Ceftriaxone is a third-generation cephalosporin antibiotic used to treat various bacterial infections. It works by inhibiting bacterial cell wall synthesis. The drug is eliminated through both the kidneys (33% to 67%) and the bile (remainder), which explains its effects on the kidneys and biliary system.
Gallbladder: Biliary Pseudolithiasis
Ceftriaxone is known to affect the gallbladder. It is excreted into the bile at high concentrations and can bind with calcium ions, forming an insoluble precipitate. This can lead to gallbladder sludge or stones, called biliary pseudolithiasis.
This sludge formation occurs in 3% to 46% of patients, with potentially higher incidence in children. Risk factors include high doses, long treatment duration, dehydration, and fasting. While often asymptomatic, it can cause biliary colic and, rarely, cholecystitis or pancreatitis. The condition is usually reversible upon stopping the drug.
Kidneys: Nephrotoxicity and Stone Formation
The kidneys are another main organ involved in ceftriaxone elimination and are at risk. Ceftriaxone-calcium salts can precipitate in urine, forming crystals and stones (nephrolithiasis) that may obstruct the urinary tract. This can cause flank pain and blood in the urine. Risk is higher in children, dehydrated, or immobilized patients. Severe obstruction can lead to post-renal acute renal failure. Crystals can also cause kidney injury through inflammation and oxidative stress. Renal failure is a rare but recognized risk, especially in children.
Liver: Hepatotoxicity
Ceftriaxone's effect on the liver is less common than gallbladder issues but can occur.
Cholestatic Hepatitis
A rare, immunoallergic reaction can cause cholestatic hepatitis, reducing bile flow. Symptoms like jaundice, abdominal pain, and nausea may appear weeks into therapy and are typically associated with fever, rash, and elevated liver enzymes. This drug-induced liver injury is usually mild and resolves after stopping the drug.
Other Organ System Effects
- Hematologic System: Changes in blood counts, including eosinophilia and leukopenia, can occur. Drug-induced hemolytic anemia is a rare but serious side effect.
- Gastrointestinal Tract: Like many antibiotics, it can cause diarrhea and, rarely, Clostridioides difficile-associated diarrhea.
- Central Nervous System: Neurotoxicity, including encephalopathy and seizures, is rare and more likely in patients with severe renal disease where the drug accumulates.
Organ-Specific Effects Comparison
| Organ | Mechanism of Effect | Common Manifestation | Typical Outcome |
|---|---|---|---|
| Gallbladder | Precipitation with calcium ions in bile | Biliary pseudolithiasis (sludge/stones) | Usually asymptomatic and reversible upon drug discontinuation |
| Kidneys | Precipitation with calcium ions in urine, leading to crystals and inflammation | Nephrolithiasis (kidney stones), ureteral obstruction, increased creatinine | Reversible upon discontinuation, but can lead to acute renal failure if severe |
| Liver | 1. Biliary excretion leading to sludge 2. Rare immunoallergic reaction |
1. Cholestasis secondary to sludge 2. Drug-induced cholestatic hepatitis (elevated enzymes) |
Generally mild and self-limiting after stopping the drug |
Conclusion
Ceftriaxone primarily affects the gallbladder and kidneys due to its excretion pathways, causing reversible calcium precipitates that can lead to sludge or stones. While often manageable, these can lead to complications. A less common effect is direct inflammatory injury to the liver. Awareness of these effects is crucial for patient monitoring, especially in vulnerable groups.
For further reading on ceftriaxone's hepatic effects, you can visit the NCBI LiverTox Database.
