1602. Benefit:Risk Evaluation in Diagnostics: An Example Comparing Two Rapid Molecular Diagnostics Testing Imipemem Susceptibility in Acinetobacter spp.
Session: Poster Abstract Session: ESBL and CRE Diagnostics
Saturday, October 10, 2015
Room: Poster Hall
  • ARLG_Benefit_Risk_Poster_Evans.pdf (707.2 kB)
  • Background: Methods to assess benefit:risk of diagnostic methods to help clinicians treat multidrug-resistant Acinetobacter spp. are needed. Important considerations include effects on diagnostic yield [(i.e., the distribution of true resistance (TR), false resistance (FR), true susceptibility (TS), and false susceptibility (FS)], which is affected by the susceptibility rate.

    Methods: We developed a slide-rule profile plot of the expected diagnostic yield as a function of the susceptibility rate. The number-needed-to-test (NNT) for susceptibility (NNT-S) [i.e., the expected number of susceptible patients that must be tested with one test (vs. another test) to result in one additional TS] was defined, as was the NNT for resistance (NNT-R). We apply the method to the evaluation of two rapid molecular diagnostic platforms [PCR/ESI-MS and Molecular Beacons™ (MB)] utilized for imipenem susceptibility testing based on the presence/absence of blaMBLs and blaOXA genes vs. reference MIC determination in Acinetobacter spp. (Ab) infection. Expected diagnostic yield was evaluated based on a population of 12,000 Ab cases.

    Results: When the imipenem susceptibility rate is 40%, the expected yield for MB is (TR=6408; FR=384; TS=4416; FS=792) and for PCR/ESI-MS is (TR=6912; FR=816; TS=3984; FS=288). Thus the between-platform difference in expected yield is 504 more TR for PCR/ESI-MS and 432 more TS for MB. When the susceptibility rate is 60%, the difference in expected yield is 336 more TR for PCR/ESI-MS and 648 more TS for MB (Figure 1). Tradeoffs for any susceptibility rate can be obtained (Figure 2). The NNT-S is 11.1 (MB vs. PCR/ESI-MS), and the NNT-R is 14.3 (PCR/ESI-MS vs. MB).


    Conclusion: Here we develop profile plots to illustrate how diagnostic yield varies by susceptibility rate. Between-platform differences in TR and TS plotted as a function of the susceptibility rates and NNTs provide a relative comparison of two AST methodologies. Applying these approaches helps us understand the benefits and risks of each new diagnostic platform when applied to treatment decisions.


      Figure 1: Slide-Rule Profile Plots of Diagnostic Yield for Imipenem Susceptibility Testing in Ab





    Figure 2: Between-Platform Difference in TR and TS as a Function of the Susceptibility Rate




    Scott Evans, PhD, MS1, Hongyu Jiang, MS2, Andrea Hujer, BS3, Kristine M. Hujer, BS4, Claudia Manca, PhD5, Carol Hill, PhD6, Barry N. Kreiswirth, PhD7, Michael R. Jacobs, MD, PhD8, Liang Chen, PhD5, Rangarajan Sampath, PhD9, Thomas Hall, PhD10, Christine Marzan, PhD10 and Robert A. Bonomo, MD11, (1)Harvard University, Boston, MA, (2)Biostatistics, Harvard School of Public Health, Boston, MA, (3)Case Western Reserve University, Cleveland, OH, (4)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (5)Public Health Research Institute - Rutgers University, Newark, NJ, (6)Duke Clinical Research Institute, Durham, NC, (7)Phri TB Center, Rutgers University, Newark, NJ, (8)Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, (9)Ibis Biosciences, Inc, Carlsbad, CA, (10)Ibis Biosciences, Carlsbad, CA, (11)Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, OH


    S. Evans, None

    H. Jiang, None

    A. Hujer, None

    K. M. Hujer, None

    C. Manca, None

    C. Hill, None

    B. N. Kreiswirth, None

    M. R. Jacobs, None

    L. Chen, None

    R. Sampath, Abbott: Employee , Salary

    T. Hall, Ibis Biosciences, an Abbott Company: Employee , Salary

    C. Marzan, Ibis Biosciences, an Abbott Company: Employee , Salary

    R. A. Bonomo, AstraZeneca: Grant Investigator , Research grant
    Merck: Grant Investigator , Research grant
    Melinta: Grant Investigator , Research grant
    VA Merit Review Board: Grant Investigator , Research grant
    NIH: Grant Investigator , Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.