surotomycin (MK-4261) / Merck (MSD) - LARVOL DELTA

Fighting against Clostridioides difficile infection: Current medications. (PubMed, Int J Antimicrob Agents) - "Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and fecal microbiota transplantation (FMT) for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g., teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g., Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g., vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g., Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarizes current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation."

Journal • Review • Infectious Disease • Transplantation

Microbiome-preserving antibiotics for the treatment of Clostridioides difficile infection: a systematic review and meta-analysis. (PubMed, Tech Coloproctol) - "Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics."

Clinical • Journal • Retrospective data • Review • Infectious Disease

HexSDF Is Required for Synthesis of a Novel Glycolipid That Mediates Daptomycin and Bacitracin Resistance in C. difficile. (PubMed, mBio) - "There has been recent interest in using a daptomycin analog, surotomycin, to treat C. difficile infections. Little is understood about C. difficile membrane lipids, but a unique glycolipid, HNHDRG, has been previously identified in C. difficile and, currently, has not been identified in other organisms. Here, we show that HexSDF and HexRK are required for synthesis of HNHDRG and that production of HNHDRG impacts resistance to daptomycin and bacitracin."

Journal • Infectious Disease

Surotomycin (a novel cyclic lipopeptide) vs Vancomycin for treatment of Clostridioides difficile infection: A systematic review and Meta-analysis. (PubMed, Curr Clin Pharmacol) - "Surotomycin is non-inferior to vancomycin and offers a promising alternative for the treatment and prevention of C. diff infection. ."

Journal • Retrospective data • Review

Characterization of Clostridioides difficile isolates recovered from two Phase 3 surotomycin treatment trials by restriction endonuclease analysis, PCR ribotyping and antimicrobial susceptibilities. (PubMed, J Antimicrob Chemother) - P3 | "A wide variation in C. difficile strains, both within and across different geographical regions, was documented by both REA and ribotyping, which showed overall good correlation."

Journal • P3 data

Analysis of Clostridium difficile biofilms: imaging and antimicrobial treatment. (PubMed, J Antimicrob Chemother) - "In this study, we evaluated and compared the efficacy of four antibiotics (fidaxomicin, surotomycin, vancomycin and metronidazole) in penetrating C. difficile biofilms and killing vegetative cells. After 24 h of treatment, SEM demonstrated that both fidaxomicin and surotomycin disrupted the biofilm structure, while metronidazole had no observable effect. Fidaxomicin is effective in disrupting C. difficile biofilms, killing vegetative cells and decreasing spore counts."

Journal • Biosimilar • Immunology

Enteric microbiome profiles during a randomized Phase 2 clinical trial of surotomycin versus vancomycin for the treatment of Clostridium difficile infection. (PubMed, J Antimicrob Chemother) - "In this Phase 2 trial substudy, compared with vancomycin 125 mg four times daily, surotomycin 250 mg twice daily is as active in vivo against C. difficile , but was more sparing of microbiota. Surotomycin is no longer in development due to failed Phase 3 efficacy results."

Journal • Biosimilar • Immunology

Cadazolid for the treatment of Clostridium difficile. (PubMed) - Expert Opin Investig Drugs - "Clinical therapeutic outcomes are compared between cadazolid, fidaxomicin, and surotomycin. Expert opinion: Preclinical and early clinical studies demonstrated that cadazolid has unique properties that will likely be valuable to treat CDI and reduce recurrent infection. With compelling phase II clinical results, results from the ongoing phase III trial will better define the role of cadazolid for treating CDI in the future."

Journal • Biosimilar • Immunology

Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea (clinicaltrials.gov) - P3; N=608; Completed; Sponsor: Cubist Pharmaceuticals; Active, not recruiting -> Completed

Trial completion • Biosimilar • Immunology

Study of CB-183,315 in Patients With Clostridium Difficile Associated Diarrhea (clinicaltrials.gov) - P3; N=608; Active, not recruiting; Sponsor: Cubist Pharmaceuticals; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Immunology

The perils of PCR-based diagnosis of Clostridioides difficile infections: painful lessons from clinical trials. (PubMed, Anaerobe) - "Bezlotoxumab, a human monoclonal antibody neutralizing toxin B, was found to be protective against recurrent CDI (rCDI) in clinical trials...Surotomycin, an oral lipopeptide antibiotic, was found to be non-inferior to vancomycin in phase 2 study, but development was discontinued after unfavourable phase 3 results in which the majority of CDI were diagnosed by PCR...We highlighted the perils of using PCR alone in studies involving different aspects of C. difficile clinical research, including immunotherapies, microbiome-based therapies, treatments, and vaccines. The importance of designing C. difficile clinical trials with careful consideration to the diagnostic testing method cannot be overemphasized."

Clinical • Journal

Multidrug resistance in anaerobes. (PubMed, Future Microbiol) - "MDR was present in >1/2 of Clostridioides difficile isolates, most often in epidemic/hypervirulent strains and unusually high metronidazole or vancomycin resistance has been reported in single studies. Resistance in the anaerobes tends to be less predictable and anaerobic microbiology is required in more laboratories. New hopes may be new antibiotics such as eravacycline, cadazolid, surotomycin, ridinilazol or C. difficile toxoid vaccines; however, more efforts are needed to track the MDR in anaerobes."

Journal

Treatment of acute and recurrent Clostridium difficile infections : What is new? (PubMed, Internist (Berl)) - "Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed."

Journal • Review

Emerging drugs for the treatment of Clostridium difficile. (PubMed, Expert Opin Emerg Drugs) - "...Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C difficile infection...Expert opinion We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population."

Journal • Review