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Surotomycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Surotomycin (CB-183,315; MK-4261) belongs to the lipopeptides and is a semisynthetic derivate cyclic tail analogue of daptomycin (see Chapter 45, Daptomycin) designed specifically to improve the activity against Clostridium difficile (Yin et al., 2015). It has the same peptide sequence as daptomycin but has an aromatic ring containing an unsaturated lipid tail, (E)-3-(4-pentylphenyl) but-2-enoic acid tail. The molecular formula for surotomycin is C77H101N17O26 with a corresponding molecular weight of 1680.7 g/mol (PubChem, 2016). The molecular structure of surotomycin is depicted in Figure 50.1. Its mechanism of action is similar to that of daptomycin, cell membrane depolarization leading ultimately to cell death (Mascio et al., 2012). It was developed by Cubist Pharmaceuticals but is now owned by Merck & Co. (North Wales, PA).
Emerging drugs for the treatment of clostridium difficile
Published in Expert Opinion on Emerging Drugs, 2019
Giovanni Cammarota, Antonella Gallo, Gianluca Ianiro, Massimo Montalto
Surotomycin (developed by Merck), an oral lipopeptide antibiotic analog of daptomycin, with bactericidal activity against Gram-positive bacteria, was also tested in two parallel double-blinded phase-III randomized clinical trials (RCTs) [56,57]. Both of them were designed to demonstrate non inferiority of surotomycin (at doses of 250 mg twice daily) vs. vancomycin (at dosed of 125 mg four times daily) for resolving CDI, and surotomycin superiority over vancomycin in prevention of recurrence. Results of these two studies were not concordant. Only one of them demonstrated surotomycin non-inferiority vs. vancomycin for primary end point, that was response rate at the end of treatment (day 10). Instead it did not demonstrate superiority to vancomycin for the secondary end point, that was sustained response at 30–40 days after the end of treatment [56]. The other study, performed with the same doses of surotomycin, failed to show non-inferiority of this novel antibiotic over vancomycin [57]. Further studies are necessary to confirm these data.
Interaction of drugs with gut microbiota modulators
Published in Drug Metabolism Reviews, 2023
Antibiotics are frequently used for the treatment of bacterial infections. However, orally administered or bile duct-excreted antibiotics suppress pathogens, as well as significantly fluctuate the composition and quantity of gut microbiota, leading to gut microbiota dysbiosis (Lange et al. 2016; Jang et al. 2018; Angelucci et al. 2019). However, some studies reported that antibiotics alleviated gut microbiota dysbiosis, resulting in the alleviation of psychiatric disorders (Tisdale et al. 1960; Lange et al. 2016). Leclercq et al. reported that oral administration of antibiotics reduced anxiety-like behavior in mice (Leclercq et al. 2017). However, Atli et al. reported that oral administration of amoxicillin caused depression in rats (Atli et al. 2016). Jang et al. also reported that ampicillin caused anxiety, gut microbiota dysbiosis, and colitis in mice (Jang et al. 2018). Ma et al. also reported that ampicillin caused gut microbiota dysbiosis and immune imbalance in mice (Ma et al. 2021). Oral gavage of antibiotics, particularly clindamycin and surotomycin, causes the superinfection overgrowth of Clostridiodes difficile (Finegold 1986; Chilton et al. 2018). The overgrowth of Clostridiodes difficile causes hemorrhagic colitis. Antibiotics directly change the pharmacokinetics and pharmacodynamics of drugs such as metformin and buspirone (Kivistö et al. 1997; Weersma et al. 2020). Moreover, the shift in gut microbiota by antibiotics can fluctuate the gut microbiota-mediated pharmacokinetics of drugs such as aspirin and acetaminophen, and foods by regulating the metabolic enzyme activity and transporter expression (Levy 1981; Lee et al. 2012; Kim et al. 2016).
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
Clostridium difficile (C. difficile) is a Gram-positive spore-forming anaerobic bacterium that causes life-threatening diarrhea, killing 14,000 people annually in the United States alone [80]. About 25% of patients treated with vancomycin, metronidazole, or fidaxomicin have a recurrence of the infection. There are no antibiotics that are effective for multiple recurrences [81]. The only option for patients with multiple recurrent C. difficile is fecal transplantation. Surotomycin, a lipopeptide antibiotic that induces membrane depolarization, is in phase III clinical trials for the treatment of CDI [82].