Trimethoprim-associated electrolyte and acid-base abnormalities

Area of Science:

• Pharmacology
• Nephrology
• Internal Medicine

Background:

• Trimethoprim, an antimicrobial, shares structural similarities with potassium-sparing diuretics.
• This structural relationship suggests a potential for trimethoprim to disrupt electrolyte and acid-base homeostasis.
• Previous literature lacked a systematic analysis of individual case reports detailing trimethoprim-induced electrolyte and acid-base derangements.

Purpose of the Study:

• To systematically review and analyze documented cases of electrolyte and acid-base derangements associated with trimethoprim use.
• To identify common electrolyte imbalances and acid-base abnormalities linked to trimethoprim.
• To determine predisposing factors contributing to these adverse events.

Main Methods:

• A systematic review of 53 reports documenting 68 patients (42 males, 26 females; age 23-96 years) experiencing electrolyte or acid-base derangements while on trimethoprim.
• Analysis focused on cases where trimethoprim use averaged approximately 5 days.

Main Results:

• A total of 105 electrolyte imbalances were observed across 68 patients.
• Hyperkalemia (>5.0 mmol/L) occurred in 91% (62 patients), hyponatremia (<135 mmol/L) in 43% (29 patients), and metabolic acidosis (pH<7.38, bicarbonate <19 mmol/L) in 21% (14 patients).
• Predisposing factors identified in 79% (54 patients) included high-dose trimethoprim, concurrent medications, pre-existing kidney disease, age ≥80 years, and diabetes mellitus.

Conclusions:

• High-dose trimethoprim, co-administration with interacting drugs, impaired kidney function, advanced age (≥80 years), and diabetes mellitus are significant risk factors for trimethoprim-associated electrolyte and acid-base abnormalities.
• Clinicians should identify at-risk patients, consider avoiding potentially harmful drug combinations, and implement regular laboratory monitoring.