Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections

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Abstract
Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by Staphylococcus epidermidis ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 10 8 CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 10 7 CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 10 7 CFU/coupon at 24 h, 4.3 × 10 6 CFU/coupon at 72 h, 1.4 × 10 5 CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 10 7 CFU/coupon at 24 h, 3.7 × 10 6 CFU/coupon at 72 h, 8.4 × 10 6 CFU/coupon at 168 h, and 6.5 × 10 6 CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 10 5 CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of S. epidermidis biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml).

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