Efficacy of Daptomycin versus Vancomycin in an Experimental Model of Foreign-Body and Systemic Infection Caused by Biofilm Producers and Methicillin-Resistant Staphylococcus epidermidis

Abstract

Staphylococcus epidermidis is a frequent cause of device-associated infections. In this study, we compared the efficacy of daptomycin versus vancomycin against biofilm-producing methicillin-resistant S. epidermidis (MRSE) strains in a murine model of foreign-body and systemic infection. Two bacteremic biofilm-producing MRSE strains were used (SE284 and SE385). The MIC of daptomycin was 1 mg/liter for both strains, and the MICs of vancomycin were 4 and 2 mg/liter for SE284 and for SE385, respectively. The in vitro bactericidal activities of daptomycin and vancomycin were evaluated by using time-kill curves. The model of foreign-body and systemic infection of neutropenic female C57BL/6 mice was used to ascertain in vivo efficacy. Animals were randomly allocated into three groups (n ‫؍‬ 15): without treatment (controls) or treated with daptomycin at 50 mg/kg/day or vancomycin at 440 mg/kg/day. In vitro, daptomycin showed concentration-dependent bactericidal activity, while vancomycin presented time-dependent activity. In the experimental in vivo model, daptomycin and vancomycin decreased liver and catheter bacterial concentrations (P < 0.05) and increased the survival and the number of sterile blood cultures (P < 0.05) using both strains. Daptomycin produced a reduction in the bacterial liver concentration higher than 2.5 log 10 CFU/g compared to vancomycin using both strains, with this difference being significant (P < 0.05) for infection with SE385. For the catheter bacterial concentrations, daptomycin reduced the concentration of SE284 3.0 log 10 CFU/ml more than did vancomycin (P < 0.05). Daptomycin is more effective than vancomycin for the treatment of experimental foreign-body and systemic infections by biofilmproducing methicillin-resistant S. epidermidis. Staphylococcus epidermidis is a common nosocomial and health care-associated pathogen in several infections, causing important morbidity, mortality, and/or health care costs. Thus, it is the most important cause of infections of orthopedic prostheses, accounting for approximately 40% of all cases, and between 30% and 50% of catheter-related bacteremias are caused by coagulasenegative Staphylococcus (CNS) strains (19,26). Other severe and/or frequent nosocomial and health care-associated infections are also caused by CNS, being the etiology in the 22.7% of endocarditis infections (9, 13) and in 37 to 78% of cerebrospinal fluid shunt-associated infections (4, 11).Moreover, the high frequency of methicillin-resistant S. epidermidis (MRSE) is an important therapeutic problem.

Preventing Implant-Associated Infections by Silver Coating

“…In case of DAP, a dose of 50 mg/kg body weight was chosen to obtain an AUC 0 -24 similar to that in humans after a dose of 6 mg/kg body weight (22,30).…”

“…Despite this broad clinical use, little is known about the stability of silvercoated alloys, their efficacy on biofilm-forming bacteria-especially in combination with antibiotics-and the kinetics of release. Moreover, silver has a broad range of bacterial targets, including the respiratory chain (21)(22)(23)(24), and has been shown to induce resistance in Gram-negative bacteria and toxicity in eukaryotic cells (25,26).…”

Inhibition of Staphylococcus epidermidis Biofilm by Trimethylsilane Plasma Coating

“…Washing intensity in the methods of assessing biofilm formation varied among different investigators (3,21,25,56). In order to assess the impact of washing intensity on estimation of bacterial load in biofilms, additional experiments were performed in which the biofilms on the wafers were washed with PBS for eight times.…”

Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement

“…Second, daptomycin has a high and very rapid concentration-dependent bactericidal activity (8)(9)(10)(11), not affected by decreased susceptibility to vancomycin (12). Third, daptomycin shows an antimicrobial activity in an in vivo model of acute osteomyelitis (13) and penetrates rapidly into biofilms (14,15); also, due to its unique mechanism of action on cell membrane, daptomycin retains antimicrobial activity against both stationary-phase cultures of staphylococci within the biofilm and bacteria in the multiplication phase (16)(17)(18)(19)(20). Finally, the safety and tolerability of daptomycin have been established (21)(22)(23).…”