Introduction Mycoplasma and Ureaplasma spp. are important pathogens of the respiratory and urogenital tracts. Antimicrobial resistance limits treatment options. Gepotidacin (GEP), a novel triazaacenaphthylene topoisomerase II inhibitor that inhibits DNA replication by a mechanism and target distinct from fluoroquinolones was tested against 85 isolates of Mycoplasma pneumoniae (Mp), Mycoplasma hominis (Mh), Mycoplasma genitalium (Mg), Ureaplasma parvum (Up), and Ureaplasma urealyticum (Uu) in comparison to azithromycin (AZI), clindamycin (CLI), tetracycline (TET), levofloxacin (LEV), and moxifloxacin (MOX). Organisms tested included strains known to be resistant to TET, LEV, and/or AZI. This work was supported by GSK and funded through OTA HHSO100201300011C with HHS/BARDA.

Methods MICs were determined using broth microdilution in accordance with Clinical and Laboratory Standards Institute Guidelines.

Results GEP was active against 25 Mp, MIC range 0.032–0.125 µg/ml, including 5 that were AZI-resistant, with MIC₉₀ (0.125 µg/ml), equivalent to MOX. GEP was active against 10 Mg. MIC₉₀ (0.032 µg/ml) was 4-fold < MOX. GEP MICs against 25 Mh ranged from 0.5 to 2 µg/ml with MIC₉₀=2 µg/ml, making it less active than other agents, including MOX (MIC₉₀=0.125 µg/ml), with exceptions of 1 LEV and 2 TET-resistant organisms, for which GEP MICs were unaffected. GEP was less active against 25 Ureaplasma spp. (MIC range 1–8 µg/ml), MIC₉₀=8 µg/ml. There was no effect on GEP MICs in 9 Ureaplasma spp. with resistance to LEV, AZI, and/or TET. GEP minimum bactericidal concentrations for 4 isolates of Mg, 4 Mh, 4 Mp, 3 Uu, and 1 Up were >3 dilutions > MICs, indicating bacteriostatic effect.

Conclusion GEP warrants further study to treat infections due to Mycoplasma spp., particularly organisms resistant to other antimicrobials as it was active against isolates resistant to AZI, TET, LEV, and/or MOX.