Cadazolid

Biological Activity

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.

Protocol

Cell Experiment
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 Experiment
Animal models	Hamster model of CDAD
Formulation	0.5% [wt/wt] methylcellulose containing 0.05% [wt/vol] Tween 80
Dosages	10 mg/kg
Administration	gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

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 K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

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.