Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study
<i>Stenotrophomonas maltophilia</i> is increasingly recognized as a nosocomial bacterial pathogen with a multi-drug resistance profile. In this study, the novel drug gepotidacin, the first compound of the novel triazaacenaphthylene topoisomerase inhibitor antibiotics class, was evaluated...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/2/192 |
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| author | Maike Isabell Sanders Eyhab Ali Jan Buer Joerg Steinmann Peter-Michael Rath Hedda Luise Verhasselt Lisa Kirchhoff |
| author_facet | Maike Isabell Sanders Eyhab Ali Jan Buer Joerg Steinmann Peter-Michael Rath Hedda Luise Verhasselt Lisa Kirchhoff |
| author_sort | Maike Isabell Sanders |
| collection | DOAJ |
| description | <i>Stenotrophomonas maltophilia</i> is increasingly recognized as a nosocomial bacterial pathogen with a multi-drug resistance profile. In this study, the novel drug gepotidacin, the first compound of the novel triazaacenaphthylene topoisomerase inhibitor antibiotics class, was evaluated on its activity against clinical <i>S. maltophilia</i> isolates. Ninety-nine <i>S. maltophilia</i> isolates plus reference strain K279a (N = 100) were tested on their susceptibility towards gepotidacin in a broth microdilution. Additional susceptibility testing was performed towards the commonly applied combination trimethoprim/sulfamethoxazole (TMP/SXT), moxifloxacin, and levofloxacin. The time–kill kinetic of gepotidacin was observed in a time–kill assay. The greater wax moth <i>Galleria mellonella</i> was used to determine the activity of gepotidacin against <i>S. maltophilia </i>in vivo. Gepotidacin showed minimum inhibitory concentrations (MICs) between 0.25 and 16 mg/L (MIC<sub>50</sub>: 2 mg/L; MIC<sub>90</sub>: 8 mg/L), independently of its susceptibility towards TMP/SXT. The five TMP/SXT resistant strains exhibited gepotidacin MICs from 1 to 4 mg/L. The <i>S. maltophilia</i> strains resistant to the assessed fluoroquinolones showed in parts high MICs of gepotidacin. The time–kill assay revealed a time- and strain-dependent killing effect of gepotidacin. In vivo, injection of gepotidacin increased the survival rate of the larvae from 61 % to 90 % after 2 days. This study showed antimicrobial effects of gepotidacin towards <i>S. maltophilia</i>. |
| first_indexed | 2024-03-09T22:46:54Z |
| format | Article |
| id | doaj.art-d981ccdbbbd343f2b1cd8b40198ed9bb |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T22:46:54Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-d981ccdbbbd343f2b1cd8b40198ed9bb2023-11-23T18:27:58ZengMDPI AGAntibiotics2079-63822022-02-0111219210.3390/antibiotics11020192Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo StudyMaike Isabell Sanders0Eyhab Ali1Jan Buer2Joerg Steinmann3Peter-Michael Rath4Hedda Luise Verhasselt5Lisa Kirchhoff6Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany<i>Stenotrophomonas maltophilia</i> is increasingly recognized as a nosocomial bacterial pathogen with a multi-drug resistance profile. In this study, the novel drug gepotidacin, the first compound of the novel triazaacenaphthylene topoisomerase inhibitor antibiotics class, was evaluated on its activity against clinical <i>S. maltophilia</i> isolates. Ninety-nine <i>S. maltophilia</i> isolates plus reference strain K279a (N = 100) were tested on their susceptibility towards gepotidacin in a broth microdilution. Additional susceptibility testing was performed towards the commonly applied combination trimethoprim/sulfamethoxazole (TMP/SXT), moxifloxacin, and levofloxacin. The time–kill kinetic of gepotidacin was observed in a time–kill assay. The greater wax moth <i>Galleria mellonella</i> was used to determine the activity of gepotidacin against <i>S. maltophilia </i>in vivo. Gepotidacin showed minimum inhibitory concentrations (MICs) between 0.25 and 16 mg/L (MIC<sub>50</sub>: 2 mg/L; MIC<sub>90</sub>: 8 mg/L), independently of its susceptibility towards TMP/SXT. The five TMP/SXT resistant strains exhibited gepotidacin MICs from 1 to 4 mg/L. The <i>S. maltophilia</i> strains resistant to the assessed fluoroquinolones showed in parts high MICs of gepotidacin. The time–kill assay revealed a time- and strain-dependent killing effect of gepotidacin. In vivo, injection of gepotidacin increased the survival rate of the larvae from 61 % to 90 % after 2 days. This study showed antimicrobial effects of gepotidacin towards <i>S. maltophilia</i>.https://www.mdpi.com/2079-6382/11/2/192<i>Stenotrophomonas maltophilia</i>gepotidacintriazaacenaphthylenetopoisomerase inhibitor<i>Galleria mellonella</i>cystic fibrosis |
| spellingShingle | Maike Isabell Sanders Eyhab Ali Jan Buer Joerg Steinmann Peter-Michael Rath Hedda Luise Verhasselt Lisa Kirchhoff Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study Antibiotics <i>Stenotrophomonas maltophilia</i> gepotidacin triazaacenaphthylene topoisomerase inhibitor <i>Galleria mellonella</i> cystic fibrosis |
| title | Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study |
| title_full | Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study |
| title_fullStr | Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study |
| title_full_unstemmed | Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study |
| title_short | Antibacterial Activity of the Novel Drug Gepotidacin against <i>Stenotrophomonas maltophilia</i>—An In Vitro and In Vivo Study |
| title_sort | antibacterial activity of the novel drug gepotidacin against i stenotrophomonas maltophilia i an in vitro and in vivo study |
| topic | <i>Stenotrophomonas maltophilia</i> gepotidacin triazaacenaphthylene topoisomerase inhibitor <i>Galleria mellonella</i> cystic fibrosis |
| url | https://www.mdpi.com/2079-6382/11/2/192 |
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