Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis.
BACKGROUND
Infection due to methicillin-resistant Staphylococcus aureus (MRSA) is increasingly common in nosocomial and community settings. Daptomycin is a cyclic lipopeptide anti-infective with activity against MRSA, approved for treatment of complicated skin and skin structure infections. Daptomycin may be useful in systemic or local treatment of chronic osteomyelitis.


METHODS
We measured mechanical strength of daptomycin- and vancomycin-loaded polymethylmethacrylate (PMMA), assayed in vivo release of daptomycin and vancomycin from daptomycin- and vancomycin-loaded PMMA, respectively, and compared the efficacy of two systemic doses of daptomycin with that of vancomycin, each with or without the respective anti-infective loaded into PMMA, using a rat model of MRSA chronic osteomyelitis.


RESULTS
Neither tensile nor compressive strength of PMMA was impacted by impregnation with these antimicrobials at a concentration of 7.5% by weight. The peak concentrations of daptomycin and vancomycin in rat tibial bone surrounding a 7.5% daptomycin- and vancomycin-loaded 3 mm PMMA bead were 178 and 49 mg/L, respectively. In the treatment of experimental osteomyelitis, rats assigned to no treatment, daptomycin 50 mg/kg subcutaneously twice daily, daptomycin 60 mg/kg subcutaneously twice daily, and vancomycin 50 mg/kg intraperitoneally twice daily had 6.4, 4.1, 4.0 and 4.5 median log10 cfu/g of bone at the end of 21 days of therapy. All systemic anti-infectives studied were more active than was no treatment. Daptomycin- or vancomycin-loaded PMMA did not, however, exhibit microbiological efficacy alone or adjunctively, as assessed 21 days after implantation.


CONCLUSIONS
Daptomycin is released from PMMA in vivo at a rate similar to that of vancomycin. Systemic daptomycin is as active as vancomycin in a rat model of chronic MRSA experimental osteomyelitis.
Rouse
Mark S
MS
Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Piper
Kerryl E
KE
Jacobson
Melissa
M
Jacofsky
David J
DJ
Steckelberg
James M
JM
Patel
Robin
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002908:Chronic Disease; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005079:Excipients; D006245:Hardness Tests; D008297:Male; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000188:drug therapy* / Q000473:pathology; D019904:Polymethyl Methacrylate; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D005079:Excipients; D014640:Vancomycin; D019904:Polymethyl Methacrylate; D017576:Daptomycin