Table 1.
Examples of microbiome-sparing antimicrobial agents
| Name | Mechanism of Action | Pathogens Targeted | Advantages | Disadvantages |
|---|---|---|---|---|
| Lolamicin | Inhibits LolCDE complex, essential for lipoprotein transport in Gram-negative bacteria | Gram-negative bacteria (E. coli, K. pneumoniae, E. cloacae) | Preserves microbiota, novel mechanism | Limited to Gram-negative pathogens, not effective against P. aeruginosa or A. baumannii |
| SMT-738 | Targets LolC/E complex in Enterobacteriaceae | Gram-negative pathogens (Enterobacterales) | Microbiome-sparing, selective targeting | Early-stage development, limited clinical data; mainly selective for Enterobacterales |
| Afabicin | Inhibits FabI, an enzyme in fatty acid biosynthesis | S. aureus (Gram-positive bacteria) | Microbiome-sparing, targets Gram-positive pathogens | Narrow-spectrum, only effective against Gram-positive bacteria |
| Debio 1453 | Inhibits FabI, disrupting fatty acid biosynthesis | N. gonorrhoeae | Microbiome-sparing, rapid bactericidal activity | Limited data, in development stage |
| FP-100 (Hygromycin A) | Inhibits ribosomes of spirochetes | B. burgdorferi, Treponema pallidum, Fusobacterium nucleatum | Selectively targets periodontal pathogens without disrupting beneficial bacteria (Streptococcus parasanguinis, Bifidobacterium longum) | Still under development, limited data |
| FtsZ Inhibitors (e.g. TXA707, TXA709) | Inhibit polymerization of the FtsZ protein, disrupting bacterial cell division | Drug-resistant Gram-positive bacteria (MRSA, VRSA, DNSSA) | Synergistic with β-lactams, microbiome-sparing | Limited to Gram-positive pathogens, limited data |
| Ribaxamase | β-lactamase that targets excess IV β-lactam antibiotics in the GI tract | Prevents damage from broad-spectrum antibiotics in gut flora | Reduces dysbiosis, prevents antibiotic resistance and C. difficile infection | Limited to co-administration with IV β-lactams, early trial phase |
| Fidaxomicin | Inhibits bacterial RNA polymerase, disrupting transcription | C. difficile | Targets C. difficile, microbiome-sparing | Narrow-spectrum, limited to C. difficile infections |
| Ibezapolstat | Targets DNA polymerase IIIC (Pol IIIC) | C. difficile | 100% clinical cure rate in trials, microbiome-sparing | Early-stage trials, high cost |
| Ridinilazole | Binds to minor groove of DNA, inhibiting transcription | C. difficile | Targets C. difficile, microbiome-sparing | Limited to C. difficile infections, i.e. narrow-spectrum |