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

Abstract

b 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 twentyfour 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.

Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin

“…Although our results demonstrate that both nafcillin and oxacillin have an inferior safety profile compared to cefazolin, subgroup analyses according to the type of antistaphylococcal penicillin did not identify significant differences, with the exception of higher nafcillin discontinuation rates due to ADRs in outpatients. A previous study found that nafcillin was associated with a high discontinuation rate due to ADRs compared to oxacillin (30). The results of our analysis are unable to confirm or refute this finding since we did not perform a head-to-head analysis, and the oxacillin subgroup could be simply underpowered.…”

A Patient with Nafcillin-Associated Drug-Induced Liver Failure

“…Since then, there have been only a few case reports and 2 cohort studies on the subject. The first cohort study by Viehman et al [ 2 ] followed 224 patients at a single institution who were receiving antibiotics for more than 1 month. Within this population, 3% of oxacillin users and 4% of nafcillin users developed acute hepatic toxicity, without a significant difference in rates between the 2 groups [ 2 ].…”

“…The first cohort study by Viehman et al [ 2 ] followed 224 patients at a single institution who were receiving antibiotics for more than 1 month. Within this population, 3% of oxacillin users and 4% of nafcillin users developed acute hepatic toxicity, without a significant difference in rates between the 2 groups [ 2 ]. The second cohort study followed 222 children on antibiotics for 4 years and revealed an acute hepatitis rate of 22% for oxacillin and 0% for nafcillin [ 1 ].…”

A Case of Hypokalemia Possibly Induced by Nafcillin

“…The reviewed literature suggested that drug-induced hypokalemia rarely occurs after starting therapy with penicillin-type antimicrobials, such as nafcillin [1,3,6,7,8], with the baseline potassium level being a key determinant in the development of hypokalemia [7]. Patients with a higher baseline potassium level had a lesser likelihood of developing severe hypokalemia but had a higher likelihood of having an acute drop in the potassium level [7]. Although this patient’s baseline potassium was around 4.3 meq/L, there was an acute drop in his potassium levels to less than 3.5 meq/L once nafcillin was started.…”

“…Less common causes are renal tubular acidosis, diabetic ketoacidosis, excess insulin, primary hyperaldosteronism, ectopic adrenocorticotropic hormone production, and medications [2,3,4,5,6]. Drug-induced hypokalemia rarely occurs after starting therapy with penicillin-type antimicrobials, such as nafcillin [1,3,6,7,8].…”