Randomized controlled trial of the safety and efficacy of Daptomycin versus standard-of-care therapy for management of patients with osteomyelitis associated with prosthetic devices undergoing two-stage revision arthroplasty.
The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.
Nuffield Orthopaedic Centre, Oxford, United Kingdom.
Ivor
I
Byren
Shruta
S
Rege
Ed
E
Campanaro
Sara
S
Yankelev
Diane
D
Anastasiou
Gennady
G
Kuropatkin
Richard
R
Evans
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D015415:Biomarkers / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006622:Hip Prosthesis / Q000382:microbiology; D006801:Humans; D007720:Knee Prosthesis / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000601:surgery; D010406:Penicillins / Q000494:pharmacology / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013582:Synovial Fluid / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D010406:Penicillins; D014640:Vancomycin; D003402:Creatine Kinase; D017576:Daptomycin