opt-80 and Clostridium-Infections

To evaluate the efficacy and safety of fidaxomicin for the treatment of Clostridium difficile infection.. Literature retrieval was accessed through MEDLINE (1966-January 2010) and International Pharmaceutical Abstracts (1970-January 2010) using the terms OPT-80, difimicin, PAR-101, fidaxomicin, tiacumicin, lipiarmycin, and Clostridium difficile. In addition, reference citations from publications identified were reviewed.. All articles published in English that were identified from the data sources were evaluated and pertinent information was included.. Fidaxomicin is an 18-membered macrocyclic antibiotic with activity against gram-positive aerobes and anaerobes, including C. difficile. Microbiologic studies comparing in vitro activity of fidaxomicin with that of metronidazole and vancomycin have shown good activity against all strains of C. difficile tested; however, minimum inhibitory concentrations were consistently lower for fidaxomicin. Studies showed that fidaxomicin lacks activity against gram-negative pathogens, thereby preserving normal gastrointestinal flora. Small pharmacokinetic trials have shown that fidaxomicin administration leads to low concentrations in plasma, high concentrations in stool, and a postantibiotic effect of greater than 24 hours, all of which are potentially advantageous characteristics for treating C. difficile infection. Data from 2 Phase 2A trials and 1 Phase 3 (multicenter, randomized, double-blind) trial suggest that fidaxomicin is effective for the treatment of mild-to-moderate C. difficile infection at a dose of 200 mg orally every 12 hours. Limited early results from the Phase 3 trial showed favorable outcomes for fidaxomicin when compared to oral vancomycin. Overall, fidaxomicin has been well tolerated to date.. The activity of fidaxomicin and limited clinical data suggest that it may have a future role in the treatment of mild-to-moderate C. difficile infection. The complete pharmacokinetic/pharmacodynamic profile, safety, and place in therapy have yet to be determined as trials comparing this agent to vancomycin are forthcoming.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Glycosides; Humans; Microbial Sensitivity Tests; Randomized Controlled Trials as Topic; Treatment Outcome; Vancomycin

During a 10-day treatment for Clostridium difficile infection, OPT-80 and vancomycin were comparably effective in reducing C. difficile counts. Bacteroides fragilis group counts appeared unaffected with increasing dosages of OPT-80, whereas vancomycin was markedly suppressive. Retention of components of the normal microflora might lower the risk of recurrent disease.

Topics: Anti-Bacterial Agents; Bacteroides; Clostridioides difficile; Clostridium Infections; Dose-Response Relationship, Drug; Glycosides; Humans; Vancomycin

OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option for Clostridium difficile infection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity against C. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically

Topics: Adult; Aged; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycosides; Humans; Male; Middle Aged; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Clinical Trials, Phase III as Topic; Clostridioides difficile; Clostridium Infections; Glycosides; Humans; Recurrence

Clostridium difficile remains the major cause of nosocomial diarrhea. Reports on impaired susceptibility of C. difficile to metronidazole and vancomycin and frequent relapses of patients after therapy necessitate the search for new substances. With this study, the activity of OPT-80, a new macrocycle, against 207 C. difficile strains and against other obligately anaerobic bacteria was tested. OPT-80 showed high in vitro activity against all C. difficile strains tested.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Clostridioides difficile; Clostridium Infections; Culture Media; Glycosides; Humans; Microbial Sensitivity Tests