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BACKGROUND: Catheter-related bloodstream infections (CRBSI) are a leading cause of nosocomial infections associated with significant mortality and costs. The objective of this study was to determine the rate of CRBSI in two large Swiss hospitals and to identify risk factors for this condition. PATIENTS AND METHODS: During 1 year all central venous catheter (CVC)-inserted in patients admitted for visceral, orthopedic or urologic surgery at the cantonal hospital in St Gallen and cantonal hospital in Chur were included in the study. Catheters were followed for the duration of their insertion. Blood cultures and semiquantitative cultures from catheters were drawn in the presence of local or systemic signs of infection. Primary endpoint was CRBSI defined as definite if (a) the same pathogen grew in at least one blood culture and from the distal segment of the catheter or (b) the same pathogen grew in at least one peripherally and centrally drawn blood culture and the differential time to positivity of central blood culture vs peripheral blood culture was > 120 min. CRBSI was defined as probable if at least one blood culture was positive with a recognized pathogen in the absence of another site of infection. Data were analyzed using univariate and multivariate time-to-event methods. RESULTS: During the study period, 1,396 CVCs were prospectively studied in 1,162 patients. Incidence density of all CRBSIs (definite n = 29, probable n = 7) was 2.5 (95% CI: 1.8-3.5) per 1,000 catheter-days. The lowest rate of CRBSI was found in subclavian catheters, the adjusted hazard ratio (HR) for jugular catheters was 2.2 (95% CI: 1.1- 4.3; p = 0.03) and for femoral catheters 2.9 (95% CI: 0.6-14.4; p = 0.19). Each additional lumen increased the risk (HR = 4.4; 95% CI: 2.5-7.7; p < 0.001), whereas the permanent blocking of additional lumens was protective (HR = 0.3; 95% CI: 0.1-0.7; p = 0.006). The most commonly isolated organism were coagulase-negative staphylococci with a rate of 28%. CONCLUSION: Number of lumens and site of access were independent risk factors for CRBSI. The use of catheters with multiple lumens should therefore be restricted as far as possible. If a catheter cannot be removed, the permanent closure of unneeded lumens may reduce the risk of CRBSI.