Antimicrobial-induced hyponatremia: pathophysiological mechanisms, implicated agents, and clinical management...

Hyponatremia is a prevalent and serious electrolyte disorder affecting approximately 20% of hospitalized patients, significantly increasing morbidity and mortality. While common causes are well-documented, antimicrobial-induced hyponatremia is frequently underrecognized due to confounding infection-related factors. This review aims to systematically delineate the implicated antimicrobial agents, their underlying pathophysiological mechanisms, and clinical management strategies.

A comprehensive literature search was conducted via PubMed for studies published between January 1, 2000, and August 22, 2025. Data were synthesized to categorize drugs based on risk levels, mechanisms of action, and clinical outcomes. Backward citation tracking was employed to identify additional pertinent cases and mechanistic studies.

The primary pathophysiological drivers identified are the syndrome of inappropriate antidiuresis (SIAD) and direct renal tubular dysfunction. High-risk agents include linezolid, trimethoprim-sulfamethoxazole and voriconazole. Other implicated agents include fluoroquinolones, vidarabine, rifabutin, azithromycin, aminoglycosides, colistin, nitrofurantoin and β-lactam antibiotics. Onset typically occurs within 2 to 14 days of therapy initiation. Key risk factors identified include advanced age (≥ 65 years), renal impairment, supratherapeutic dosing, large-volume hypotonic diluents, and concomitant use of diuretics or SSRIs.

Antimicrobial-induced hyponatremia is an important clinical entity that necessitates a high index of suspicion, particularly in older adults and polymedicated patients. Management focuses on the prompt identification and withdrawal of the offending agent, followed by symptom-stratified sodium correction. This review provides a practical guide to mitigate risks. Future prospective studies are needed to elucidate the mechanisms and clinical characteristics of antimicrobial-induced hyponatremia.

Not applicable.