Pharmacokinetic/Pharmacodynamic Evaluation of Solithromycin Against Streptococcus pneumoniae Using Data from a Neutropenic Murine-Lung Infection Model.

Pharmacokinetic/Pharmacodynamic Evaluation of Solithromycin Against Streptococcus pneumoniae Using Data from a Neutropenic Murine-Lung Infection Model. Antimicrob Agents Chemother. 2019 Jun 10;: Authors: Okusanya OO, Forrest A, Bhavnani SM, Fernandes P, Ambrose PG, Andes DR Abstract Solithromycin (CEM-101) is a novel fluoroketolide antimicrobial agent with activity against typical and atypical pathogens associated with community-acquired bacterial pneumonia. Using a neutropenic murine-lung infection model, the objectives of this study were to identify the pharmacokinetic/pharmacodynamic (PK/PD) index most closely associated with efficacy and the magnitude of such indices necessary for solithromycin efficacy against Streptococcus pneumoniae Plasma and epithelial lining fluid (ELF) samples for pharmacokinetics (PK) were collected serially over 24 hours from healthy mice administered single doses of solithromycin (0.625 to 40 mg/kg). Neutropenic CD-1 mice infected with 108 colony forming units (CFU) of one of five S. pneumoniae isolates were administered solithromycin (0.156 to 160 mg/kg/day) via oral gavage. Doses were administered in a fractionated manner for mice infected with one isolate while mice infected with the remaining four isolates received solithromycin as either a q6h or q12h regimen. A three-compartment model best described solithromycin PK in the plasma and ELF (r2 = 0.935 and 0.831, respectively). The ratio of total-dru...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research