Antibiotic concentrations in hepatic interstitial and wound fluid

Area of Science:

• Pharmacology and Toxicology
• Veterinary Medicine
• Hepatobiliary System

Background:

• Antimicrobial drug distribution is crucial for treating infections, particularly in organs like the liver.
• Understanding how antibiotics distribute between serum, bile, and liver tissue is essential for effective therapy.
• Previous assumptions about high hepatic parenchymal concentrations based on bile excretion needed investigation.

Purpose of the Study:

• To investigate the biliary and hepatic interstitial fluid excretion of common antibiotics in a canine model.
• To compare antibiotic concentrations in bile, hepatic interstitial fluid, and soft tissues.
• To inform antimicrobial selection strategies for hepatic parenchymal infections and obstructive cholecystitis.

Main Methods:

• Utilized tissue-implanted capsules in dogs to measure drug concentrations.
• Administered and measured cephalothin, cefazolin, ampicillin, and tetracycline.
• Analyzed drug levels in serum, bile, hepatic interstitial fluid, and other soft tissues.

Main Results:

• Cephalothin, cefazolin, ampicillin, and tetracycline were excreted into bile at concentrations exceeding serum levels.
• Hepatic interstitial fluid concentrations were similar to those in other soft tissues, not elevated.
• Bile concentration does not correlate with high hepatic parenchymal drug levels.

Conclusions:

• Antibiotics concentrated in bile do not guarantee high concentrations within the liver parenchyma.
• Antimicrobial choice for liver infections should prioritize pathogen susceptibility over bile excretion rates.
• This finding impacts treatment protocols for hepatic parenchymal infections and obstructive cholecystitis.