Timing of Antimicrobial Lock Replacement for Gram-Positive Port Infections: Results of a Randomized Trial

<b>Background</b>: Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALSs). We aimed to evaluate whether ALSs could remain effective with extended dwell times of up to 10 days. <b>Methods</b>: In this randomized clinical trial, patients with noninfected, recently implanted ports were assigned to one of five ALS dwell-time groups, ranging from 1 to 10 days. Each ALS contained heparin plus an antimicrobial at standard intraluminal concentrations: vancomycin 2 mg/mL, teicoplanin 10 mg/mL, linezolid 1.8 mg/mL, daptomycin 5 mg/mL, or tigecycline 4.5 mg/mL. The primary endpoint was the time at which intraluminal drug concentrations decreased below 1 mg/mL (ClinicalTrials.gov NCT01592032). <b>Results</b>: Vancomycin and linezolid concentrations fell significantly below 1 mg/mL after 3 days of dwell time. Daptomycin and tigecycline concentrations decreased significantly after 7 days but remained above 1 mg/mL. Teicoplanin concentrations did not decline significantly after 7 days. <b>Conclusions</b>: Optimal ALS dwell time depends on the antimicrobial agent. Vancomycin and linezolid locks require daily replacement, whereas daptomycin, tigecycline, and teicoplanin locks maintain therapeutic concentrations for up to 7 days. These findings support individualized ALS replacement strategies, potentially reducing the need for daily interventions.