Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep.
Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75×MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 μg/mL or "shallow" infections caused by bacteria with MICs<0.1 μg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 μg/mL.
Delis
G A
GA
Laboratory of Pharmacology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.
Koutsoviti-Papadopoulou
M
M
Siarkou
V I
VI
Kounenis
G
G
Batzias
G C
GC
D000658:Amoxicillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D016978:Mannheimia haemolytica / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D010326:Pasteurella Infections / Q000188:drug therapy / Q000662:veterinary*; D016979:Pasteurella multocida / Q000187:drug effects*; D016871:Pasteurellaceae Infections / Q000188:drug therapy / Q000662:veterinary*; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000658:Amoxicillin