Daptomycin-Induced Hyperkalemia in the Absence of Creatinine Kinase Elevation: A Challenging Diagnosis in a Patient with Diabetes and Acute on Chronic CKD

Introduction: Daptomycin is a cyclic lipopeptide antimicrobial, and although known for its potential to cause rhabdomyolysis, isolated hyperkalemia is unusual. Regardless, it is essential to remain mindful of this uncommon association to optimize management. We present a rare case of daptomycin-induced hyperkalemia. Case Description: A 66-year-old female with CKDIII, DMII, HTN, recent MRSA bacteremia in the setting of chronic foot wounds was admitted for worsening AKI. Ten days prior to admission, her Cr increased from 1.5 to 1.83, and vancomycin was changed to daptomycin 600mg every 48 hours. Other pertinent home medications included cefepime 2g/d, torsemide 20mg/d, lisinopril 5mg/d, and metoprolol succinate 25mg/d. There was no evidence of urinary retention, and she had a bland UA. The diuretic and ACEi were held. On day 3 of admission, labs were notable for K 6.2, CO2 14, AG 12, Cr 2.66, glucose 253. CPK was within normal limits throughout a 14-day admission, and there was no evidence of hemolysis. She received temporizing agents, bicarb containing fluids, and sodium zirconium 10mg TID. The recorded urine output was 1-3L/d, but she had persistent hyperkalemia despite IVF administration, treatment of acidosis, glycemic control, and a renal diet. The daptomycin was changed to doxycycline on day 9, and within 48 hours, her K began to downtrend, normalizing at 72 hours while Cr was 3.08. Three months later, her K remained normal, and Cr improved to 1.8. Discussion: According to a prospective study, roughly 1/3 of all inpatient hyperkalemia is attributable to medications. Daptomycin is bactericidal and is known to create cell membrane pores allowing for the movement of cations, including potassium. It has been postulated that daptomycin may allow for potassium shifts without subsequent cell lysis, causing hyperkalemia without an elevated CPK. As for this patient, it is important to consider this as her hyperkalemia was challenging to control with prolonged hospitalization prior to daptomycin discontinuation. Timely recognition of daptomycin-induced hyperkalemia should be considered in the differential to improve outcomes.