ArticleAntimicrobial agents and chemotherapy2014
Investigations of the mode of action and resistance development of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2020Guideline
- Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults.The Cochrane database of systematic reviews · 2017Pooled it
- Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection.The Journal of antimicrobial chemotherapy · 2016Trial
- Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.Antimicrobial agents and chemotherapy · 2015Trial
- Artificial Intelligence-Guided Phenotypic Drug Repurposing Against Streptococcus pneumoniae.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antibiotic hybrids: A promising strategy to replenish the pipeline and combat antimicrobial resistance.Journal of microbiology (Seoul, Korea) · 2026Review
- Hybrid Antibiotics Targeting the Bacterial Ribosome.ACS central science · 2025Article
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- Recent advances in fecal microbiota transplantation forFrontiers in microbiomes · 2024Review
- Fighting antibiotic resistance-strategies and (pre)clinical developments to find new antibacterials.EMBO reports · 2023Review
- Bifunctional antibiotic hybrids: A review of clinical candidates.Frontiers in pharmacology · 2023Review
- Article
- Discovery of a Potent Picolinamide Antibacterial Active againstACS infectious diseases · 2020Article
- Multitarget Approaches against Multiresistant Superbugs.ACS infectious diseases · 2020Review
- The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance.Research (Washington, D.C.) · 2020Review
- Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids.Molecules (Basel, Switzerland) · 2019Article
- Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic.Scientific reports · 2019Article
- Unraveling the Molecular Mechanism of Selective Antimicrobial Activity of 2(5International journal of molecular sciences · 2019Article
- Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.Annals of the New York Academy of Sciences · 2019Review
- [Treatment of acute and recurrent Clostridium difficile infections : What is new?]Der Internist · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment of Clostridium difficile-associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development in C. difficile strains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription/translation assays using extracts from different C. difficile strains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally <10(-10) at 2× to 4× the MIC), and in multiple-passage experiments (up to 13 passages) MICs did not significantly increase. Furthermore, no cross-resistance was observed, as cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.
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