The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection. Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter "locked" with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed. Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.