Rifampicin-containing combinations are superior to combinations of vancomycin, linezolid and daptomycin againstStaphylococcus aureusbiofilm infectionin vivoandin vitro

Abstract

Susceptibility to antibiotics is dramatically reduced when bacteria form biofilms. In clinical settings this has a profound impact on treatment of implant-associated infections, as these are characterized by biofilm formation. Current routine susceptibility testing of microorganisms from infected implants does not reflect the actual susceptibility, and the optimal antibiotic strategy for treating implant-associated infections is not established. In this study of biofilm formation in implant-associated osteomyelitis, we compared thein vitroandin vivoefficacy of selected antibiotics alone and in combination againstStaphylococcus aureus.We tested vancomycin, linezolid, daptomycin and tigecycline alone and in combination with rifampicin, vancomycin, linezolid and daptomycin againstS. aureusIn vitro, biofilm formation dramatically reduced susceptibility by a factor of 500-2000.In vivo, antibiotic combinations were tested in a murine model of implant-associated osteomyelitis. Mice were infected by inserting implants colonized withS. aureustrough their tibia. After 11 days, the animals were divided into different groups (five animals/group) and given 14 days of antibiotic therapy. All antibiotics resulted in a reduced bacterial load in the infected bone surrounding the implant. Overall, the most effective antibiotic combinations contained rifampicin. Combinations containing two non-rifampicin antibiotics were not more active than single drugs.

Hyperbaric Oxygen Therapy is Ineffective as an Adjuvant to Daptomycin with Rifampicin Treatment in a Murine Model of Staphylococcus aureus in Implant-Associated Osteomyelitis

“…Finally, bacteria were suspended in 3% Tryptic Soy Broth (TSB) at a concentration of 1.5 × 10 6 colony forming units (CFU) per mL. Minimum inhibitory concentration (MIC) for daptomycin were 0.38 mg/L and 0.008 mg/L for rifampicin and the minimum biofilm eradication concentration (MBEC) value for daptomycin was 1024 mg/L as previously reported [33]. …”

Antibiotic treatment of biofilm infections

“…Regarding other biofilm settings, it has been found that combined treatment with clarithromycin plus daptomycin is useful to eradicate staphylococcal biofilms formed on orthopedic devices . Likewise, in another recent work, rifampicin‐containing combinations were superior to combinations of vancomycin, linezolid and daptomycin against S. aureus biofilm infection in vivo and in vitro . Other combinations such as ceftaroline plus daptomycin or vancomycin with fosfomycin were found to display potent activity against biofilm‐producing MRSA, thus providing a potential option for difficult‐to‐treat medical device infections.…”

Preparation, in vitro release and antibacterial activity evaluation of rifampicin and moxifloxacin-loaded poly(D,L-lactide-co-glycolide) microspheres

“…Studies have shown that quinolones can effectively kill gramnegative bacteria in biofilms. Quinolones combined with RIF can significantly improve the success rate of osteomyelitis treatment and reduce the risk of bacterial resistance [18][19][20]. Clinically, Staphylococcus species comprises the major pathogenic bacteria that cause implant-or post-trauma-related bone infections.…”