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Healthcare-associated Staphylococcus aureus Bacteremia in Children: Evidence for Reverse Vancomycin Creep and Impact of Vancomycin Trough Values on Outcome

McNeil, J. Chase MD; Kok, Eric Y. BS; Forbes, Andrea R. RN; Lamberth, Linda MS; Hulten, Kristina G. PhD; Vallejo, Jesus G. MD; Mason, Edward O. PhD; Kaplan, Sheldon L. MD

The Pediatric Infectious Disease Journal: March 2016 - Volume 35 - Issue 3 - p 263–268
doi: 10.1097/INF.0000000000000991
Original Studies

Introduction: Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 μg/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes.

Methods: Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Children's Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine.

Results: Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 μg/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 μg/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 μg/mL. A vancomycin trough >15 μg/mL was, however, an independent risk factor for AKI.

Conclusions: Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

Supplemental Digital Content is available in the text.

From the *Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas; and Infectious Diseases Service, Texas Children’s Hospital, Houston, Texas.

Accepted for publication September 4, 2105.

This study was supported in part by the National Institutes of Health (NIAID K23AI099159 to J.C.M.). The Staphylococcus aureus surveillance study was funded in part by Pfizer (investigator initiated grant to S.L.K.); this sponsor had no role in the conduct of the study or review of data. S.L.K. also receives funding for unrelated investigator initiated studies from Forest Labs and Pfizer. The other authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: J. Chase McNeil, MD, Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, 1102 Bates St. Suite 1150, Houston, TX 77030. E-mail:

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