Daptomycin

Fig. 10. Stmcture of daptomycin where L-Kyn is L-kynurenine and (h-threo) 3-MeGlu is L-// fi (9-3-methylglutamic acid.

CA-MRSA is susceptible to more antibiotics than HA-MRSA. Like HA-MRSA, CA-MRSA typically is sensitive to vancomycin, linezolid, daptomycin, tigecycline, and quinupristin/ dalfopristin, but it also may be sensitive to clindamycin, doxy-cycline, minocycline, and/or trimethoprim-sulfamethoxazole (TMP-SMX).14... 

Linezolid 600 mg by mouth every 12 hours Vancomycin 1 g IV every 12 hours Daptomycin 4 mg/kg IV daily CA-MRSA suspected ... 

Regimen should include vancomycin, daptomycin, quinupristin/ dalfopristin or linezolid. ... 

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. 

Methicillin-resistant Staphylococcus aureus (MRSA) is a common hospital-acquired pathogen and is also increasing in the community. MRSA has presented a problem in the past because it required treatment with vancomycin. Community-acquired MRSA presents a major therapeutic challenge. MRSA can cause pneumonia, cellulitis, and other infections. Clinicians should be aware of the rate of hospital and community MRSA in your geographic area. New treatment options are available for MRSA. They include linezolid, tigecycline, and daptomycin. Prospective clinical trials have not demonstrated benefits of these agents over vancomycin.36-37... 

Figure 11.5 Amino acid building blocks are incorporated into daptomycin backbone successively by NRPS subunits DptA, DptBC and DptD (a). Structural diversity of daptomycin peptide core can be obtained by genetic modifications of dpt gene cluster (b). C, condensation domain A, adenylation domain PCP, peptidyl carrier protein E, epimerase TE, thioesterase domain... 

Baltz, R.H., Miao, V. and Wrigley, S.K. (2005) Natural products to drugs daptomycin and related lipopeptide antibiotics. Natural Product Reports, 22, 717. 

Miao, V., Coeffet-Le Gal M.-F. et al. (2005) Daptomycin biosynthesis in Streptomyces roseosporus cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology (Reading, England), 151,1507. 

Coeffet-Le Gal, M.F., Thurston, L., Rich, P. et al. (2006) Complementation of daptomycin dpt A and dptD deletion mutations in trans and production of hybrid lipopeptide antibiotics. Microbiology (Reading, England), 152,2993. 

Gu, J.Q., Nguyen, K.T., Gandhi, C. et al. (2007) Structural characterization of daptomycin analogues A21978C1 3(D-Asn11) produced by a recombinant Streptomyces roseosporus strain. Journal of Natural Products, 70, 233. 

Nguyen, K.T., Ritz, D., Gu, J.-Q. et al. (2006) Combinatorial biosynthesis of novel antibiotics related to daptomycin. Proceedings of the National Academy of Sciences of the United States of America, 103, 17462. 

Grunewald, J., Sieber, S.A., Mahlert, C. et al. (2004) Synthesis and derivatization of daptomycin a chemoenzy-matic route to acidic lipopeptide antibiotics. Journal of the American Chemical Society, 126, 17025. 

Kopp, F., Grunewald, J., Mahlert, C. and Marahiel, M.A. (2006) Chemoenzymatic design of acidic lipopeptide hybrids new insights into the structure-activity relationship of daptomycin and A54145FNR Biochemistry, 45, 10474. 

One of the most characteristic features of FRET is its sensitive dependency on the fluorophore distance. This is advantageously used to evaluate structures and conformational changes of peptides, glycopeptides, and proteins among other molecules [164-166], The conformational change of the lipopeptide antibiotic daptomycin from an inactive linear form to a biological active cyclic form... 

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