Nosocomial MRSA Bacteremia in Children: Evidence for “Reverse Vancomycin Creep” and Limited Benefit of Elevated Vancomycin Serum Troughs
Background: Vancomycin is the most commonly used drug for the treatment of severe MRSA infections. Previous studies in adults with nosocomial infection have shown that vancomycin MICs have increased over time and that MIC > 1 µg/ml are associated with adverse outcomes. The IDSA recommends vancomycin goal trough levels 15-20 µg/ml in adults with severe MRSA infections. There are little data on these issues in children.
Methods: Isolates and patients with nosocomial MRSA bacteremia during the years 2003-2013 were identified from a prospective surveillance study. Vancomycin MICs were determined by E-test. Medical records were reviewed; acute kidney injury (AKI) was defined as a doubling of the baseline creatinine.
Results: During the study period there were 60 MRSA nosocomial bacteremias. 50% of MRSA isolates had a vancomycin MIC = 1.5 µg/ml and 38.3% with MIC= 2 µg/ml; no upward vancomycin creep was observed. The proportion of isolates with an MIC≥ 2 µg/ml decreased by 50% after 2008 (p=0.03, Figure). The median age of patients was 4 months; the most common diagnosis was central-line associated bloodstream infection (CLA-BSI, 51.7%). The overall median duration of bacteremia was 2 days (IQR: 1-5). For patients without CLA-BSI, an MIC ≥2 µg/ml was associated with a longer duration of bacteremia (5 vs 2 days, p = 0.02). Increasing vancomycin troughs were not associated with a shorter duration of bacteremia; troughs ≥ 10 µg/ml were associated with a greater risk of AKI (44.4% vs 0%, p=0.02). For patients with CLA-BSI, neither vancomycin MIC or serum trough influenced the duration of bacteremia; however, line removal after day 2 of bacteremia was associated with a longer duration of bacteremia (4 vs 1 day, p=0.002).
Conclusion: Vancomycin MIC by E-test ≥2 µg/ml is associated with a delay in microbiologic cure in children with non-CLA-MRSA bacteremia. A decrease in vancomycin MICs in nosocomial MRSA bacteremia isolates was observed. For MRSA CLA-BSI, early line removal may have a greater therapeutic impact than either vancomycin MIC or serum trough. High vancomycin troughs were not associated with improved microbiologic outcomes in this population but with more AKI. Large studies are needed to further understand the impact of elevated vancomycin troughs on MRSA bacteremia in pediatrics.
E. Kok, None
K. G. Hulten, None
S. L. Kaplan, Pfizer: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient
E. Mason Jr, None