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Outcomes of Children With Enterobacteriaceae Bacteremia With Reduced Susceptibility to Ceftriaxone: Do the Revised Breakpoints Translate to Improved Patient Outcomes?

Tamma, Pranita D. MD, MHS*; Wu, Harold BA*; Gerber, Jeffrey S. MD, PhD; Hsu, Alice J. PharmD, BCPS, AQ-ID; Tekle, Tsigereda MT, ASCP§; Carroll, Karen C. MD§; Cosgrove, Sara E. MD, MS

The Pediatric Infectious Disease Journal: September 2013 - Volume 32 - Issue 9 - p 965–969
doi: 10.1097/INF.0b013e31829043b3
Antimicrobial Reviews

Background: In 2010, the Clinical and Laboratory Standards Institute (CLSI) revised and lowered the ceftriaxone minimum inhibitory concentration breakpoints for Enterobacteriaceae and removed the requisite extended spectrum β-lactamase phenotypic testing for organisms with elevated minimum inhibitory concentrations. The impact that these recommendations have on clinical outcomes of children have not been previously evaluated.

Methods: We conducted a retrospective study to compare clinical outcomes between children treated with ceftriaxone and those treated with broader spectrum β-lactams for Enterobacteriaceae bacteremia with reduced susceptibility (minimum inhibitory concentrations 4–8 µg/mL) to ceftriaxone according to the new CLSI interpretive criteria. Mortality and microbiological relapse were evaluated using a multivariable logistic regression model.

Results: There were a total of 783 unique children with Enterobacteriaceae bacteremia during the study period. Using the CLSI breakpoints before 2010, 76 children would have had clinical isolates resistant to ceftriaxone. With the revised breakpoints, 229 Enterobacteriaceae isolates would no longer be susceptible to ceftriaxone (>300% increase). Of the 136 children who met eligibility criteria, 63 children received ceftriaxone and 73 children received broader spectrum β-lactams. There was no difference in 30-day mortality (odds ratio 0.81, 95% confidence interval: 0.31–2.59) or microbiological relapse (odds ratio 0.97, 95% confidence interval: 0.36–2.66) between the groups.

Conclusions: Our findings do not support the proposed clinical benefit of more conservative CLSI breakpoints. The revised breakpoints promote increased broad-spectrum β-lactam use. The need for lowered ceftriaxone breakpoints against Enterobacteriaceae in children needs to be reevaluated in larger prospective studies.

From the *Department of Pediatrics, Johns Hopkins Medical Institutions, Division of Pediatric Infectious Diseases, Baltimore, MD; Department of Pediatrics, The Children’s Hospital of Philadelphia, Division of Infectious Diseases, Philadelphia, PA; Department of Pharmacy, Johns Hopkins Medical Institutions, Baltimore, MD; §Department of Pathology, Johns Hopkins Medical Institutions, Division of Medical Microbiology, Baltimore, MD; and Department of Medicine, Johns Hopkins Medical Institutions, Division of Infectious Diseases, Baltimore, MD.

Accepted for publication March 04, 2013.

This work was supported by Thrasher Research Fund Early Career Award and the Clinician Scientist Award (P.D.T.). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Pranita D. Tamma, MD, MHS, Johns Hopkins Medical Institutions, Division of Pediatric Infectious Diseases, Department of Pediatrics, 200 North Wolfe Street, Suite 3155, Baltimore, MD. E-mail:

© 2013 by Lippincott Williams & Wilkins, Inc.