In vitro and in vivo pharmacokinetic/pharmacodynamic activity of clofoctol.

Abstract

The aim of the study was to examine the In vitro susceptibility of clinical isolates of respiratory pathogens to clofoctol compared with amoxicillin and erythromycin, and to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationships of clofoctol using a murine pneumonia infection model. Strains clinically isolated from patients between 2005 and 2009 were used to examine susceptibility: penicillin-susceptible Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, Streptococcus pyogenes, methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and Haemophilus influenzae. The In vitro activity of clofoctol against clinical isolates has essentially remained unchanged over recent years. The MIC₅₀ and MIC₉₀ of clofoctol against penicillin-resistant S. pneumoniae are lower than that of amoxicillin and erythromycin. The area under curve/minimum inhibitory concentration (AUC/MIC) ratio is the PK/PD parameter that best correlates with in vivo clofoctol efficacy; the value of AUC/MIC required to achieve the maximum effect in this study was 75.5.

• Authors: Francesco Scaglione, Silvana Dugnani, Valeria Lucini, Marilou Pannacci, Luca Paraboni
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 24 Issue 4 Pg. 201-6 (Aug 2012) ISSN: 1973-9478 [Electronic] England
• PMID: 23040683 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Chlorobenzenes
• Cresols
• clofoctol

Topics

• Animals
• Anti-Bacterial Agents (blood, pharmacokinetics, pharmacology, therapeutic use)
• Chlorobenzenes
• Colony Count, Microbial
• Cresols (blood, pharmacokinetics, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Haemophilus influenzae (drug effects, isolation & purification)
• Humans
• Italy
• Lung (drug effects, microbiology)
• Methicillin-Resistant Staphylococcus aureus (drug effects, isolation & purification)
• Mice
• Mice, Inbred BALB C
• Microbial Sensitivity Tests
• Penicillin Resistance
• Pneumonia, Pneumococcal (blood, drug therapy, microbiology)
• Specific Pathogen-Free Organisms
• Staphylococcus aureus (drug effects, isolation & purification)
• Streptococcus pneumoniae (drug effects, isolation & purification, metabolism)
• Streptococcus pyogenes (drug effects, isolation & purification)