Discovery and development of surotomycin for the treatment of Clostridium difficile

Abstract

The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6-25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin.

Advances in the diagnosis and treatment of Clostridium difficile infections

“…The patients treated with cadazolid had higher sustained clinical response rates than those treated with vancomycin (46.7–60.0% vs. 33.3%) 56 . A following study noted that cadazolid was more effective against the C. difficile strains isolated from the patients in this phase 2 study because the minimum inhibitory concentrations (MICs) for cadazolid were lower than those of vancomycin, linezolid, and moxifloxacin 57 . Cadazolid is now being evaluated in phase 3 clinical trials 52 ; the data from these studies are not yet available.…”

Synthetic surfactin analogues have improved anti-PEDV properties

“…Fatty acid chain length is critical to the antimicrobial effect of synthetic polymyxin analogues [7], while the specific antimicrobial spectrum of these analogues depends the amino acids in the lipopeptide [8]. Additionally, in synthetic daptomycin analogues, the introduction of aromatic groups in the fatty acid moiety also affects antibacterial activity [9]. In this study, a series of similar lipopeptides were designed and synthesized using surfactin as a template.…”

Evaluating the Effects of Surotomycin Treatment on Clostridium difficile Toxin A and B Production, Immune Response, and Morphological Changes

“…The increased incidence and severity of CDI have prompted the development of new compounds with activity against C. difficile. Surotomycin (formerly CB-183,315) is a novel narrow-spectrum, minimally absorbed antibiotic that is currently being evaluated for the treatment of CDI (5). Surotomycin affects the cell wall integrity of C. difficile by dissipating the membrane potential, thereby killing the bacteria (6).…”