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Updated: Apr 19, 2026

Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis
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Incidence of Acute Kidney Injury With the Use of Nafcillin Versus Oxacillin

Alejandro D Perez1, Autumn L Brenner1, Emilia Pieta2

  • 1Department of Pharmacy, University of North Carolina, Medical Center, Chapel Hill, North Carolina, USA.

Pharmacotherapy
|April 18, 2026
PubMed
Abstract

Insights

Nafcillin is linked to a higher risk of acute kidney injury (AKI) compared to oxacillin in patients treated for Staphylococcus aureus infections. This study highlights important safety differences between these antistaphylococcal penicillins.

Area of Science:

  • Pharmacology and Nephrology
  • Infectious Diseases and Antibiotic Therapy

Background:

  • Antistaphylococcal penicillins (ASPs) like nafcillin and oxacillin are crucial for treating methicillin-susceptible Staphylococcus aureus (MSSA) infections.
  • Despite similar efficacy and pharmacokinetic profiles, emerging evidence suggests differing safety profiles, particularly concerning acute kidney injury (AKI).

Purpose of the Study:

  • To compare the incidence of AKI between nafcillin and oxacillin in adult inpatients.
  • To evaluate secondary outcomes including serum creatinine changes, AKI severity, and mortality.

Main Methods:

  • Retrospective cohort study of 638 adult inpatients receiving at least six doses of nafcillin or oxacillin.
  • Primary outcome: incidence of AKI during treatment.
  • Secondary outcomes: serum creatinine, AKI stage, duration of therapy/hospitalization, mortality, hypokalemia, and hepatotoxicity.

Main Results:

  • AKI occurred in 33.3% of nafcillin patients versus 19.5% of oxacillin patients (adjusted risk ratio 1.55, p < 0.01).
  • Nafcillin was associated with higher AKI incidence across all stages, longer hospitalizations, increased mortality, and greater rates of hypokalemia.
  • Exploratory outcomes also indicated higher rates of moderate and severe hypokalemia with nafcillin.

Conclusions:

  • Nafcillin treatment is associated with a significantly higher incidence of AKI compared to oxacillin.
  • These findings underscore critical safety distinctions between nafcillin and oxacillin, informing clinical decision-making for MSSA infections.
Keywords:
acute kidney injuryantistaphylococcal penicillinnafcillinoxacillin

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