Can ampicillin and ceftriaxone (antibiotics) worsen impaired renal function?

From the Guidelines

Ampicillin and ceftriaxone are not likely to worsen renal function, and in fact, the combination of ampicillin and ceftriaxone has been shown to have a lower risk of nephrotoxicity compared to ampicillin and gentamicin. According to a study published in Circulation in 2015 1, none of the patients in either study developed nephrotoxicity with ampicillin-ceftriaxone therapy, whereas 20 of 87 (23%) ampicillin-gentamicin–treated patients developed nephrotoxicity. This suggests that the combination of ampicillin and ceftriaxone may be a safer option for patients with impaired renal function. Some key points to consider when using these antibiotics in patients with renal impairment include:

• The lack of need for measuring serum concentrations with ampicillin and ceftriaxone, which can simplify treatment and reduce the risk of nephrotoxicity 1
• The potential for hypersensitivity reactions to either ampicillin or ceftriaxone, which may require discontinuation of both drugs and substitution with an alternative regimen 1
• The importance of individualizing treatment and monitoring renal function closely in patients with pre-existing kidney disease, as the risk of nephrotoxicity can vary depending on the specific clinical context 1.

From the FDA Drug Label

Patients with Renal or Hepatic Impairment Ceftriaxone is excreted via both biliary and renal excretion (see CLINICAL PHARMACOLOGY). Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of ceftriaxone are administered Urolithiasis and Post-Renal Acute Renal Failure Ceftriaxone-calcium precipitates in the urinary tract have been observed in patients receiving ceftriaxone and may be detected as sonographic abnormalities. In patients with renal function impairment, ampicillin-class antibiotics can be removed by hemodialysis but not by peritoneal dialysis.

Ampicillin and Ceftriaxone can potentially worsen renal function, especially in patients with pre-existing renal impairment.

• Ceftriaxone may cause urolithiasis and post-renal acute renal failure due to ceftriaxone-calcium precipitates in the urinary tract.
• Ampicillin can accumulate in patients with renal function impairment, as it can be removed by hemodialysis but not by peritoneal dialysis. It is essential to exercise caution and monitor renal function closely when administering these antibiotics to patients with impaired renal function 2, 2, 3.

From the Research

Renal Function and Antibiotics

• The use of antibiotics such as ampicillin and ceftriaxone in patients with impaired renal function can be complex, with potential effects on renal function.
• Studies have shown that ceftriaxone is primarily eliminated through nonrenal mechanisms, which reduces the need for dose adjustments in patients with mild to moderate renal impairment 4.
• However, in patients with severe renal impairment, the half-life of ceftriaxone may be increased, potentially leading to drug accumulation 5.

Ampicillin and Renal Insufficiency

• Ampicillin, on the other hand, relies on active renal tubular secretion for urinary excretion, which can be impaired in patients with renal insufficiency 6.
• This reduction in renal tubular secretion can lead to decreased urinary excretion of ampicillin, potentially resulting in increased drug concentrations and toxicity.
• Dosage adjustment based on creatinine clearance may not be sufficient for patients receiving ampicillin, and a more comprehensive approach considering both glomerular and renal tubular functions may be necessary 6.

Ceftriaxone-Related Renal Failure

• There have been reports of ceftriaxone-related hemolysis and acute renal failure, particularly in patients receiving combination therapy with other antibiotics such as ampicillin-sulbactam 7.
• In these cases, the development of immune hemolytic anemia and acute interstitial nephritis can lead to severe renal insufficiency, requiring prompt medical attention and potentially dialysis.

Dose Reduction and Renal Function

• The effectiveness of dose reduction in renally cleared antibiotics, including ampicillin and ceftriaxone, in patients with impaired renal function is still a topic of debate 8.
• While some studies suggest that reduced doses may be adequate for achieving sufficient antibiotic drug exposure, others highlight the lack of good-quality evidence to support specific dose reduction recommendations.