Back to Search
Start Over
In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium
- Source :
- Emerging Microbes & Infections, article-version (VoR) Version of Record
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- Mycoplasma genitalium has developed resistance to first-line azithromycin and second-line moxifloxacin. Third-line pristinamycin is only 75% effective. Gepotidacin, a novel triazaacenaphthylene topoisomerase II inhibitor, blocks bacterial DNA replication. We determined the in vitro activity of gepotidacin alone and in combination with doxycycline against a diverse collection of Mycoplasma genitalium isolates (n = 54). Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by a Vero-cell culture method. Macrolide resistance was present in 31 (57%) isolates, fluoroquinolone resistance in 18 (33%) isolates, and 17 (31%) had dual resistance. Synergy testing was performed for gepotidacin and doxycycline by checkerboard analysis for two macrolide- and two dual-resistant isolates. Gepotidacin was active against all 54 M. genitalium isolates with median and modal MICs of 0.125 mg/L and MIC90 of 0.25 mg/L (range ≤0.016–0.5 mg/L). No difference in gepotidacin MIC between macrolide-resistant and -susceptible isolates (p = 0.24) or between fluoroquinolone-, dual-resistant and -susceptible isolates (p = 0.2) was demonstrated. Gepotidacin MBCs were available for 44 M. genitalium isolates with median MIC of 0.064 mg/L and median MBC of 0.125 mg/L. All isolates had ≤4-fold difference between MIC and MBC, suggesting bactericidal effect for gepotidacin. Checkerboard analysis indicated synergistic effect for gepotidacin in combination with doxycycline [fractional inhibitory concentration index (ΣFICI) of 0.5] for two isolates and additive/indifference (ΣFICI at 0.62 and 0.75) for two isolates. Gepotidacin warrants further evaluation in clinical treatment trials for M. genitalium. Combination therapy with doxycycline should be clinically studied to assess effect and potential protection against development and/or spread of gepotidacin resistance.
- Subjects :
- 0301 basic medicine
Gepotidacin
Epidemiology
gepotidacin
030106 microbiology
Immunology
Mycoplasma genitalium
Drug resistance
in-vitro susceptibility testing
Azithromycin
Microbiology
combination therapy
03 medical and health sciences
chemistry.chemical_compound
Antibiotic resistance
Moxifloxacin
Virology
Drug Discovery
medicine
antimicrobial resistance
Doxycycline
biology
business.industry
General Medicine
biology.organism_classification
bacterial infections and mycoses
Pristinamycin
030104 developmental biology
Infectious Diseases
chemistry
Parasitology
Original Article
business
medicine.drug
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 22221751
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Emerging Microbes & Infections
- Accession number :
- edsair.doi.dedup.....f1e6c6365ac456d5fbc25f5cba72c342