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
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