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Authors: Paul D. Holtom, MD, Charalampos Zalavras, MD, Kenneth C. Lamp, PharmD, Nami Park, PharmD, Lawrence V. Friedrich, PharmD

Title: Clinical Experience with Daptomycin for Foot or Ankle Osteomyelitis

Addresses: Univ. of Southern Calif. Keck School of Medicine, Los Angeles, CA; Cubist Pharmaceuticals, Lexington, MA

Purpose: Daptomycin is a novel antibiotic recently approved in May 2006 for Staphylococcus aureus bloodstream infections including right-sided infective endocarditis and previously for complicated skin and skin structure infections in 2003. The purpose of this analysis is to describe data for osteomyelitis from a registry.

Methods: Cubicin®Outcomes Registry and Experience (CORE 2004) is a multicenter, retrospective, observational chart review of characteristics and clinical outcome of daptomycin treated patients (pts) in 2004. Investigators collected demographic, disease state, clinical and microbiologic data as part of CORE 2004. In a followup study, investigators collected additional data including post-therapy outcomes. This analysis describes the results from pts with foot or ankle osteomyelitis.

Results: 25 patients with foot or ankle osteomyelitis were treated with daptomycin at an average dose of 5.4 mg/kg (range, 4.0-6.2 mg/kg) and average duration of therapy of 34 days (range, 6-59 days). The median follow-up interval was 69 days (range 3-540 days). A majority, 92%, had received daptomycin as secondary or tertiary therapy and 60% had failed prior antibiotic therapy. Diabetes was the most common underlying disease (40%). Concomitant antibiotics were given in 44%; primarily for Gram-negative and/or anaerobic coverage. Gram-positive pathogens, MRSA most common (55%), were identified in 22 (88%) patients; 64% monomicrobial, 24% polymicrobial. Outcomes (cure, improved, failure) at end of therapy were 64%, 32%, 4% and at follow-up were 76%, 12%, 12%. An average of 1.8 followup antibiotics were given to 13 (52%) pts for a median of 30 days (range 8-232 days); most frequently trimethoprim/ sulfamethoxazole, minocycline, rifampin, clindamycin and levofloxacin. The presence of diabetes or use of concomitant or followup antibiotics did not have a significant effect on outcomes. Four patients with an orthopedic devices (all removed) were successfully treated. Surgical bone debridement was performed in 68% and could have influenced success rates (94% with debridement vs 75% without debridement, P = 0.23). Success rates by dose were: =4 mg/kg (80%), >4 to <6 mg/kg (86%) and =6 mg/kg (92%); however, these differences were only observed in the group that did not receive bone debridement.

Discussion: Daptomycin appears successful for foot and ankle osteomyelitis caused by Gram-positive bacteria (including MRSA) particularly when used with higher doses and surgical intervention. Prospective, controlled clinical trials of daptomycin for osteomyelitis are warranted.

Musculoskeletal Infecton Society
Musculoskeletal Infecton Society