Aminoglycosides glycopeptides

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Classes of antibiotics L P-lactam, T tetracycline, M macrolide, S sulphonamide, Ap amphenicol, A aminoglycosides, G glycopeptides, Q quinolone... 

Table 14.1 Suggested reference ranges for serum levels of aminoglycoside and glycopeptide antibiotics...

Staphylococcus aureus - [ANTIBIOTICS - BETA-LACTAMS - CEPHALOSPORINS] (Vol 3) - [DISINFECTANTS AND ANTISEPTICS] (Vol 8) - [ANTIBIOTICS - BETA-LACTAMS - BETA-LACTAMASE INHIBITORS] (Vol 3) - [ANTIBIOTICS - LINCOSAMINIDES] (Vol3) - [ANTIBIOTICS - BETA-LACTAMS - PENICILLINS AND OTHERS] (Vol 3) - [ANTIBIOTICS-AMINOGLYCOSIDES] (Vol2) - [ANTIBIOTICS - GLYCOPEPTIDES(DALBAHEPTIDES)] (Vol 2) -bacitracin resistance [ANTIBIOTICS - PEPTIDES] (Vol 3) -ethanol activity against [DISINFECTANTS AND ANTISEPTICS] (Vol 8) -inhibited by sorbates [SORBIC ACID] (Vol 22)... 

Teicoplanin can be nephrotoxic, but less often than vancomycin (6). However, concomitant aminoglycoside therapy in some patients makes the contribution of the glycopeptide antibiotic difficult to assess. Renal toxicity was observed more often in patients receiving the combination of netilmicin plus vancomycin than in patients treated with netilmicin plus teicoplanin (35). Similar differences in nephrotoxicity between vancomycin and... 

The role of enterococci in nosocomial infections is probably due to a variety of factors of which antimicrobial resistance appears to be a primary cause. Enterococci possess a broad spectrum of both natural (intrinsic) resistance and acquired (transferable) resistance (Franz et al. 2003). Examples of antibiotics to which the enterococci present an intrinsic resistance include the P-lactam antibiotics (third generation cephalosporins), sulphonamides and clindamycin and aminoglycosides in low levels (Eranz et al. 2003). Acquired resistance based on plasmids or transpo-sons acquisition has relevance for chloramphenicol, erythromycin, high levels of clindamycin, aminoglycosides, tetracycline, high levels of P-lactam antibiotics, fluoroquinolones and glycopeptides like vancomycin (Murray 1990 Leclercq 1997). In particular, vancomycin-resistant enterococci (VRE) pose a major problem... 

An intervening chapter delineates the enzymatic basis for the bacterial resistance to five classes of antibiotics the /3-lactams (e.g., penicillin), the glycopeptides (e.g., vancomycin), the aminoglycosides (e.g., streptomycin), the macrolides (e.g., erythromycin), and the quinolones (e.g., ciprofloxacin). The classes represent the major antibiotics used clinically today. Starting with the /3-lactams and ending with the fluoroquinolones, the authors discuss the mechanisms and molecular basis for resistance, and show how resistance is not a matter of if, but when. 

The dithiasuccinyl protection group was developed by Barany and Merrifield for use in peptide synthesis, though nowadays, it is more often deployed in aminoglycoside and glycopeptide synthesis. In peptide synthesis, the Dts group survives the stron y acidic conditions required to cleave /err-butyl and benzyl esters and carbamates. 

Nowadays, antibiotics are primarily classified according to the mechanism of their action, with similarity of chemical structure as a secondary factor. Penicillin and its derivatives inhibit the formation of bacterial cell walls (Fig. 3.38). Cephalosporins have the same active mechanism. Other compounds are taken up into bacterial DNA to form unstable molecules (quinolones, metronidazole) or inhibit peptide synthesis (tetracychnes, aminoglycosides, macrolides). Some antibiotics (e.g. glycopeptides) exert a complex effect. 

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