(P444) Determining the In vitro correlate of Susceptibility to Secnidazole in Trichomonas vaginalis

Wednesday, July 26, 2023

16:00 – 18:00 CST

Primary Presenter(s)

Keonte J. Graves, MS (he/him/his)

Graduate Student Trainee/Student Intern
Division of Infectious Diseases, University of Alabama at Birmingham
Birmingham, Alabama, United States

Co-author(s)

JN

Jan Novak

The University of Alabama at Birmingham, United States
WS

W. Evan Secor

Centers for Disease Control and Prevention, United States
Christina A. Muzny, MD, MSPH (she/her/hers)

Associate Professor of Medicine, Epidemiology, and Obstetrics & Gynecology
Division of Infectious Diseases, University of Alabama at Birmingham
Birmingham, Alabama, United States

Background: Trichomonas vaginalis is the most common non-viral sexually transmitted infection worldwide. Drugs from the 5-nitroimidazole class are the only FDA-approved treatments. Secnidazole (SEC) is a next-generation oral 5-nitroimidazole recently FDA-approved for the treatment of trichomoniasis. We aimed to determine the in vitro minimum lethal concentration (MLC) of SEC that correlates with clinical susceptibility of T. vaginalis among isolates obtained from women in a delayed-treatment trial of SEC vs. placebo.

Methods: T. vaginalis isolates from women participating in a SEC randomized controlled trial (RCT) were tested in susceptibility assays for metronidazole (MTZ), tinidazole (TDZ), and SEC under aerobic conditions. The lowest concentration at which no viable parasite(s) were observed was recorded as the MLC for each drug. Data from isolates obtained from women who cured following SEC treatment were analyzed to determine the median and 95^th percentile MLC for each drug. Using the 95^th percentile MLC of susceptible isolates as the cutoff for potential in vitro resistance, we compared the agreement of the in vitro SEC MLC for each isolate with the corresponding treatment outcome.

Results: Of 50 isolates tested to date, 5 (10%) were from women who failed SEC treatment while 45 (90%) were from women who cured infection after SEC treatment. The median MLC of isolates obtained from women successfully treated with SEC was 3.1 µg/ml and the 95^th percentile was 12.5 µg/ml. Of the women who cured following SEC treatment, 44/45 (97.8%) of isolates had MLCs ≤12.5 µg/ml; for isolates obtained from women who failed SEC treatment, 3/5 (60%) had MLCs >12.5 µg/ml. The median MLCs for MTZ and TDZ were 6.3 and 1.6 µg/ml, respectively, which are similar to values obtained at CDC. The 95^th percentile MLCs were 46.4 µg/ml for MTZ and 100 µg/ml for TDZ.

Conclusion: T. vaginalis isolates with SEC MLCs ≤12.5 µg/ml correlated with successful treatment outcomes in a recent RCT. These results suggest that this cutoff will be useful for in vitro evaluation of SEC treatment failures and development of alternative treatment regimens for treatment failures in trichomoniasis.