AbstractBecause of the dramatic increase in severe infections caused methicillin-resistant Staphylococcus aureus (MRSA), including skin and skin structure infections (SSSI), and reports of vancomycin failures in the treatment of these infections, agents with better activity against MRSA are clearly needed. Daptomycin, the first cyclic lipopeptide, exerts its concentration dependent bactericidal activity against S. aureus through a calcium dependent formation of channels leading to disruption of the bacterial cell membrane potential. Daptomycin is 90% protein bound, has a half-life of 8–9 h, is eliminated through renal excretion, and has a good penetration into inflammatory skin blisters. This compound was shown to be non-inferior to the comparator in two double-blind randomized phase III studies including patients with complicated SSSI, using a dose of 4 mg/kg/day. In these studies, cure rates in the clinical and microbiology evaluable populations were 83.4% and 84.2% (95% CI, -4 to 5.6), and 84.7% and 85.9% (95% CI, -3.8 to 6.3) for daptomycin and comparator, respectively. Daptomycin also showed efficacy in prospective studies in patients with infective cellulitis or erysipelas, necrotizing soft tissue infection, and infected diabetic foot ulcers. Even though the standard dose of 4 mg/kg/day is considered appropriate for most SSSI, higher doses (e.g. 6 to 10 mg/kg/day) are currently suggested for patients with sepsis, necrotizing infection, prior glycopeptide failure, infections caused by vancomycin intermediate S. aureus (VISA) strains, renal insufficiency, burns, and in intravenous drug users. Overall, daptomycin is considered a well tolerated antibiotic. In clinical trials, drug discontinuation rate has been similar in patients receiving daptomycin compared with those treated with the comparators; however, muscular damage associated with increased serum creatine phopshokinase levels occurs in about 3% and 7% of the patients treated with 4 and 6 mg/kg/day, respectively. This reversible muscle toxicity appears to correlate with the daptomycin trough concentration and time of exposure.

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