Fidaxomicin
Encyclopedia
Fidaxomicin is the first in a new class of narrow spectrum macrocyclic
antibiotic
drugs. It is a fermentation product obtained from the actinomycete Dactylosporangium
aurantiacum subspecies hamdenesis. Fidaxomicin is non-systemic, meaning it is minimally absorbed into the bloodstream, it is bactericidal, and it has demonstrated selective eradication of pathogenic Clostridium difficile
with minimal disruption to the multiple species of bacteria
that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon can reduce the probability of Clostridium difficile infection recurrence.
It is marketed by Optimer Pharmaceuticals for treatment of Clostridium difficile infection. Fidaxomicin is available in a 200mg tablet that is administered every 12 hours for a recommended duration of 10 days. Total duration of therapy should be determined by the patient's clinical status.
It works by inhibiting the bacterial enzyme RNA polymerase
, resulting in the death of Clostridium difficile. It is active against gram positive bacteria especially clostridia
. The minimal inhibitory concentration (MIC) range for C. difficile (ATCC 700057) is 0.03–0.25(μg/mL).
for the treatment of Clostridium difficile infection (CDI) The study met its primary endpoint of clinical cure, showing that fidaxomicin was non-inferior to oral vancomycin (92.1% vs. 89.8%). In addition, the study met its secondary endpoint of recurrence: 13.3% of the subjects had a recurrence with fidaxomicin vs. 24.0% with oral vancomycin
. The study also met its exploratory endpoint of global cure (77.7% for fidaxomicin vs. 67.1% for vancomycin). Clinical cure was defined as patients requiring no further CDI therapy two days after completion of study medication. Global cure was defined as patients who were cured at the end of therapy and did not have a recurrence in the next 4 weeks.
Fidaxomicin was shown to be as good as the current standard-of-care, vancomycin, for treating CDI in a Phase III trial published in February of 2011. The authors also reported significantly fewer recurrences of infection, a frequent problem with C. difficile, and similar drug side effects.
The drug won an FDA advisory panel's unanimous approval on April 10, 2011. and full FDA approval on May 27, 2011.
Macrocycle
A macrocycle is, as defined by IUPAC, "a cyclic macromolecule or a macromolecular cyclic portion of a molecule." In the chemical literature, organic chemists may consider any molecule containing a ring of nine or more atoms to be a macrocycle...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
drugs. It is a fermentation product obtained from the actinomycete Dactylosporangium
Dactylosporangium
Dactylosporangium is a genus in the phylum Actinobacteria .-Etymology:The name Dactylosporangium derives from:Greek noun daktulos, finger; Greek noun spora , a seed, and in biology a spore; Greek neuter gender noun angeion , vessel ; New Latin neuter gender noun Dactylosporangium an organism with...
aurantiacum subspecies hamdenesis. Fidaxomicin is non-systemic, meaning it is minimally absorbed into the bloodstream, it is bactericidal, and it has demonstrated selective eradication of pathogenic Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
with minimal disruption to the multiple species of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon can reduce the probability of Clostridium difficile infection recurrence.
It is marketed by Optimer Pharmaceuticals for treatment of Clostridium difficile infection. Fidaxomicin is available in a 200mg tablet that is administered every 12 hours for a recommended duration of 10 days. Total duration of therapy should be determined by the patient's clinical status.
It works by inhibiting the bacterial enzyme RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
, resulting in the death of Clostridium difficile. It is active against gram positive bacteria especially clostridia
Clostridia
The Clostridia are a class of Firmicutes, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the genus Clostridium are all Gram-positive and have the ability to...
. The minimal inhibitory concentration (MIC) range for C. difficile (ATCC 700057) is 0.03–0.25(μg/mL).
Clinical trials
Good results were reported in 2009 from a North American phase III trial comparing it with oral vancomycinVancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
for the treatment of Clostridium difficile infection (CDI) The study met its primary endpoint of clinical cure, showing that fidaxomicin was non-inferior to oral vancomycin (92.1% vs. 89.8%). In addition, the study met its secondary endpoint of recurrence: 13.3% of the subjects had a recurrence with fidaxomicin vs. 24.0% with oral vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
. The study also met its exploratory endpoint of global cure (77.7% for fidaxomicin vs. 67.1% for vancomycin). Clinical cure was defined as patients requiring no further CDI therapy two days after completion of study medication. Global cure was defined as patients who were cured at the end of therapy and did not have a recurrence in the next 4 weeks.
Fidaxomicin was shown to be as good as the current standard-of-care, vancomycin, for treating CDI in a Phase III trial published in February of 2011. The authors also reported significantly fewer recurrences of infection, a frequent problem with C. difficile, and similar drug side effects.
The drug won an FDA advisory panel's unanimous approval on April 10, 2011. and full FDA approval on May 27, 2011.