Chapter 11. Antibiotics

Publisher Summary The search for new antibiotics afforded a number of new activities. Various studies forecast the potential benefits for the use of antibiotics in combination. This chapter discusses those antibiotics that show antibacterial activities and includes a very limited section on β-lactam antibiotics. Reports on new microbially produced β-lactam antibiotics includes compounds like N-acetyl thienamycin from Streptomyces cattleya , three compounds from Streptomyces olivaceus , and four epithienamycins from Streptomyces flavogriseus . The epithienamycins showed antimicrobial activities and β-lactamase susceptibilities that vary widely among each other. Clinical effort on new amino cyclitol antibiotics appears to center on drugs like netilmicin and 1-N-ethylsisomicin, which is active against some of the gentamicin-resistant organisms. In pharmacological studies, netilmicin appear to produce more predictable blood levels. Also synthetic modifications of gentamicin and kanamycin afforded a number of active compounds. Such compounds have greatly enhanced the antimicrobial activity, but their toxicities are correspondingly higher. A novel approach to aminocyclitol modification sequenced the use of inactivating enzymes with synthetic organic procedures. An enzyme from Pssudomonas aeruginosa GN573 is used in the presence of ATP and MgSO 4 to phosphorylate kanamycin B specifically at the 3' position. Treatment with silylating agents gave the chloride that is subsequently hydrogenated to give kanamycin B.