Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry

Abstract

Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin® Outcomes Registry and Experience (EU-CORESM) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections.

Staphylococcus aureus-Associated Musculoskeletal Infections

“…In such case, alternative therapies should be considered (e.g., daptomycin). While daptomycin is not approved for the treatment of bone and joint infections, its efficacy in osteomyelitis has been demonstrated (Malizos et al 2016;Roux et al 2016) and recent guidelines suggest this antibiotic as alternative therapy (Berbari et al 2015). The guidelines recommend higher dosages of 6-8 mg/kg/day (Berbari et al 2015), which is supported by data from clinical reports (Roux et al 2016;Seaton et al 2015).…”

Bone penetration of daptomycin in diabetic patients with bacterial foot infections

“…Daptomycin has been registered for the treatment of rightsided endocarditis, S. aureus bacteremia, and complicated skin and soft tissue infections, with recommended once daily intravenous dosing of 6 mg/kg or 4 mg/kg (Liu et al, 2011;Habib et al, 2015). However, due to the evolution of antimicrobial resistance and to its intrinsic microbiological properties, daptomycin has been used in many other settings, in particular for the treatment of bone and joints infections with or without the presence of prosthetic material, and for the treatment of diabetic foot infections (DFI) (Malizos et al, 2016). In a pooled analysis of the two large real-world registries, CORE in the USA and EU-CORE in Europe, daptomycin usage was analysed in 11 557 patients, of whom 8.6% were treated for osteomyelitis, with or without material, with an estimated clinical success rate of 77.7%.…”

“…In a pooled analysis of the two large real-world registries, CORE in the USA and EU-CORE in Europe, daptomycin usage was analysed in 11 557 patients, of whom 8.6% were treated for osteomyelitis, with or without material, with an estimated clinical success rate of 77.7%. The promising role of daptomycin in such infections has been strengthened by the ability to use higher dosages of this molecule, up to 12 mg/kg, but also by in vitro studies showing its ability to penetrate bone tissue (Malizos et al, 2016;Seaton et al, 2016;Senneville et al, 2016). Traunmüller et al provided the first in vitro data regarding daptomycin bone penetration in 2010.…”

Anin vitrobiofilm model ofStaphylococcus aureusinfection of bone

“…), a review of clinical outcomes for treatment of osteomyelitis and orthopaedic device infection (EU‐CORE SM ) reported efficacy in 82·7% of S. aureus infections (Malizos et al . ). Work to further improve and expand its use continues, particularly for high dose delivery via polymethyl methacrylate (PMMA) bone cement (Eick et al .…”