Notwithstanding the limitations of the study sample size, there was no evidence that increasing the cadazolid dosage above 250 mg BID improved efficacy. In the present study, the most frequent PCR ribotype and restriction endonuclease analysis (REA) group were 027 and BI, respectively. Fecal cadazolid concentrations for all dosages of cadazolid were several thousandfold higher than the C. difficile MIC, and the baseline and postbaseline cadazolid MICs were low (≤0.5 mg/liter), including those for the epidemic strains. In addition, minimal impacts on the intestinal microflora were observed at all dosages of cadazolid.
|Cell lines||C. difficile|
|Preparation method||Experiments to assess the effects of cadazolid and comparator antibiotics on C. difficile toxin formation were done by determination of toxin A and B concentrations in stationary-phase cultures of toxigenic C. difficile|
|Concentrations||0.3% (vol/vol) DMSO|
|Incubation time||24 h|
|Animal models||Hamster model of CDAD|
|Formulation||0.5% [wt/wt] methylcellulose containing 0.05% [wt/vol] Tween 80|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection.
Louie T, et al. Antimicrob Agents Chemother. 2015 Oct;59(10):6266-73. PMID: 26248357.
In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.
Locher HH, et al. Antimicrob Agents Chemother. 2014;58(2):892-900. PMID: 24277020.
Dithiothreitol (DTT) is the common name for a small-molecule redox reagent known as Cleland's reagent; as a reducing or "deprotecting" agent for thiolated DNA.
SAR7334 is a novel, highly potent and bioavailable inhibitor of TRPC6 channels.
FICZ is a potent aryl hydrogen receptor (AhR) agonist.
NAD+ is a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage.
STING-Inducer-1 (ML RR-S2 CDA) is an inducer of STING (stimulator of interferon genes).
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