Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections
Status:
Completed
Trial end date:
2008-05-01
Target enrollment:
Participant gender:
Summary
Daptomycin is a new antimicrobial agent which has activity against resistant Gram positive
cocci including MRSA. The phase 3 clinical trials for skin and soft tissue infections (SSTI)
with Staphylococci and Streptococci have already demonstrated that daptomycin was noninferior
to the comparator agent (vancomycin or beta-lactams) (10). Although this clinical trial did
not include any patients with clostridial infection, there is in vitro data to support the
activity of daptomycin against a variety of clostridial species(11) ( Clostridium
perfringens) Therefore, for this trial we will include patients with clostridial infections
with this species. Additionally, the patients in the SSTI study were not as ill as the
proposed study population. Therefore for treatment of such severe infections, we would like
to use a higher dose of daptomycin (6mg/kg/dose). The reasons for using a higher dose of
daptomycin in this subgroup are as follows:
1. Patients who are severely ill have an increased volume of distribution; and therefore
have a lower serum concentration of daptomycin. These patients might require a higher
dose of daptomycin to achieve the desired serum concentration.
2. One of the organisms involved in necrotizing fasciitis is enterococcus (both-fecalis and
faecium). E.faecium has higher MICs to daptomycin and would require a higher dose of the
drug to achieve adequate free (unbound) serum concentration of the drug.
3. Both necrotizing fasciitis and endocarditis are serious deep seated infections. The
clinical trials for endocarditis are using 6mg/kg/dose of daptomycin.
Therefore for optimal treatment of necrotizing fasciitis, it is justifiable that we should
use the higher dose of daptomycin.
Objective:
To evaluate the clinical and microbiological efficacy and safety of higher dose daptomycin
therapy in the treatment of patients with severe necrotizing skin and soft tissue infections.
Type of Study:
Open label, single center study.
Phase:
N/A
Details
Lead Sponsor:
University of Maryland University of Maryland, Baltimore