Purpose Infections of skin and soft tissues are considered to be complicated (cSSSIs) when they involve abnormal skin or wounds, occur in compromised hosts or require surgical intervention. They are typically caused by gram-positive pathogens which are commonly now resistant to beta-lactam antimicrobials and even glycopeptitides. Daptomycin, a new cyclic lipopeptide exhibits rapid, concentration-dependent bactericidal activity against resistant gram-positive bacteria. We studied daptomycin in patients with cSSSIs and septic synovitis.
Methods 47 patients with gram-positive staphylococcal and enterococcal cSSSIs and synovitis were treated with daptomycin at a usual dose of 4 mg/kg daily except in patients with renal compromise when the dose was reduced to 2 mg/kg. In those mixed infections azteonam or amikacin was added for gram-negative rod infection and clindamycon or metronidazole for anaerobes. Treatment lasted from 3 to 26 days.
Results Daptomycin therapy was prematurely discontinued due to drug-induced fever, headache or blurred vision in 3 patients. Of the remaining 44 persons 42 had total resolution of their cSSSIs with antimicrobial therapy and in 29 with concurrent surgical intervention, Five failures were encountered; 3 with septic synovitis due to MRSA and 3 because of adverse drug reactions to daptomycin resulting in abbreviated treatment (one patient had both). Twelve of 47 infections were mixed, 9 with a variety of gram negative rods and 3 due to anaerobes (Prevotella, Bacteroides and Peptostreptococcus spp).
Conclusions Daptomycin is an highly effective bactericidal agent in the management of cSSSIs due to gram-positive pathogens. Of 47 patients including 3 with septic synovitis due to MRSA, 42 had total resolution of their cSSSIs (89%). Twelve of these patients had mixed infection requiring additional simultaneous antimicrobial therapy. Failure of daptomycin in patients with septic synovitis may be due to its large molecular size and high protein binding resulting in limited tissue penetration into joint fluid. Additionally, the drug appears to be free of serious adverse reactions and is more conveniently administered than vancomycin.
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