In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium

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In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium

Jensen, Jørgen Skov (author): Department of Bacteria, Parasites and Fungi, Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark

Nørgaard, Christina (author): Department of Bacteria, Parasites and Fungi, Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark

Scangarella-Oman, Nicole (author): GlaxoSmithKline, Collegeville Pennsylvania, USA

Unemo, Magnus, 1970- (author): Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län

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2020-06-18
2020
English.
In: Emerging Microbes & Infections. - : Taylor & Francis. - 2222-1751. ; 9:1, s. 1388-1392

Related links:: https://doi.org/10.1...; show more...; https://www.tandfonl...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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 thein vitroactivity 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 MIC(90)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 (sigma FICI) of 0.5] for two isolates and additive/indifference (sigma FICI 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Mycoplasma genitalium
antimicrobial resistance
gepotidacin
in-vitro susceptibility testing
combination therapy

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ref (subject category)
art (subject category)

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