Macrolactame Antibiotics

Another group of fungus-derived components, sometimes referred to as xenobiotics (Abu-Shakra and Busila 2002, Burkhardt and Kalden 1997, Luger 2001, Robert and Kupper 1999, Yokum 1996), is the macrolactams. Their antibiotic effects seem low compared with their immunologic potential. Similar to cyclosporine, tacrolimus and ascomycin can interfere with calmodulin by distinct binding proteins (Bergmann and Rico 2001, Burkhardt and Kalden 1997, Duddridge and Powell 1997, Furst 1999, Furukawa et al. 1995, Jayne 1999, Kilian et al. 1998, Kurtz et al. 1995, Singer and McCune 1998, Tran et al. 2001, Walker et al. 2002, Warner et al. 1995, Yokum 1996, Yoshimasu et al. 2002). Both drugs are well established within transplantation medicine. In off-label use outside this licensed application, data are so far mainly available on oral and topical tacrolimus and show positive effects on LE activity (Furukawa et al. 1995, Singer and McCune 1998, Tran 2001). However, no clinical data fulfilling the criteria of evidence-based medicine have been published except small studies and case reports (Bergmann and Rico 2001, Duddridge and Powell 1997, Kilian et al. 1998, Walker et al. 2002, Yoshimasu et al. 2002). This applies to many other drugs summarized in this chapter as well. Evidence-based trials are badly needed to compare their effectiveness to classical immunosuppressive regimens like glucocorticosteroids and azathioprine. Another component from this group, called "rapamycin" or "sirolimus", shows a distinctly different mechanism of action and is currently under clinical evaluation for different inflammatory disorders. Based on its promising effects, it may be used for various clinical forms of LE soon (Burkhardt et al. 1997, Singer and McCune 1998, Warner et al. 1995,Yocum 1996).

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