title: Daptomycin antibiotic lock therapy in a rat model of staphylococcal central venous catheter biofilm infections.
abstract: Antibiotic lock therapy (ALT) is an adjunctive procedure to prevent or treat central venous catheter infections, ensuing catheter-related bacteremia, and catheter-related metastatic infections. Daptomycin is a cyclic lipopeptide that is rapidly bactericidal against methicillin-susceptible and -resistant Staphylococcus aureus. The efficacies of daptomycin against central venous catheter biofilms, catheter-related bacteremia, and catheter-related metastatic infections were evaluated by adapting a previously reported central venous catheter biofilm model in rats. Combined daptomycin ALT and systemic dosing resulted in the clearance of an established in vivo S. aureus central venous catheter biofilm after just two daily ALT treatments (30 min with daptomycin at 5 mg/ml) with concurrent systemic daptomycin dosing (40 mg/kg of body weight/day subcutaneously [s.c.]; equivalent exposure of 6 mg/kg/day in people). Daptomycin ALT solutions formulated in either saline or lactated Ringer's solution were equally fast in eradicating established in vivo methicillin-resistant Staphylococcus epidermidis (MRSE) central venous catheter biofilms. However, the lactated Ringer's formulation was superior to that of saline in sustaining the bacterial clearance of treated central venous catheters (83% versus 50%). In MRSE-infected central venous catheter studies, 3 days of daptomycin or vancomycin ALT (18 h at 5 mg/ml) with systemic s.c. dosing (40 mg/kg/day daptomycin or 100 mg/kg/day vancomycin) was equally effective 1 week posttherapy in maintaining cleared central venous catheters (90% [n = 10] versus 100% [n = 8]). These results suggest that daptomycin ALT, along with systemic dosing, could be an effective treatment option for the prevention or eradication of staphylococcal central venous catheter biofilm infections, thereby reducing the occurrence of catheter-related bacteremia or catheter-related metastatic infections.
authors.affiliation: Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, MA 02421, USA.
authors.forename: Andrew D G
authors.initials: AD
authors.lastname: Van Praagh
authors.forename: Tongchuan
authors.initials: T
authors.lastname: Li
authors.forename: Shuxin
authors.initials: S
authors.lastname: Zhang
authors.forename: Anu
authors.initials: A
authors.lastname: Arya
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: Xi-Xian
authors.initials: XX
authors.lastname: Zhang
authors.forename: Shellie
authors.initials: S
authors.lastname: Bertolami
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Mortin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D017576:Daptomycin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin