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Cadazolid
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
Cadazolid (formerly ACT-179811) is a nonabsorbable, fluoroquinolone-oxazolidinone class antibiotic that inhibits bacterial protein synthesis. The substance is moderately lipophilic (log D = 1.2), acidic (pKa = 6.0), and poorly soluble in aqueous solution (150 ng/ml). Its chemical structure is formally [(R)-1-cyclopropyl-6-fluoro-7-{4-[2-fluoro-4-(5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-phenoxymethyl]-4-hydroxy-piperidin-1-yl}-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid], and the molecular formula is C29H29N3O8F2 (Baldoni et al, 2014) (Figure 74.1).
Investigational drug therapies currently in early-stage clinical development for the treatment of clostridioides (clostridium) difficile infection
Published in Expert Opinion on Investigational Drugs, 2019
Mai-Chi N. Tran, Ravina Kullar, Ellie J. C. Goldstein
We previously noted the failure of two promising agents (surotomycin and cadazolid) due to a variety of methodological problems which is hopefully overcome by better trial design for these newer agents. The ultimate goal is to have a variety of effective approaches in the treatment of CDI and the prevention of relapse. The need for a variety of approaches is congruent with the current trend for personalized medicine. It is of import that these new agents offer a variety of approaches from fecal transplant, to enzymatic inactivation to molecules that work using different mechanisms of action. Since the clinical problem of CDI is ubiquitous and urgent, their potential to decrease disease burden and improve therapeutic outcome is equally great. Of note, we covered only drugs and did not review monoclonal antibodies or other new potential biologics that are under development. It is also possible that a bundle approach may be required to overcome the worldwide burden of CDI.
Emerging drugs for the treatment of clostridium difficile
Published in Expert Opinion on Emerging Drugs, 2019
Giovanni Cammarota, Antonella Gallo, Gianluca Ianiro, Massimo Montalto
Phase-III studies are ongoing for cadazolid and results are still not available. Cadazolid, developed by Actelion, is a novel oxazolidinone, with a potent antimicrobial activity against C. difficile and spore formation in vitro, although the exact mechanism of action is not yet fully elucidated [54]. A phase-II study [58] showed lower recurrence rates and higher sustained clinical response in CDI patients when treated with cadazolid (ad doses of 250, 500 or 1,000 mg twice daily) vs. vancomycin treatment (at doses of 125 mg four times daily). Results were independently from different dosages of cadazolid.
Clinical review of Clostridium difficile infection: an update on treatment and prevention
Published in Expert Opinion on Pharmacotherapy, 2018
Lindsay M. Daniels, Wesley D. Kufel
Cadazolid is a poorly absorbed oxazolidinone antibiotic that works by inhibiting bacterial protein synthesis. Two phase 3 studies (NCT01983683 and NCT01987895) compared the safety and efficacy of cadazolid to vancomycin. These trials evaluated non-inferiority for clinical cure as the primary outcome and superiority for sustained cure as the secondary outcome. Results for these trials are currently available on clinicaltrials.gov. In one of these trials (NCT01983683), cadazolid did not meet criteria for non-inferiority for the primary end point or superiority for the secondary end point. Currently, development for cadazolid has been discontinued.