title: 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.affiliation: Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. francesco.scaglione@unimi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Scaglione
authors.forename: Silvana
authors.initials: S
authors.lastname: Dugnani
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucini
authors.forename: Marilou
authors.initials: M
authors.lastname: Pannacci
authors.forename: Luca
authors.initials: L
authors.lastname: Paraboni
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D002722:Chlorobenzenes; D015169:Colony Count, Microbial; D003408:Cresols / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007558:Italy; D008168:Lung / Q000187:drug effects / Q000382:microbiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D013047:Specific Pathogen-Free Organisms; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D002722:Chlorobenzenes; D003408:Cresols; C018874:clofoctol