Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.It is marketed by Merck, which acquired Cubist Pharmaceuticals in 2015, and had in turn bought the originating company, Optimer Pharmaceuticals. It is used for the treatment of Clostridioides difficile infection, which is also known as Clostridioides difficile-associated diarrhea or Clostridioides difficile-associated illness (CDI), and can develop into Clostridioides difficile colitis and pseudomembranous colitis. Fidaxomicin is available in a 200 mg tablet that is administered every 12 hours for a recommended duration of 10 days. Total duration of therapy should be determined by the patients clinical status. It is currently one of the most expensive antibiotics approved for use. A standard course costs upwards of £1350. Mechanism
Fidaxomicin binds to and prevents movement of the "switch regions" of bacterial RNA polymerase. Switch motion occurs during the opening and closing of the DNA:RNA clamp, a process that occurs throughout RNA transcription but is especially important in the opening of double-stranded DNA during the initiation of transcription.
Clitoromegaly (or macroclitoris) is an abnormal enlargement of the clitoris that is mostly congenital or acquired, though deliberately induced clitoris enlargement as a form of genital body modification is achieved through various uses of anabolic steroids, including testosterone. Clitoromegaly is not the same as normal enlargement of the clitoris seen during sexual arousal. Presentation
The different grade of genital ambiguity is commonly measured by the Prader classification, which ranges, in ascending order of masculinisation, from 1: female external genitalia with clitoromegaly through 5: pseudo-phallus looking like normal male external genitalia. Causes
Clitoromegaly is a rare condition and can be either present by birth or acquired later in life. If present at birth, congenital adrenal hyperplasia can be one of the causes, since in this condition the adrenal gland of the female fetus produces additional androgens and the newborn baby has ambiguous genitalia which are not clearly male or female. In pregnant women who received norethisterone during pregnancy, masculinization of the fetus occurs, resulting in hypertrophy of the clitoris; however, this is rarely seen nowadays due to use of safer progestogens. It can also be caused by the autosomal recessive congenital disorder known as Fraser syndrome.In acquired clitoromegaly, the main cause is endocrine hormonal imbalance affecting the adult person, including polycystic ovarian syndrome (PCOS) and hyperthecosis. Acquired clitoromegaly may also be caused by pathologies affecting the ovaries and other endocrine glands. These pathologies may include virulent (such as arrhenoblastoma) and neurofibromatosic tumors. Another cause is clitoral cysts.