oritavancin and Enterocolitis--Pseudomembranous

Clostridium difficile infection (CDI) is associated with consumption of antibiotics which disrupt the normal microbial flora of the gut, allowing C. difficile to establish itself and produce disease. Currently, only vancomycin or metronidazole are recommended for treatment and many patients suffer from relapse on infection. Hence, there is a need for new treatment options.. This review evaluates five agents in development where the focus is on treatment of CDI.. This review gives up-to-date information on fidaxomicin, REP3123, oritavancin, NVB302 and nitazoxanide and their likelihood of being licensed for the treatment of CDI.. One agent, fidaxomicin, has undergone Phase III clinical trials which show it to be a promising new agent for the treatment of CDI with a low rate of relapse. Nitazoxanide is licensed for the treatment of parasitic intestinal infections but is not licensed for CDI. However, in small scale clinical trials it has been shown to have activity comparable to that of vancomycin and metronidazole. The other agents are all at early stages of development and clinical trials to evaluate their therapeutic potential for CDI have not yet been undertaken.

Topics: Aminoglycosides; Anti-Bacterial Agents; Benzopyrans; Clostridioides difficile; Enterocolitis, Pseudomembranous; Fidaxomicin; Glycopeptides; Humans; Lipoglycopeptides; Nitro Compounds; Thiazoles; Thiophenes

Clostridium difficile infection is a nosocomial disease of increasing importance. First-line treatment is limited to metronidazole or vancomycin. Oritavancin is a lipoglycopeptide with activity against Gram-positive bacteria, including drug-resistant pathogens. MICs of oritavancin, metronidazole and vancomycin for genotypically distinct C. difficile strains, including epidemic C. difficile PCR ribotypes 001 and 027, were determined by agar incorporation and broth macrodilution methods. In agar incorporation methods, the impact of supplements on oritavancin MICs was tested to address oritavancin binding to surfaces.. Thirty-three genotypically distinct C. difficile strains were identified by PCR ribotyping. Wilkins Chalgren agar incorporation plates containing oritavancin, metronidazole and vancomycin were prepared with and without 0.002% polysorbate-80 (P80) and lysed horse blood (2%). Broth macrodilution MICs of oritavancin, metronidazole and vancomycin were determined in Brucella broth. Inoculated agar incorporation plates and broth macrodilution tubes were cultured anaerobically at 37 degrees C for 48 h.. Broth macrodilution MICs were lower than agar incorporation MICs for oritavancin, but not for metronidazole and vancomycin. Oritavancin broth macrodilution MIC(90)s were 2- to 4-fold lower than the corresponding agar incorporation MIC(90)s, while geometric mean MICs were >5-fold lower. Oritavancin broth macrodilution MIC(90)s were approximately 2- and 5-fold lower than those for metronidazole and vancomycin. Metronidazole was the most active antimicrobial agent against C. difficile using agar incorporation methods. Oritavancin agar incorporation MIC(90)s were unaffected by 0.002% P80 and/or 2% lysed horse blood.. Oritavancin was at least 4-fold more potent than vancomycin against the majority (25/33) of C. difficile strains tested by broth macrodilution. Oritavancin activity may be underestimated by agar incorporation methods, regardless of the use of P80 or lysed horse blood.

Topics: Anti-Bacterial Agents; Clostridioides difficile; Culture Media; DNA Fingerprinting; Enterocolitis, Pseudomembranous; Genotype; Glycopeptides; Humans; Lipoglycopeptides; Metronidazole; Microbial Sensitivity Tests; Ribotyping; Vancomycin

To compare the efficacy of oritavancin and vancomycin in the treatment of Clostridium difficile infection (CDI) using an in vitro human gut model.. We induced CDI by instilling clindamycin into an in vitro gut model primed with pooled human faeces and C. difficile ribotype 027 spores. Oritavancin and vancomycin were instilled in separate experiments at levels equivalent to those expected in the faeces (vancomycin) of patients or levels limited by the solubility of the drug (oritavancin).. Clindamycin exposure elicited C. difficile proliferation and high-level cytotoxin production in both experiments. Vancomycin instillation reduced vegetative C. difficile numbers within 1 day but did not affect the numbers of C. difficile spores. Oritavancin instillation markedly reduced C. difficile vegetative numbers and spores to below the limits of detection within 2 days. Cytotoxin titres in both experiments declined to the limits of detection after instillation with oritavancin or vancomycin, but did so more quickly (within 5 days) in the vancomycin experiment. Cessation of vancomycin instillation was associated with further C. difficile proliferation and high-level cytotoxin production. Conversely, toxin recrudescence was not observed following cessation of oritavancin.. Both oritavancin and vancomycin were effective in treating clindamycin-induced CDI in a human gut model, but only oritavancin appeared active against spore forms of C. difficile. Furthermore, recurrence of high-level cytotoxin production was observed following vancomycin instillation but not oritavancin. Oritavancin therapy may be more effective in treating CDI than vancomycin, possibly because it may prevent recrudescence of C. difficile spores.

Topics: Anti-Bacterial Agents; Bacterial Toxins; Clindamycin; Clostridioides difficile; Colony Count, Microbial; DNA, Bacterial; Enterocolitis, Pseudomembranous; Glycopeptides; Humans; In Vitro Techniques; Lipoglycopeptides; Microbial Viability; Polymerase Chain Reaction; Ribotyping; Spores, Bacterial; Vancomycin