Nafcillin use was associated with a greater rate of hypokalemia development in hospital than oxacillin, a new comparative study has found. Acute kidney injury (AKI) incidences were also higher in those administered nafcillin than those who received oxacillin. The study is the first to directly compare tolerability of both drugs.

The study included a total of 224 patients who received 12g/day of naficillin or oxacillin (160 naficillin and 64 oxacillin), based on physician preference. The most common indications for treatment were bacteremia (44%, 98/224), bone and joint infections (22%, 50/224), and endocarditis (21%, 46/224).

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Fifty-one percent of patients who developed hypokalemia were treated with nafcillin compared to 17% who received oxacillin. Higher rates of severe hypokalemia (potassium level ≤ 2.9 mmol/L) and an acute drop in potassium (≥ 0.5 mmol/L decrease from baseline) were also seen in the nafcillin group (20%, 32/160 and 56%, 90/160) compared to the oxacillin group (3%, 2/64 [P=0.0008] and 34%, 22/64 [P=0.005]).

AKI occurred in 18% (29/160) of patients in the nafcillin group compared to 6% (4/64) of patients in the oxacillin group (p=0.03), while rates of abnormal liver function tests were comparable between both groups. Patients who received nafcillin also had a longer duration of hospital stays.

Adverse events associated wit these antibiotics led to early treatment termination in 18% of nafcillin patients and 2% of oxacillin patients; discontinuation due to hypokalemia or AKI was only identified in patients treated with nafcillin. Compared to patients receiving oxacillin, patients treated with nafcillin stayed in the hospital for a median 3.5 days longer.

The authors call for more randomized controlled studies to test their findings; they suggest that the implications if corroborated, could be significant. Given how both treatments have similar pharmacokinetics, costs, and efficacy, proving the superiority of one treatment could influence future treatment decisions.

The authors conclude by asserting, “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.”

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