Fidaxomicin (OPT-80), identified as a macrocyclic antibiotic, acts as a potent inhibitor of RNA polymerase when taken orally. It exhibits a narrow antibacterial spectrum, notably showing strong activity against Clostridium difficile (MIC90=0.12 μg/mL), making it valuable for research into Clostridium difficile infections (CDI)[1].[2].[3].
体内研究
Administering Fidaxomicin orally (0-5 mg/kg, once daily for five days) effectively protects against death and relapse in a hamster model of pseudomembranous colitis[3].
体外研究
Fidaxomicin selectively eradicates pathogenic Clostridium difficile with minimal disruption to the multiple species of bacteria that make up the normal, healthy intestinal flora[1].
Fidaxomicin demonstrates no inhibitory effect on the common gut commensals, with a MIC90 exceeding 1024 μg/mL[2].
To study the effect of Fidaxomicin on toxin A-induced TNF-α expression and NF-κB phosphorylation. Results showed that Fidaxomicin dose-dependently inhibited toxin A-induced NF-κB phosphorylation and TNF-α expression.
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01513-17.
A549 cells
12.2 ± 3.6 µM (EC50)
48 hours
Evaluate the inhibitory effect of Fidaxomicin on ZIKV infection, showing an EC50 value of 12.2 ± 3.6 μM
BMC Med. 2020 Jul 31;18(1):204.
Huh7 cells
7.7 ± 1.7 µM (EC50)
48 hours
Evaluate the inhibitory effect of Fidaxomicin on ZIKV infection, showing an EC50 value of 7.7 ± 1.7 μM
BMC Med. 2020 Jul 31;18(1):204.
Vero cells
11.7 ± 2.1 µM (EC50)
48 hours
Evaluate the inhibitory effect of Fidaxomicin on ZIKV infection, showing an EC50 value of 11.7 ± 2.1 μM
BMC Med. 2020 Jul 31;18(1):204.
SNB19 cells
6.0 ± 1.0 µM (EC50)
48 hours
Evaluate the inhibitory effect of Fidaxomicin on ZIKV infection, showing an EC50 value of 6.0 ± 1.0 μM
BMC Med. 2020 Jul 31;18(1):204.
Human colonic CCD-18Co fibroblasts
20 µM
6 hours
To evaluate the effect of Fidaxomicin on C. difficile toxin A-mediated cell rounding. Results showed that Fidaxomicin partially reduced toxin A-induced cell rounding.
To evaluate the effect of Fidaxomicin on Clostridium difficile toxin A- and B-induced apoptosis. Results showed that Fidaxomicin significantly reduced toxin A- and B-mediated apoptosis.
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01513-17.
Mycobacterium tuberculosis RNAP σA holoenzyme
75 nM
Measure RNAP inhibitory activity
Mol Cell. 2018 Apr 5;70(1):60-71.e15.
Clostridium difficile
≤0.001 –1μg/mL
To evaluate the antibacterial activity of fidaxomicin against C. difficile, showing an MIC range of ≤0.001 –1μg/mL and an MIC90 of 0.5 μg/mL.
Evaluate the effect of RbpA mutants on Fdx sensitivity, showing that NTT deletion leads to increased Fdx resistance, while R79A and R88A mutants increase Fdx sensitivity.
J Biol Chem. 2022 Apr;298(4):101752
Ifnar1−/− mice
ZIKV infection model
Tail vein injection
20 or 10 mg/kg
Once daily for 7 days
Evaluate the therapeutic effect of Fidaxomicin on ZIKV-infected mice, showing significant improvement in survival rate and alleviation of pathological damage
BMC Med. 2020 Jul 31;18(1):204.
Mice
Ileal loop model
Local administration
20 μM
30 min pretreatment followed by exposure to toxin A for 4 h
To evaluate the effect of Fidaxomicin on Clostridium difficile toxin A-mediated intestinal inflammation. Results showed that Fidaxomicin significantly inhibited toxin A-mediated NF-κB phosphorylation and tissue damage.
Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01513-17.
C57BL/6 mice
C. difficile toxin A-induced ileitis model
Ileal loop injection
5, 10, or 20 μM
Single dose, evaluated after 4 hours
To evaluate the effect of Fidaxomicin on C. difficile toxin A-mediated ileal inflammation. Results showed that Fidaxomicin significantly reduced toxin A-induced tissue damage, IL-1β expression, and ERK phosphorylation.
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