Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections among hospitalized patients, contributing significantly to healthcare costs and mortality [1]. In recent years, the incidence of complicated and nosocomial UTIs caused by Gram-positive pathogens, particularly Enterococcus faecalis and Enterococcus faecium, has risen markedly, accounting for nearly 30% of catheter-associated UTIs [2,3,4,5]. These infections pose clinical challenges, especially in vulnerable populations such as the elderly and those with renal impairment. The rising prevalence of multidrug-resistant organisms further complicates UTIs treatment [6], as conventional agents such as trimethoprim-sulfamethoxazole [7], ciprofloxacin [8], and ampicillin [6] increasingly suffer from resistance, narrow therapeutic windows, and tolerability issues. This underscores the urgent need for alternative antimicrobials that are both effective and safe in high-risk patient groups.

Linezolid (LNZ), the first synthetic oxazolidinone antibiotic, offers a promising alternative for treating Gram-positive UTIs. It inhibits bacterial protein synthesis and is active against a broad range of Gram-positive pathogens, including Enterococcus and Staphylococcus species [9]. Pharmacologically, LNZ exhibits area under the curve (AUC)-dependent antibacterial activity, with approximately 30% of the dose excreted unchanged in urine via the kidneys in healthy individuals [[10], [11], [12]]. LNZ’s pharmacokinetic (PK) properties make it a potential candidate for UTIs treatment. Off-label use of LNZ has shown clinical success in treating UTIs caused by Gram-positive pathogens [6], including patients with renal insufficiency [13]. However, it remains unclear whether standard dosing regimens provide sufficient urinary exposure in patients with impaired renal function, as urinary PK data in this population are scarce. A recent study advocating dose adjustments for such patients further emphasize this knowledge gap [14]. Therefore, a better understanding of urinary drug recovery and pharmacokinetic/pharmacodynamic (PK/PD) target attainment is essential to optimize therapy, ensure efficacy, and minimize the risk of toxicity.

Therefore, the main aim of this study was to optimize LNZ dosing for the effective treatment of UTIs in critically ill patients with renal impairment. Specifically, we sought to (1) characterize urinary exposure of LNZ in this population; (2) describe its population pharmacokinetics with respect to renal function; and (3) evaluate PK/PD target attainment under different dosing regimens and propose optimized strategies that balance efficacy and safety.