Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant

Abstract

We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log10 CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log10 CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.

Clinical, Bacteriological, and Genetic Characterization of Bone and Joint Infections Involving Linezolid-Resistant Staphylococcus epidermidis: a Retrospective Multicenter Study in French Reference Centers

“…The CRIOGO centers have solid experience of linezolid use in the treatment of device infections. Animal studies demonstrated its efficacy in the treatment of BJIs due to Gram-positive cocci ( 26 , 27 ), and clinical data showed satisfactory efficacy in the treatment of device infections ( 28 ). The incidence of LR-MDRSE carriage appears to be directly related to linezolid consumption in health care facilities ( 14 – 19 ), and reducing consumption of oxazolidinones could help limit this incidence ( 17 ).…”

Efficacy of rifampicin combination therapy against MRSA prosthetic vascular graft infections in a rat model

“…All administrations were given intraperitoneally, treatment duration was seven days. Dosing frequency and actual dosage was based on previous studies on all drugs and reflect common practice when using the selected antibiotics in rat models of S. aureus infection [ [22] , [23] , [24] , [25] ]. Rats were sedated followed by removal of the graft and euthanized by cervical dislocation 36 h after the final administration of treatment to ensure antibiotics washout before CFU enumeration.…”

Efficacy of ceftaroline and rifampin, alone or combined, in a rat model of methicillin-resistant Staphylococcus epidermidis osteomyelitis without implant

“…3 . The tibia osteomyelitis rat model was established as previously described by Albac et al ( 22 ). Animals were anaesthetized by intraperitoneal administration of ketamine (90 mg/kg of body weight, Virbac) and xylazine (10 mg/kg of body weight, Bayer).…”

“…Animals were randomly assigned to one of the four study arms: no treatment (0.9% saline serum), ceftaroline alone (20 mg/kg/12 h), rifampin alone (25 mg/kg/12 h), ceftaroline (20 mg/kg/12 h), and rifampin (25 mg/kg/12 h). Ceftaroline dose used in our published rat osteomyelitis model was administered, and rifampin dose was selected on the basis of data published in a rat model of MRSA osteomyelitis ( 22 , 41 )).…”

“…Ceftaroline, a cephalosporin with potent activity against methicillin-resistant staphylococci approved by the US Food and Drug Administration (FDA) in 2010 and by the European Medicines Agency (EMA) in 2012, demonstrated high clinical success rates in treating MRSA osteomyelitis in some case reports and in the CAPTURE study experience ( 19 – 21 ). In addition to its in vitro activity against Staphylococcus epidermidis including MRSE strains, ceftaroline also recently demonstrated its safe and significant efficacy when used in monotherapy in a preclinical model of MRSE osteomyelitis and in an experimental model of foreign-body MRSE infection ( 22 , 23 ). However, little is known about the penetration of ceftaroline into the bone in the context of MRSE osteomyelitis and on its efficacy when used in combination with rifampin.…”