Intravenous flucloxacillin treatment is associated with a high incidence of hypokalaemia

Abstract

Intravenous flucloxacillin is one of the most frequently used high-dose penicillin therapies in hospitalized patients, forming the cornerstone treatment of invasive Staphylococcus aureus infection. Being a nonreabsorbable anion, flucloxacillin has been suggested to cause hypokalaemia, although the frequency and magnitude of this unwanted effect is unknown. In a retrospective cohort, we investigated the incidence and extent of hypokalaemia after initiation of intravenous flucloxacillin or ceftriaxone therapy. In total, 77 patients receiving flucloxacillin (62% male, mean age 70.5 years) and 84 patients receiving ceftriaxone (46% male, mean age 70.8 years) were included.Hypokalaemia occurred significantly more often in patients receiving flucloxacillin than ceftriaxone (42% vs 14%, p < 10 −4 ). Moreover, follow-up potassium levels were significantly lower during flucloxacillin therapy. In general, women were more prone to develop hypokalaemia than men. In conclusion, intravenous flucloxacillin use is associated with a striking incidence of hypokalaemia. Therefore, standardized potassium measurements are necessary.

Hypokalaemia in patients treated with intravenous flucloxacillin: Incidence and risk factors

“…The incidence of hypokalaemia in our study was lower compared to the cohort study from Van der Heijden et al (23.7% vs 42%) 5 . As flucloxacillin‐induced hypokalaemia is considered to develop dose‐dependently, this difference is likely explained by the inclusion of patients with high‐dose flucloxacillin only (≥6 g/24 h) in the study by Van der Heijden et al 5 This assumption is confirmed by the incidence of 50% in the subgroup with high‐dose flucloxacillin (>8 g/24 h) in our study.…”

“…We found that the incidence of hypokalaemia was 23.7%. As this is notably higher than previous reports (approximately 13.5%), our study confirms that intravenous flucloxacillin treatment is associated with an increased risk of developing hypokalaemia 1,5 . The incidence of hypokalaemia in our study was lower compared to the cohort study from Van der Heijden et al (23.7% vs 42%) 5 .…”

“…The European summary of product characteristics (SmPC) describes hypokalaemia as an adverse event with an unknown incidence 10 . In a small cohort study, the cumulative incidence of hypokalaemia was 42% in patients receiving high‐dose (≥ 6 g/24 h) intravenous flucloxacillin 5 . Female sex and the use of diuretics were associated with an increased risk of hypokalaemia in this study.…”

“…A population which might benefit from frequent potassium measurements and subsequent interventions are patients treated with intravenous flucloxacillin. Flucloxacillin is a key drug in the treatment of Staphylococcus aureus infections and has been associated with an increased risk of hypokalemia 5–7 . The exact mechanism of flucloxacillin‐induced hypokalaemia has not been elucidated, but it is assumed to be a class effect of penicillins.…”

Long-term renal outcome in methylmalonic acidemia in adolescents and adults

“…Methylmalonate acts as nonreabsorbable anions, enhancing potassium excretion by increasing transtubular potential difference. Such non-reabsorbable anion effect has long been well described with penicillins, also acting as non-reabsorbable anion [ 34 , 35 ]. Indeed, we found a positive correlation between urinary potassium and urinary methylmalonate as well as a negative correlation between serum potassium and urinary methylmalonate.…”