Which antibiotic, among oxacillin, nafcillin, and cefazolin, is least likely to cause nephritis?

Cefazolin is Least Likely to Cause Nephritis Among Oxacillin, Nafcillin, and Cefazolin

Among oxacillin, nafcillin, and cefazolin, cefazolin is least likely to cause nephritis and is associated with significantly lower rates of acute kidney injury.

Comparative Nephrotoxicity Risk

Evidence for Cefazolin's Lower Nephrotoxicity

• A 2017 study comparing cefazolin to nafcillin found that acute kidney injury occurred in only 13% of patients receiving cefazolin compared to 33% of patients receiving nafcillin (p=0.007) 1
• After adjusting for confounding factors, nafcillin was independently associated with 2.74 times higher odds of developing acute kidney injury compared to cefazolin 1
• A 2019 meta-analysis confirmed that cefazolin treatment is associated with significantly less nephrotoxicity compared to anti-staphylococcal penicillins (relative risk 0.36; 95% CI 0.21-0.59) 2

Oxacillin Nephrotoxicity

• According to the FDA drug label, oxacillin is associated with "renal tubular damage and interstitial nephritis" which can manifest as "rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency" 3
• The FDA label specifically notes that nephropathy induced by penicillins (including oxacillin) is generally reversible upon prompt discontinuation of therapy 3

Nafcillin Nephrotoxicity

• While historically there have been mixed reports about nafcillin nephrotoxicity 4, more recent evidence indicates that nafcillin carries a higher risk of nephrotoxicity compared to cefazolin 1
• Case reports of nafcillin-induced acute interstitial nephritis exist in the literature 5

Mechanism of Nephrotoxicity

Beta-lactam Nephrotoxicity Patterns

• Cephalosporins like cefazolin and penicillins like oxacillin and nafcillin can both cause nephrotoxicity, but through different mechanisms and at different rates 6
• Penicillin-related nephrotoxicity (including oxacillin and nafcillin) often presents as acute interstitial nephritis, which is primarily an immune-mediated hypersensitivity reaction 6
• First-generation cephalosporins like cefazolin have shown lower nephrotoxicity profiles compared to certain other cephalosporins (like cephaloridine) and anti-staphylococcal penicillins 6

Clinical Implications

When Choosing Between These Antibiotics

• For patients with risk factors for kidney injury or existing renal impairment, cefazolin should be preferred over oxacillin or nafcillin when clinically appropriate 1, 2
• When treating methicillin-susceptible Staphylococcus aureus infections, cefazolin appears to be equally effective as anti-staphylococcal penicillins while having a better safety profile regarding nephrotoxicity 2

Monitoring Recommendations

• For patients receiving oxacillin or nafcillin, closer monitoring of renal function is warranted due to the higher risk of nephrotoxicity
• Signs of nephritis to monitor include changes in urinary sediment, proteinuria, hematuria, decreased urine output, and rising creatinine 3

Caveats and Considerations

• While cefazolin has lower nephrotoxicity, it may be subject to the "inoculum effect" with certain S. aureus strains, potentially reducing efficacy in high-burden infections 2
• For endocarditis or deep-seated abscesses, efficacy appears similar between cefazolin and anti-staphylococcal penicillins despite the nephrotoxicity differences 2
• Individual patient factors including allergies, infection site, pathogen, and local resistance patterns should always be considered when selecting between these antibiotics

In conclusion, based on the most recent and highest quality evidence, cefazolin demonstrates the lowest risk of nephritis among oxacillin, nafcillin, and cefazolin, while maintaining comparable clinical efficacy for appropriate indications.