Antibiotics vancomycin and teicoplanin

Two EPMEs based on macrocyclic glycopeptide antibiotics—vancomycin and teicoplanin—were designed for the assay of acetyl-L-carnitine [44]. The linear concentration ranges for the proposed electrodes were 10 5-10-2 mol/L for the vancomycin-based electrode and 10 4-10-2 mol/L for the teicoplanin-based electrode, with slopes of 58.1 and 55.0mV/p(acetyl-L-camitine), respectively. The enantioselectivity was determined over D-carnitine. 

Three EPMEs based on macrocyclic glycopeptide antibiotics— vancomycin and teicoplanin (modified or not with acetonitrile)—were proposed for the determination of l- and D-enantiomers of methotrexate (Mtx) [48]. The linear concentration ranges for the proposed enantioselective membrane electrodes were between 10 6 and 10-3 mol/L for l- and D-Mtx. The slopes of the electrodes were 58.00 mV/pL-Mtx for vancomycin-based electrode, 57.60 mV/pD-Mtx for teicoplanin-based electrode and 55.40 mV/pD-Mtx for teicoplanin modified with acetonitrile-based electrode. The detection limits of the proposed electrodes were of 10 8 mol/L magnitude order. All proposed electrodes proved to be successful for the determination of the enantiopurity of Mtx as raw material and of its pharmaceutical formulations (tablets and injections). 

Acquired resistance to the glycopeptides is transposon-mediated and has so far been largely confined to the enterococci. This has been a problem clinically because many of these strains have been resistant to all other antibiotics and were thus effectively untreatable. Fortunately, the enterococci are not particularly pathogenic and infections have been confined largely to seriously ill, long-term hospital patients. Two types of acquired glycopeptide resistance have been described (Woodford et al. 1995). The VanA phenotype is resistant to vancomycin and teicoplanin, whereas VanB is resistant... 

Brush-type, proteins, CDs, natural molecular imprint-based polymers (MIP), and macrocyclic antibiotics have been immobilized as chiral selectors on packed-CEC columns. Zheng and Shamsi demonstrated the possibility of using chiral CEC—ESI/MS with a commercially packed column for the determination of warfarin enantiomers in human plasma using coumachlor as an internal standard (IS). Robustness of this chiral CEC capillary was recently improved by a novel procedure and applied for the simultaneous enantiosepara-tion of height /1-blockers with multimodal CSP using different combinations of vancomycin and teicoplanin, as presented in Figure 5. ... 

Vancomycin and teicoplanin display excellent activity against staphylococci and streptococci, but because of the wide availability of equally effective and less toxic drugs, they are second-line drugs in the treatment of most infections. As antistaphylococcal agents they are less effective than 3-lactam cephalosporin antibiotics, such as nafciUin and cefazoUn. They have attained much wider use in recent years as a consequence of the emergence of methicUlin-resistant S. aureus (MRSA) infections, in particular the growing importance of Staphylococcus epidermidis infections associated with the use of intravascular catheters and in patients with peritonitis who are on continuous ambulatory peritoneal dialysis. 

Thiostrepton is a macrocyclic polypeptide antibiotic that is structurally different from vancomycin and teicoplanin. It is soluble in water and acetic acid. It is obtained from Streptomyces azureus bacterium. There are 17 chiral centers in this antibiotic, with 2 large cavities (A and B in Fig. 1). Five thiazole rings, 1 quinoline ring, 5 hydroxyl groups, 10 amide linkages, and 1 secondary amine make the molecule stereo-specific in nature. 

In addition to the common use of vancomycin and teicoplanin, the use of other antibiotics as chiral selectors in HPLC were limited. Only a few reports are available in the literature dealing with these antibiotics as HPLC CSPs. Armstrong et al. [42] resolved about 230 racemates on the ristocetin A antibiotic covalently bonded to silica gel. The resolution was carried out using the three modes of mobile phases. The results were complimentary to those obtained on vancomycin and teicoplanin CSPs. In another study, the effect of selector coverage and mobile phase composition on enantiomeric resolution with ristocetin A CSP was carried out by Armstrong et al. [43]. Thiostrepton-based CSP was also used to resolve the enantiomers of thioridazine, 2,2,2-trifluoro-l-... 

The antibiotics employed as CSPs generally have macrocyclic structures. These molecules are relatively large and contain several chiral centers and cavities that exhibit enantioselectivity via inclusion-complexation interactions with analytes. Antibiotics have been known to display a broad degree of enantioselectivity [149-153], Vancomycin and teicoplanin are the most widely employed antibiotics for this use. Karlsson et al. [154] used a vancomycin CSP in both polar organic mode and reverse-phase CEC to separate a variety of enantiomers (Table 3). 

The SARs of glycopeptide antibiotics have mostly been studied with vancomycin and teicoplanin. Some other examples also comprise the glycopeptides eremomycin, baMmycin, ristocetin, and avoparcin. The reasons for the predominance of vancomycin and teicoplanin are that, particularly vancomycin (Vancomycin, Eli Lilly and Company) and teicoplanin (Targocid, Lepetit, Italy), are industrial large-scale fermentation products, and most of these studies were performed within research programs or with the participation of researchers from Eli Lilly and Lepetit. 

In addition to the vancomycin and teicoplanin CSPs, ristocetin A (Chirobiotic R) [289] and recently avoparcin [280] have been evaluated as novel chiral SOs and CSPs. It turned out that within the large family of macrocyclic antibiotics complementarity of enantioselectivity exists for different glycopeptides. As a consequence, very often it is possible to obtain a complete resolution by switching to a congeneric antibiotic CSP, if after optimization no baseline, but partial. separation can be achieved on a certain macrocyclic antibiotic type CSP (see Fig. 9.22). It can be expected that the enantioselectivity potential of closely related antibiotics will be further exploited in the future leading to an increase in the number of macrocyclic antibiotic type CSPs. 

Vancomycin and teicoplanin are complex cyclic glycopeptide antibiotics (O Fig. 11). Although the structures of these compounds were elucidated decades ago, total s)mtheses of vancomycin aglycone [150,151,152,153,154,155], fully glycosylated vancomycin [156], and teicoplanin [157,158] have only recently been reported. 

Vancomycin was discovered in the 1950s in a soil sample collected in the jungle of Borneo and isolated by Eli Lilly from culture broth of the actinomycete Streptomyces orientalis, which was later named Nocardia orientalis and finally Amycolatopsis orientalis. It was first used in clinics in 1959, and today also teicoplanin (O Fig. 25) is being used clinically. The other gly-copeptides of the vancomycin group such as ristocetin A (O Fig. 26) have too many toxic side effects to be used as a therapeutic. Vancomycin and teicoplanin are among the last antibiotics... 

Antibiotic resistance behaviour of 308 enterococci isolated from Bryndza cheese is shown in Fig. 5. All enterococcal isolates from Bryndza cheese were susceptible to ampicillin, streptomycin, gentamicin, vancomycin, and teicoplanin. For these same isolates, resistance rates to rifampicin, erythromycin, ciprofloxacin, and... 

Figures 6-8 illustrate antibiotic resistance patterns of E. faecium, E. faecalis, and E. durans isolates from Bryndza cheese. No one of the E. faecium, E. durans, and E. faecalis isolates were resistant to ampicillin, streptomycin, gentamicin, vancomycin, and teicoplanin. Thirty six percent of the E. faecium isolates and 22% of the E. faecalis isolates were resistant to erythromycin. E. faecium showed similar resistance to rifampicin (31%) as E. faecalis (29%). Both E. faecium and E. faecalis strains exhibited the same resistance to ciprofloxacin (2%). E. durans isolates showed very low level of resistance to rifampicin, erythromycin, ciprofloxacin, and nitrofurantoin (1 %). E. faecium, E. faecalis and E. durans were also found to be the predominant species recovered from naturally ripened European cheeses and...

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