1308. Microbiological Cure Rates and Antimicrobial Susceptibility of Neisseria gonorrhoeae to ETX0914 (AZD0914) in a Phase II Treatment Trial for Urogenital Gonorrhea
Session: Poster Abstract Session: Clinical Infectious Diseases: Sexually Transmitted Infections
Friday, October 28, 2016
Room: Poster Hall
Posters
  • NIH_AZGC_micro_efficacy_IDweek2016_AS_FINAL_2.pdf (285.1 kB)
  • Background: The development of new antimicrobial agents to combat multi-drug resistant Neisseria gonorrhoeae (NG) is a national public health priority. ETX0914 is a novel spiropyrimidinetrione antibiotic that inhibits deoxyribonucleic acid biosynthesis by accumulation of double strand cleavages. We analyzed NG isolates collected from a multi-center, phase II trial of ETX0914 versus ceftriaxone to determine microbiological cure rates and antimicrobial susceptibility to these agents.

    Methods: Men and women with signs/symptoms of urogenital gonorrhea, confirmed urogenital gonorrhea or sexual contact with an individual diagnosed with gonorrhea in the past 14 days were eligible for enrollment. Participants were randomized to ETX0914 2000mg or 3000mg orally or ceftriaxone 500mg intramuscular injection. NG culture specimens were collected from urethral or cervical sites at baseline and at 6+2 days after treatment, and from pharyngeal and rectal sites among a subset of participants who reported relevant exposures. Agar dilutions were performed on NG isolates to determine minimum inhibitory concentrations (MIC) of ETX0914 required to inhibit 50% and 90% of NG strains (MIC50 and MIC90, respectively).

    Results: From November 2014 through December 2015, we enrolled 167 men and 12 women from whom NG was identified in 131 urethral, 9 cervical, 23 pharyngeal, and 14 rectal specimens. In the per protocol population, 48/49 (98%) participants in the ETX0914 2000mg arm, 47/47 (100%) in the ETX0914 3000mg arm, and 21/21 (100%) in the ceftriaxone arm achieved microbiological cure. The MIC50/90 determined from urethral/cervical specimens was 0.125/0.250 ug/mL for 2000mg ETX0914, and 0.125/0.125 ug/mL for 3000mg ETX0914. None of the baseline isolates demonstrated resistance to ETX0914 or ceftriaxone defined as MIC > 0.5 ug/mL and > 0.125 ug/mL, respectively. The proportion of isolates with ciprofloxacin MIC > 1.0 ug/mL were 11% from urethral, 13% from cervical, and 11% from pharyngeal specimens; 3% of urethral isolates and 5% of pharyngeal isolates had azithromycin MIC > 2.0 ug/ml.

    Conclusion: ETX0914 was effective in eradicating NG from urogenital sites, and had acceptable MICs among NG isolates including those resistant to ciprofloxacin or azithromycin.

    Arlene C. Seña, MD, MPH1, Stephanie N. Taylor, MD2, Jeanne Marrazzo, MD, MPH, FIDSA, FACP3, Byron E. Batteiger, MD4, Edward W. Hook III, MD5, Michael R Wierzbicki, PhD6, Hannah Kwak, MS6, Shacondra M. Johnson, BSPH7, Kenneth Lawrence, PharmD8 and John Mueller, PhD8, (1)Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, (2)Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, (3)Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL, (4)Indiana University, Indianapolis, IN, (5)Medicine (Infectious Diseases), University of Alabama at Birmingham, Birmingham, AL, (6)EMMES Corporation, Rockville, MD, (7)FHI360, Durham, NC, (8)Entasis Therapeutics, Waltham, MA

    Disclosures:

    A. C. Seña, None

    S. N. Taylor, None

    J. Marrazzo, None

    B. E. Batteiger, None

    E. W. Hook III, None

    M. R. Wierzbicki, None

    H. Kwak, None

    S. M. Johnson, None

    K. Lawrence, None

    J. Mueller, Entasis Therapeutics: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.