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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.