Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.
J Antimicrob Chemother
; 78(8): 1900-1908, 2023 08 02.
Article
em En
| MEDLINE
| ID: mdl-37294305
ABSTRACT
BACKGROUND:
Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation.OBJECTIVES:
To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota.METHODS:
Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily.RESULTS:
Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model.CONCLUSIONS:
Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microbiota
/
Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Suíça