Unknown

Dataset Information

0

In Vivo Pharmacokinetic and Pharmacodynamic Profiles of Antofloxacin against Klebsiella pneumoniae in a Neutropenic Murine Lung Infection Model.


ABSTRACT: Antofloxacin is a novel broad-spectrum fluoroquinolone under development for the treatment of infections caused by a diverse group of bacterial species. We explored the pharmacodynamic (PD) profile and targets of antofloxacin against seven Klebsiella pneumoniae isolates by using a neutropenic murine lung infection model. Plasma and bronchopulmonary pharmacokinetic (PK) studies were conducted at single subcutaneous doses of 2.5, 10, 40, and 160 mg/kg of body weight. Mice were infected intratracheally with K. pneumoniae and treated using 2-fold-increasing total doses of antofloxacin ranging from 2.5 to 160 mg/kg/24 h administered in 1, 2, 3, or 4 doses. The Emax Hill equation was used to model the dose-response data. Antofloxacin could penetrate the lung epithelial lining fluid (ELF) with pharmacokinetics similar to those in plasma with linear elimination half-lives over the dose range. All study strains showed a 3-log10 or greater reduction in bacterial burden and prolonged postantibiotic effects (PAEs) ranging from 3.2 to 5.3 h. Dose fractionation response curves were steep, and the free-drug area under the concentration-time curve over 24 h (AUC0-24)/MIC ratio was the PD index most closely linked to efficacy (R2 = 0.96). The mean free-drug AUC0-24/MIC ratios required to achieve net bacterial stasis, a 1-log10 kill, and a 2-log10 kill for each isolate were 52.6, 89.9, and 164.9, respectively. When integrated with human PK data, these PD targets could provide a framework for further optimization of dosing regimens. This could make antofloxacin an attractive option for the treatment of respiratory tract infections involving K. pneumoniae.

SUBMITTER: Zhou YF 

PROVIDER: S-EPMC5404557 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

<i>In Vivo</i> Pharmacokinetic and Pharmacodynamic Profiles of Antofloxacin against Klebsiella pneumoniae in a Neutropenic Murine Lung Infection Model.

Zhou Yu-Feng YF   Tao Meng-Ting MT   Huo Wei W   Liao Xiao-Ping XP   Sun Jian J   Liu Ya-Hong YH  

Antimicrobial agents and chemotherapy 20170424 5


Antofloxacin is a novel broad-spectrum fluoroquinolone under development for the treatment of infections caused by a diverse group of bacterial species. We explored the pharmacodynamic (PD) profile and targets of antofloxacin against seven <i>Klebsiella pneumoniae</i> isolates by using a neutropenic murine lung infection model. Plasma and bronchopulmonary pharmacokinetic (PK) studies were conducted at single subcutaneous doses of 2.5, 10, 40, and 160 mg/kg of body weight. Mice were infected intr  ...[more]

Similar Datasets

| S-EPMC6658793 | biostudies-literature
| S-EPMC9244213 | biostudies-literature
| S-EPMC5937563 | biostudies-literature
| S-EPMC5444146 | biostudies-literature
| S-EPMC8632807 | biostudies-literature
| S-EPMC5740385 | biostudies-literature
| S-EPMC6784242 | biostudies-literature
2023-09-14 | GSE237490 | GEO
| S-EPMC5278741 | biostudies-literature
| S-EPMC3910830 | biostudies-other