacteriaceae bacteremia with clinical signs and symptoms of infection. We investigated whether combination empiric antimicrobial therapy was superior to monotherapy for treatment. Monotherapy was defined as empiric therapy with a β-lactam agent alone. Combination therapy was defined as coadministration of a β-lactam agent with an aminoglycoside agent for at least 48 hours before the susceptibility data were known. Outcome was measured as the response to therapy (defined as the time to negative blood culture) and was compared among patients administered monotherapy versus combination therapy.
Results:
Of 203 episodes of Enterobacteriaceae bacteremia, 78 (38%) were caused by Klebsiella spp, 73 (36%) were caused by Escherichia coli, and 52 (26%) were caused by Enterobacter spp. Of 203 episodes of bacteremia caused by 3 organisms of greatest interest, 101 (50%) were treated with combination therapy. Patients with cancer were more likely to receive combination therapy (38% vs. 16%; P < 0.001); patients with gastrointestinal disease and those receiving total parenteral nutrition were more likely to receive monotherapy (58% vs. 39%; P = 0.006 and 54% vs. 37%; P = 0.013, respectively). There was no difference in outcome in patients receiving monotherapy versus combination therapy (P = 0.86).
Conclusion:
Combination therapy consisting of a β-lactam agent and an aminoglycoside agent was not superior to monotherapy with a β-lactam agent alone for managing Enterobacteriaceae bacteremia in children and young adults.
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