(P107) CORRELATION BETWEEN DISK DIFFUSION AND AGAR DILUTION RESULTS WHEN TESTING GEPOTIDACIN AGAINST NEISSERIA GONORRHOEAE

Background:
Gepotidacin is a novel, first in class, triazaacenaphthylene antibacterial that inhibits bacterial type II topoisomerases by a unique mechanism of action, a distinct binding site and for most pathogens provides well-balanced inhibition of two different Type II topoisomerase enzymes. Gepotidacin recently completed a Phase III clinical trial to assess its effectiveness for the treatment of patients with uncomplicated urogenital gonorrhea. This study determined the correlation between gepotidacin disk diffusion zone diameters (ZD) and MICs by agar dilution using Neisseria gonorrhoeae isolates collected between 2018-2021.

Methods:
A total of 711 clinical isolates of N. gonorrhoeae were collected from sites in (n/percent of total): US (298/41.9), Australia (300/42.2), and India (133/15.9). A common inoculum was used to concurrently test the isolates against gepotidacin by disk diffusion using two disks (10 µg) manufactured by BD BBL and Mast Group Ltd and by agar dilution per CLSI guidelines. The combined data was analyzed by error-rate bounded method to select provisional ZD breakpoints (based on population distribution data only and not pharmacokinetic/pharmacodynamic or clinical data) using the dBETS software (CLSI M23).

Results:
MICs for gepotidacin ranged from ≤0.06 to 2 µg/mL with MIC50/90 value of 0.5/1 µg/mL. The range of ZD was 22–50 mm. The correlation coefficient (R2 value) between MIC and ZD was 0.28, which may reflect the low number of isolates with elevated gepotidacin MICs. Error-rate bounded analysis using tentative preliminary gepotidacin MIC breakpoints of ≤1/2/≥4 (Susceptible/Intermediate/Resistant [S/I/R]) suggested provisional disk diffusion ZD breakpoints of ≥27mm (S)/23-26 (I)/≤22mm (R). These breakpoints resulted in no very major or major errors, acceptable minor errors in the I+1 to I-1 range (20.2%) and the ≤I-2 range (0.6%), and an Index score of 0.252.

Conclusion:
Error rates were within acceptable CLSI limits. These provisional breakpoints should be re-evaluated as additional nonclinical and clinical data become available.