Piperacillin-tazobactam induced hypokalemia: Mechanism

Piperacillin/tazobactam is a commonly used antibiotic with tolerable side effects and broad antimicrobial activity in general practice.

Rare side-effects can include hypokalemia.
WHY? Two theories exist:

1. Piperacillin-sodium is a negatively charged molecule (anion) and nonabsorbable. This increases transepithelial electronegativity in the distal nephron, increasing  potassium (cation) excretion. (-) draws out the (+)
2. The large volume of sodium administered with Piperacillin-tazobactam can result in solute diuresis.

REFERENCES

1. Hussain S, Syed S, Baloch K. Electrolytes imbalance: a rare side effect of piperacillin/ tazobactam therapy. J Coll Physicians Surg Pak. 2010;20(6):419-420.
2. Zaki SA, Lad V. Piperacillin-tazobactam-induced hypokalemia and metabolic alkalosis. Indian Journal of Pharmacology. 2011;43(5):609-610. doi:10.4103/0253-7613.84986.
3. Polderman KH, Girbes AR. Piperacillin-induced magnesium and potassium loss in intensive care unit patients. Intensive Care Med. 2002;28(4):520-522.c