Background: MINO is one of the few options available to treat infections caused by ACB. Acquired MINO resistance (R) in ACB is associated with the presence of the TetB efflux pump. Previous studies demonstrated that in the absence of tetB, other combinations of intrinsic mechanisms of resistance do not produce MINO MICs above the current susceptibility breakpoint (≤ 4 µg/ml). The objective of this study was to assess whether tetB testing can discriminate between MINO S and non-susceptible (non-S).
Methods: 258 ACB isolates collected from multiple geographic sources were tested for MINO susceptibility using CLSI broth microdilution reference methods and for the tetB gene by PCR. MIC frequency distributions for the tetB positive (POS) and negative (NEG) sets of isolates were generated and assessed for the degree of separation. Proportions of MINO S and non-S isolates were calculated between tetB-POS and NEG strains. Fishers exact test was used to determine the association between TetB vs MINO susceptibility relationship.
Results: Of the 258 ACB, 172 and 86 isolates were found to be tetB-POS and NEG, respectively. MIC frequency distributions of tetB-POS and tetB-NEG sets demonstrated high degree of separation (Figure). Of the tetB-negative strains, all 86 (100%) had MINO MIC ≤4 µg/ml (MINO S according to FDA SB). Of 172 tetB-positive strains, 154 (89.5%) and 18 (10.5%) had MINO MIC > 4 µg/ml (MINO non-S) and ≤4 µg/ml, respectively. The difference in observed proportions was statistically significant according to Fishers exact test (p<0.0001).
Conclusion: tetB testing of clinical isolates might a potential rapid susceptibility test where the absence of tetB is predicts susceptibility to minocycline. Further studies are warranted.
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D. Rubio-Aparicio, The Medicines Company: Employee , Salary
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