Cholecystectomy during ceftriaxone therapy. A translational study with a new rabbit model

Area of Science:

• Gastroenterology
• Pharmacology
• Pathology

Background:

• Ceftriaxone is a widely used third-generation cephalosporin antibiotic.
• Gallbladder disease, including cholecystitis and gallstones, affects a significant portion of the population.
• The potential link between antibiotic use and gallbladder complications requires further investigation.

Purpose of the Study:

• To investigate the incidence of biliary microlithiasis and acute cholecystitis in a rabbit model treated with intravenous ceftriaxone.
• To evaluate the pathological and biochemical changes associated with ceftriaxone administration in the gallbladder.

Main Methods:

• New Zealand rabbits received intravenous ceftriaxone or saline for 21 days.
• Gallbladder ultrasound, histopathology, immunohistochemistry (PCNA, pro-caspase-3, CD68), liver enzyme analysis, and bile chromatography were performed.
• Key biomarkers and cellular changes were assessed to understand the mechanism of action.

Main Results:

• All rabbits treated with ceftriaxone developed acute cholecystitis and biliary microlithiasis.
• Elevated pro-caspase-3, gamma-glutamyl transpeptidase, PCNA expression, and CD68-positive cells were observed in the ceftriaxone group.
• Increased cholesterol and lecithin in bile, with ceftriaxone detected in microlithiasis, indicated a lithogenic bile environment.

Conclusions:

• Intravenous ceftriaxone at therapeutic doses significantly increases the risk of lithogenic bile formation.
• Ceftriaxone administration leads to a high incidence of acute lithiasic cholecystitis in this rabbit model.
• These findings highlight a potential adverse effect of ceftriaxone on gallbladder health.