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Empiric Monotherapy Versus Combination Therapy for Enterobacteriaceae Bacteremia in Children

Berkowitz, Nina M. MPH*; Spaeder, Michael C. MD, MS; DeBiasi, Roberta L. MD, MS‡,§,¶; Campos, Joseph PhD§,¶,**; Singh, Nalini MD, MPH*,‡,§

The Pediatric Infectious Disease Journal: November 2015 - Volume 34 - Issue 11 - p 1203–1206
doi: 10.1097/INF.0000000000000885
Original Studies

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.

From 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.

Accepted for publication June 18, 2015.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Nalini Singh, MD, MPH, Department of Epidemiology, The George Washington University, Children’s National Medical Center, 111 Michigan Avenue, Northwest, Washington, DC 20010. E-mail:

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