Can Daptomycin Have An Impact With Skin And Skin Structure Infections?

Author(s): 
By Gerard Guerin, DPM, CWS

Spectrum Of Activity: What Does Daptomycin Offer?
Daptomycin is the first antibiotic in a new class called the cyclic lipopeptides. Daptomycin binds to and depolarizes the cytoplasmic membrane of gram-positive bacteria, ultimately causing rapid cell death.10 It was approved in 2003 in the U.S. for the treatment of complicated SSSIs caused by S. aureus, including MRSA, as well as Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only). Recently, the label for daptomycin was extended to include the treatment of bacteremia, including right-sided endocarditis caused by S. aureus.11

Daptomycin provides dose-dependent bactericidal activity against a wide range of aerobic and anaerobic gram-positive isolates (including multiresistant strains).12,13 In addition, it has demonstrated in vitro activity against methicillin-susceptible S. aureus (MSSA), MRSA and anaerobic gram-positive organisms (such as Finegoldia magna and Peptoniphilus asaccharolyticus) cultured from diabetic foot infections.13 Furthermore, an in vitro study demonstrated that 96 percent of 105 strains of S. aureus with reduced susceptibility to vancomycin, including VISA, were susceptible to daptomycin.14

What The Literature Reveals About Daptomycin
In two multicenter, randomized phase 3 clinical trials, researchers compared daptomycin with standard therapy (penicillinase-resistant penicillins or vancomycin) in 1,092 patients with complicated SSSI and most of these were caused by S. aureus.15 The treatment duration was seven to 14 days. Researchers defined clinical success as the resolution of signs and symptoms to the point where antibiotic therapy is no longer required. They assessed clinical success six to 20 days after the last dose. These studies showed that clinical success rates were statistically comparable (“noninferior”) between those patients clinically evaluable in the daptomycin and comparator groups (83 percent versus 84 percent respectively).15 In the MRSA subpopulation, clinical success rates were 75 percent and 69 percent respectively for patients treated with daptomycin and vancomycin.15

Daptomycin’s efficacy against other gram-positive pathogens (streptococci and enterococci) was also comparable to that of standard therapy.15 Patients receiving daptomycin had fewer days of therapy as 63 percent of these patients required four to seven days of therapy in comparison to 33 percent of patients in the comparator group.15 A post hoc analysis of the data from 103 clinically evaluable patients who had diabetic foot infections demonstrated that daptomycin was as effective as vancomycin or penicillinase-resistant penicillins in treating gram-positive infections.16 Bear in mind that the number of MRSA isolates in this subpopulation was modest with only one MRSA isolate in the daptomycin-treated group.

With all new antibiotics, there is concern about resistance but daptomycin resistance rates to S. aureus and other gram-positive cocci are low in vitro.17 In a few instances, MRSA isolates have been reported to have become nonsusceptible to daptomycin in vivo during treatment for bacteremia, endocarditis or osteomyelitis.18 Nonsusceptible isolates have not yet been reported in patients with complicated SSSI who received daptomycin treatment.18

Daptomycin was well tolerated in these trials of patients with complicated SSSIs, and the frequency, distribution and severity of adverse events were similar between daptomycin and comparator drugs.15 For example, 2.2 percent of patients treated with daptomycin experienced renal failure in comparison to 2.7 percent of patients in the comparator group.15 The prevalence of adverse events was similarly small and comparable between treatment groups among those patients who had diabetic ulcer infections.16 In contrast, a recent phase 3 trial of daptomycin 6 mg/kg for the treatment of S. aureus bacteremia found significantly more patients had renal impairment with standard therapy (antistaphylococcal penicillin or vancomycin) (18 percent) than with daptomycin (7 percent).19

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