376. Staphylococcus aureus Bacteremia: Is Higher Vancomycin Minimum Inhibitory Concentration Associated with Higher Mortality? A Meta-analysis and Meta-regression
Session: Poster Abstract Session: MRSA, MSSA, Enterococci
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
  • IDWeek_Poster_SA-MIC-Final.pdf (1.1 MB)
  • Background: Conflicting data have been published regarding mortality outcomes and higher vancomycin minimum inhibitory concentration (MIC). We systematically reviewed mortality and vancomycin MIC data in patients with Staphylococcus aureusbacteremia (SAB).

    Methods: Studies reporting mortality and vancomycin MIC in patients with SAB were included. Random-effects modeling, Tau-squared, and meta-regression were performed.

    Results: 8,039 SAB episodes were selected from 38 studies. Mean age was 63yo and overall mortality was 25.3%. The absolute risk difference (RD) of death with vancomycin MIC ≥ 1.5 mcg/mL (high) compared to MIC < 1.5 mcg/mL (low) was 2.0% (95%CI -2.1%, 6.0%); p=0.340;T2=0.008. In studies that included only MRSA infections (N=6032) the RD was 1.7% (95%CI -3.1%,6.5%); p=0.481; T2=0.009; and studies that included heteroresistance (N=1104) showed a lower risk of death: RD=-9.6% (95%CI -19%, -0.2%); p=0.045; T2=0.004. Analysis stratified by MIC testing methodology revealed the following for high vs. low MIC: Broth Microdilution (N=1852): RD=1.2% (95%CI -7.8%,10%);p=0.80;T2=0.012; Etest (N=5840): RD=1.6% (95%CI -3.1%,6.4%); p=0.499; T2=0.007; Automated (N=347): RD=10.4% (95%CI -3.9%, 24.6%); p=0.80; T2=0.009. RD for specific MIC cut-offs: MIC ≥ 1.5 (N=3714) RD=1.2%(95%CI -4.3%,6.6%);p=0.671;T2=0.005; MIC ≥ 2 (N=3818) RD=4.2%(95%CI-2.5%, 11%); p=0.223; T2=0.014; MIC ≥ 4 (N=164) RD=-6.4% (95%CI -32%, 19%); p=0.620; T2=0.015; MIC ≥ 8 (N=343) RD=-1.8%(95%CI -18%,14%);p=0.822;T2=0. Sensitivity analysis demonstrated similar risk of death across study designs: Prospective (N=1445): RD=2.9%(95%CI -8.4%,14%);p=0.617;T2=0.014; Retrospective (N=6594): RD=1.6%(95%CI -2.7%,5.9%);p=0.455;T2=0.004; and across outcomes: 30-day mortality (N=4987): RD=1.6%(95%CI -4.5%,7.6%);p=0.614;T2=0.012; hospital mortality (N=3052): RD=1.9%(95%CI -2.0%,5.9%);p=0.341;T2=0. Meta-regression showed that the mortality risk difference was influenced by the control mortality rate: RD was decreased by 0.37% for every 1% mortality increase in the control (low MIC) group (p=0.001).

    Conclusion: Higher vancomycin MIC isnot associated with higher mortality rates in patients with SAB.  The large sample size, significant influence by control mortality, and consistent findings across different assays, MIC cut-offs, methicillin susceptibility status, and study designs strongly support this finding.

    Trevor C. Van Schooneveld, MD1, Andre C. Kalil, MD, MPH2, Mark E. Rupp, MD, FIDSA, FSHEA2 and Paul Fey, PhD3, (1)Internal Medicine, University of Nebraska Medical Center, Omaha, NE, (2)Internal Med., Univ. of Nebraska Med. Ctr., Omaha, NE, (3)Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE


    T. C. Van Schooneveld, Cubist: Research Contractor and Scientific Advisor, Consulting fee and Research support

    A. C. Kalil, None

    M. E. Rupp, None

    P. Fey, None

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