Фидаксомицин

Описание

Fidaxomicin (OPT-80) was approved by the U.S. FDA in May 2011 for the treatment of Clostridium difficile-associated diarrhea (CDAD), joining metronidazole and vancomycin as drugs recommended for treatment of C. difficile infections (CDI). Fidaxomicin, also known as lipiarmycin and tiacumicin, is an 18-membered macrolide natural product that was first reported in mid-1970s and is produced by fermentation. Fidaxomicin and its primary metabolite OP-1118, which results from hydrolysis of the isobutyryl ester, are narrowspectrum antibacterial agents with activity against gram-positive aerobic and anaerobic organisms, but not against gram-negative organisms. Fidaxomicin and OP-1118 exert their antibacterial activity by inhibiting bacterial RNA polymerase, thereby inhibiting bacterial protein synthesis.
The MIC90 (minimum inhibitory concentration to kill 90% of bacteria) for fidaxomicin against C.difficile is 0.125–0.25 μg/mL; OP- 1118 is 4- to 16-fold less potent than the parent compound. Fidaxomicin has been reported to spare native intestinal flora such as Bacteroides spp. and as such, may prevent selection of drug-resistant bacteria. Fidaxomicin is bactericidal to C. difficile and has a low propensity for resistance development with no cross-resistance to existing antibiotics. Fidaxomicin shows minimal systemic absorption following oral administration in preclinical studies and humans.

Использование

Fidaxomicin is a recently marketed antibiotic with a confusing history dating back to its original isolation in 1975. Fidaxomicin is the major analogue of a family of macrocyclic lactones, isolated independently by three different groups from cultures belonging to three different genera (Actinoplanes, Dactylosporangium and Micromonospora) known as lipiarmycin A3, tiacumicin B and clostomicin B1, respectively. Fidaxomicin is a narrow spectrum antibiotic with excellent activity against Gram positive bacteria, notably Clostridium difficile. Fidaxomicin acts in the gastrointestinal tract without undue disruption to gut microbial flora.

Определение

ChEBI: An 18-membered macrolide that is a fermentation product obtained from the Actinomycete Dactylosporangium aurantiacum. A narrow spectrum antibiotic used for treatment of Clostridium difficile-related infections.

Фармацевтические приложения

Formerly known as difimicin. An 18-membered macrocyclic compound related to the tiacumicin group of antibiotics rather than conventional macrolides. It is active against staphylococci (MIC 0.5–2 mg/L) and most anaerobic Grampositive bacilli and cocci, but Gram-negative bacilli, including Gram-negative anaerobes, are resistant. It is very poorly absorbed when given orally and most interest surrounds its activity against C. difficile (MIC 0.12–0.25 mg/L). Such data as are presently available from clinical trials suggest that it is as safe and effective in the treatment of C. difficile-associated diarrhea as vancomycin.