SLR - January 2012 - Kim Dao
Reference: Traunmuller, F., Schintler, M., Metzler, J., Spendel, S., Mauric, O. (2010) Soft Tissue and Bone Penetration Abilities of Daptomycin in Diabetic Patients with Bacterial Foot Infections. Journal of Microbial Chemotherapy. 65 (6): 1252-1257.
Scientific Literature Review
Reviewed by: Kim Dao, DPM
Residency Program: Botsford General Hospital
Podiatric Relevance:
As an increase is seen in methicillin-resistant soft tissue infection in the current patient population, an alternative antibiotic is needed to treat these patients with bacterial foot infections. Current strategies in the therapy of diabetic patients suffering from complicated diabetic foot infections need to be developed to eradicate the causative pathogen. Daptomycin has been under recent skepticism as to whether its efficacy proves to have potent soft tissue and bone penetration for treatment of bacterial foot infections.
Methods:
A clinical microdialysis study was conducted using nine patients with type II diabetes presenting with deep-seated bacterial foot infections. All patients required surgical debridement with partial metatarsal bone resection and adjuvant systemic antimicrobial therapy. Exclusion criteria included allergy to daptomycin, pre-treatment with daptomycin within 1 week before the screening visit, pregnancy, renal dysfunction, and knowledge of pre-existing myopathy. Patients received four to five intravenous infusions of daptomycin at a dose of 6 mg/kg over 30 minutes once daily prior to the start of the microdialysis procedure. Using microdialysis technique, interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone was collected. Serial sampling of specimen was performed from 0 to 8 hour spost-dose in five patients (Group A) and from 8 to 16 hours after study drug administration in four patients (Group B).
Results:
The pharmacokinetics of daptomycin was assessed on nine patients. The key finding was that free daptomycin in plasma equilibrates completely with soft tissues and bone within 3 hours after the start of a 30 minute infusion. Inflammation did not affect daptomycin's concentrations at the target site. The mean ratios of the tissue to plasma were 1.44, 0.98 and 1.08 for unaffected soft tissue, inflamed subcutaneous tissue and bone, respectively. At steady-state, the free concentrations of daptomycin in all compartments studied were found to exceed the MIC for relevant gram-positive bacteria, such as methicillin-susceptible S. aureus and MRSA.
Conclusions:
Based on these study results, free concentrations of daptomycin achieved in subcutaneous adipose tissue and bone after administration of multiple doses of 6 mg/kg were sufficient to cover MRSA and other gram-positive bacteria commonly found in diabetic patients with foot infections, including osteomyelitis.