Can Cephalosporin (a type of antibiotic) cause impaired renal function?

From the Guidelines

Cephalosporins are not typically associated with significant harm to renal function, and their use is often recommended over potentially nephrotoxic antibiotics, such as aminoglycosides, in certain clinical scenarios. The risk of nephrotoxicity varies among different generations and specific drugs within the cephalosporin class, but they are generally considered safer than other antibiotic options in terms of renal function [ 1 ]. For example, cefotaxime, a third-generation cephalosporin, has been extensively studied in patients with spontaneous bacterial peritonitis (SBP) and has shown high ascitic fluid concentrations during therapy, with infection resolution rates of 77-98% [ 1 ].

• Key factors to consider when evaluating the potential harm of cephalosporins to renal function include:
  • The specific cephalosporin being used, as some may have a higher risk of nephrotoxicity than others
  • The patient's underlying renal function and any pre-existing kidney disease
  • The presence of other nephrotoxic agents or conditions that may increase the risk of renal harm
  • The dosage and duration of cephalosporin therapy, as well as any necessary adjustments based on creatinine clearance
• Regular monitoring of renal function through serum creatinine and estimated glomerular filtration rate is recommended during cephalosporin treatment, especially for high-risk patients or those on longer courses [ 1 ].
• In general, cephalosporins are considered a safer option than aminoglycosides, which have been shown to have a higher risk of nephrotoxicity, particularly in patients with pre-existing kidney disease or those receiving multiple nephrotoxic agents [ 1 ].

From the FDA Drug Label

As with other cephalosporins, anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia have been reported Cephalosporin-Class Adverse Reactions In addition to the adverse reactions listed above that have been observed in patients treated with cefepime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis, and pancytopenia. Increased alkaline phosphatase, BUN, calcium, creatinine, phosphorus, potassium, total bilirubin; decreased calcium*, hematocrit, neutrophils, platelets, WBC

Cephalosporins, including cefepime, may cause renal dysfunction and toxic nephropathy. Key points to consider are:

• Renal dysfunction has been reported for cephalosporin-class antibiotics.
• Toxic nephropathy is also a potential adverse reaction.
• Laboratory changes such as increased BUN and creatinine have been observed. However, it is essential to note that these adverse reactions are not exclusively related to cefepime but are also associated with the cephalosporin class of antibiotics in general 2.

From the Research

Cephalosporin-Induced Nephrotoxicity

• Cephalosporins are known to have a low incidence of relevant nephrotoxicity when used alone, with the most recently developed cephalosporins being remarkable for their effectiveness and safety 3.
• All cephalosporins are thought to be potentially nephrotoxic at high doses, with the usual site of damage being the renal tubule, and interstitial nephritis being less common 3.
• The pathogenesis of nephrotoxicity is thought to be directly dose-related rather than due to hypersensitivity, and it is prudent to consider this when evaluating new cephalosporins and prescribing them, especially in patients with compromised renal function 3.

Specific Cephalosporins and Nephrotoxicity

• Cephaloridine and cephalothin have been implicated in causing nephrotoxicity, both alone and in combination with aminoglycosides, in animal and human data 4, 5.
• Cefazolin has been shown to be nephrotoxic in animals, but not in humans, while ceftazidime has been documented to cause nephrotoxicity, especially in patients with preexisting renal impairment 4.
• Other cephalosporins, such as third-generation cephalosporins, have been reported to have a lower risk of nephrotoxicity, but can still cause renal injury, including nephrolithiasis, immune-mediated hemolytic anemia, or acute interstitial nephropathy 6.

Risk Factors and Prevention

• Pre-existing chronic kidney disease and concomitant use of medication with nephrotoxic potential are general risk factors for antimicrobial-induced acute kidney injury (AKI) 7.
• Prevention and early recognition of AKI are crucial to mitigate AKI and avoid morbidity, and clinicians should be aware of the potential adverse interactions between cephalosporins and other antibiotics, such as aminoglycosides 4, 5, 7.