Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin

Nafcillin and oxacillin are used interchangeably in clinical practice, yet few studies have evaluated the safety of these two agents. Our objective was to compare the differential tolerabilities of nafcillin and oxacillin among hospitalized patients. We conducted a retrospective cohort study of all patients who received 12 g/day of nafcillin or oxacillin for at least 24 h. Two hundred twenty-four patients were included. Baseline characteristics and comorbidities were similar among patients receiving nafcillin (n = 160) and those receiving oxacillin (n = 64). Hypokalemia, defined as a potassium level of ≤3.3 mmol/liter or ≤2.9 mmol/liter or as a ≥0.5-mmol/liter decrease from the baseline level, occurred more frequently among patients who received nafcillin (51%, 20%, and 56%, respectively) than among those who received oxacillin (17%, 3%, and 34%, respectively; P < 0.0001, P = 0.0008, and P = 0.005, respectively). By multivariate logistic regression analysis, receipt of nafcillin was an independent predictor of severe hypokalemia (odds ratio [OR] = 6.74; 95% confidence interval [CI], 1.46 to 31.2; P = 0.02). Rates of hepatotoxicity did not differ between groups; however, acute kidney injury occurred more commonly with nafcillin than with oxacillin (18% versus 6%; P = 0.03). Overall, 18% of patients who received nafcillin discontinued therapy prematurely due to adverse events, compared to 2% of patients who received oxacillin (P = 0.0004). Nafcillin treatment is associated with higher rates of adverse events and treatment discontinuation than oxacillin among hospitalized adult patients. These findings have important implications for patients in both inpatient and outpatient settings, particularly patients who require long-term therapy and cannot be monitored routinely. Future randomized controlled studies evaluating the efficacy, costs, and tolerability of nafcillin versus oxacillin are warranted.