Case Presentation:

A 65–year–old–man with coronary artery disease, hypertension and hyperlipidemia presented with neck pain and limb weakness. Outpatient medications included furosemide 40 mg daily and potassium chloride 10 mEq daily. Blood pressure was 126/75 mm Hg, pulse 74, and BMI 28. Serum sodium was 138 mEq/L, potassium 3.5 mEq/L, chloride 103 mEq/L, bicarbonate 25 mEq/L, urea nitrogen 31 mg/dL, and creatinine 1.2 mg/dL. An MRI suggested C5–C6 osteomyelitis prompting drainage and fusion. On day # 3,wound cultures grew nafcillin–sensitive Staphylococcus aureus, and he was treated with 2 g of this agent every four hours. On day #10, the serum potassium was 2.9 mEq/L, magnesium 2.0 mg/dL, BUN 5 mg/dl, and creatinine 0.92 mg/dL. He received 350 mEq of Potassium supplementation orally and intravenously over next 48 hrs, but he remained hypokalemic. Urine studies on day #12 showed K 61.5 mEq/L, Na 73 mEq/L, Cl 127 mEq/L, 496 mOsm/L. The calculated urine anion gap was 8. The BUN became immeasurably low by day #12. The transtubular potassium gradient was 12, suggesting urinary K wasting. Nafcillin was discontinued one day later and the serum potassium promptly normalized from 2.9 to 4.0 mEq/L within 10 hours.


Hypokalemia is a common, clinically important electrolyte imbalance, with potential complications such as muscle weakness, ileus and cardiac dysrhythmias. Penicillins such as nafcillin and oxacillin are established causes of hypokalemia; however, the mechanism whereby hypokalemia is induced by these agents remains poorly elucidated. We present a patient with staphylococcal cervical osteomyelitis in whom treatment with nafcillin sodium resulted in refractory hypokalemia. There are three proposed mechanisms of Nafcillin–induced hypokalemia: (1) nafcillin’s impermeant anion effect on the distal tubule, (2) the increased sodium load of the antibiotic preparation on the distal tubule leading to potassium wasting, and (3) an antibiotic–associated cellular redistribution effect. Our patient had urinary potassium losses, supporting the sodium load and impermeant ion effect mechanisms. The immeasurably low BUN, which corrected after antibiotic discontinuation, also supports the increased tubular flow theory. However, the absent urine anion gap and the normal urine Cl do not support the presence of urinary nafcillin; and the immediate correction of serum potassium after nafcillin discontinuation supports the cellular redistribution theory.


Nafcillin induced hypokalemia is rare, with only three documented cases in the literature. We suggest that hypokalemia remains an important, poorly understood and overlooked complication associated with nafcillin therapy, and the etiology may be multifactorial, with a combination of potassium. Redistribution and urinary potassium losses. The most effective treatment, as in this case, is antibiotic discontinuation.