Daptomycin clinical studies

If the isolate is determined to be vancomycin-resistant, it is most important to know the exact species because some of the treatment options, such as quinupristin/dalfopristin, are not active against E. faecalis. Currently, the treatment options for vancomycin-resistant enterococci (VRE) are not well established by clinical studies or patient experience. The treatment recommendations for vancomycin-resistant E. faecium include linezolid or quinupristin/dalfopristin for a minimum of 8 weeks. However, newer agents, such as daptomycin, may provide another option for treatment for either enterococci species (E. faecium and E. faecalis). Additionally, guidelines suggest the use of imipenem-cilistatin plus ampicillin or ceftriaxone plus ampicillin for the treatment of E. faecalis with a minimum of 8 weeks of therapy. Consultation with an infectious diseases specialist is recommended. 

Lilly conducted Phase I and Phase II clinical studies on daptomycin in the 1980s and early 1990s for skin and soft tissue infections, bacteraemia and endocarditis.9 In a Phase I safety study to evaluate increasing the dose to 4 mg/kg every 12 hours to treat endocarditis, two of five volunteers exhibited symptoms of muscle toxicity, including elevated creatine phosphokinase (CPK). After observing muscle toxicity with this dosing regimen, Lilly discontinued clinical development of daptomycin in 1991. 

The polymyxin program did not proceed into the clinic but translatability was still addressed using samples from patients treated with a variety of standard of care antibiotics (piperacilhn/tazobactam, vancomycin, penicillin V, tobramycin, gentamicin, ampicillin, cefuroxime, clindomycin, clarithromycin, cefepime, daptomycin IV, bumetanide, vibramycin, and cyclophosphamide) compared to samples from healthy volunteers. This sample set was analyzed for sCr, BUN, urinary total protein, and urinary microalbumin as well as the emerging biomarkers urinary KIM-1, urinary NGAL, and urinary NAG. Much like the large animal studies with polymyxin B, the response for the antibiotic-treated cohort produced increases in all urinary- and serum-based... 

Observational studies Clinical experience of daptomycin for Gram-positive infections (skin and soft tissue infections, bacteremia. 

The ability to block the amino function of Om, then deacylate the t BOC prO tected nucleus, has facilitated the development of many A21978C analogs containing modifications at the N>terminal Trp. Semisynthetic derivatives containing novel fatty acyl, aroyl, and extended peptide side chains were readily deblocked by trifluoroacetic acid treatment (3). Subsequent biological studies identified the n>decanoyt derivative, daptomycin, as a candidate for clinical development (see Section IV). 

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