Of vancomycin

Chemistry, biology, and medicine of glycopeptide antibiotics, in particular synthesis of vancomycin 99AG(E)2096. 

Studies on the synthesis of vancomycin and related cyclic peptides 98PAC391. 

Zhn and coworkers have developed SwAr-based macrocyclizadon via biaryl ether formation. The first example of SivAr-based macrocyclizadon for synthesis of model carboxylate-binding pocket C-O-D rings of vancomycin was reported in 1994 fScheme 9.3. ... 

Double intramolecular S Ai reaction leads to a model bicyclic C-O-D-O-E ring, as shown in Eq 9 9 " Synthesis of a model 22-membered AEl-C-0-D ring of vancomycin using similar strategy has been reported Totiil synthesis of vancomycin has been accomplished by Nicolaon and coworkers ... 

The medium is placed in a container having a suitable excess capacity in order to insure the presence of sufficient oxygen and is sterilized by heating at 120°C for about 30 minutes. When cool, the medium is inoculated with about 25 ml of a vegetative inoculum as described above, and the culture is then shaken for about 80 hours at 26°C. The pH of the medium at the beginning of fermentation ranges from about 6.5 to about 7.0 and the final pH is about 7.0 to about 8.0. A fermentation broth thus obtained contained about 180 m9 of vancomycin per ml. 

Vancomycin, ristocetin A and teicoplanin are produced as fermentation products of Streptomyces orientalis, Nocardia lurida and Actinoplanes teichomyceticus, respectively. All three of these related compounds consist of an aglycone basket made up of fused macrocyclic rings and pendant carbohydrate moieties (Fig. 2-1). The macrocycles contain both ether and peptide linkages. The aglycones of vancomycin and teicoplanin contain two chloro-substituted aromatic rings, while the analogous portion of ristocetin A contains no chloro substituents. 

The nurse should administer each IV dose of vancomycin over 60 minutes Too rapid an infusion may result in a sudden and profound fall in blood pressure and shock. When giving the drug IV, the nurse closely monitors the infusion rate and the patient s blood pressure. The nurse reports any decrease in blood pressure or reports of throbbing neck or back pain. These symptoms could indicate a severe adverse reaction referred to as "red neck or "red man syndrome. 9/mptoms of this syndrome include a sudden and profound fall in blood pressure, fever, chills paresthesias and erythema (redness) of the neck and badk. 

Nagarajan R. (1991) Antibacterial activities and modes of action of vancomycin and related giycopeptides. Antimicrob Agents Chemother, 35, 605-609. 

In patients who have received a recent course of vancomycin and/or are critically ill (based on a high APACHE II score)... 

Dexamethasone therapy may reduce antibiotic penetration, so antimicrobial drug dosing may have to be increased (especially vancomycin) to achieve adequate CSF levels. Serum levels of vancomycin should be measured and doses titrated to ensure adequate CNS concentrations. Evaluate whether intraventricular or intrathecal antibiotics are indicated. 

It is important to determine (1) whether the isolate is methicillin-susceptible or methicillin-resistant and (2) whether the patient has a prosthetic valve. For patients with no prosthetic material, methicillin-susceptible staphylococci treatment should consist of a penicillinase-resistant penicillin (e.g., nafcillin or oxacillin) with or without gentamicin, and for methicillin-resistant strains, therapy should consist of vancomycin (see Table 71-4). Combination therapy with aminoglycosides, when used in these patients, typically is given only during the first 3 to 5 days of therapy. In the absence of prosthetic material, some treatment guidelines do not recommend combination therapy against MRSA. However, many clinicians may combine either gentamicin or rifampin with vancomycin if the patient is unresponsive to monotherapy. 

Tediatric dose should not exceed that of a normal adult. dSee Table 71-3 for appropriate dosage of vancomycin. 

What is the risk of overuse of vancomycin in hospitals and what pathogens are becoming problematic ... 

Vancomycin adds broad-spectrum gram-positive coverage, but increasing emergence of vancomycin-resistant organisms (e.g., Enterococcus spp.) prompts conservative use. Thus vancomycin should be included as part of the initial therapy only in the following cases ... 

Figure 3.3 The six apparent ionization constants of vancomycin plotted as a function of weight % methanol. Unfilled circles denote acid groups, and filled circles denote basic groups. Acids usually are indicated by positive slopes and bases, by negative slopes. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis 1996 22 813-818. 

The two most frequently used antibiotics are metronidazole and vancomycin. Metronidazole is recommended as first-line therapy because of the risk of development of vancomycin-resistant enterococci with vancomycin use, as well as its much higher cost. Metronidazole and vancomycin have similar efficacy, though in one study, symptoms resolved sooner with vancomycin [61]. Metronidazole is given orally for 10 days, at a dose of 1 g per day. Vancomycin is given orally for 10 days doses vary from 500 mg/day to 2 g/day. For mild to moderately severe CDAD, low-dose vancomycin is as effective as high-dose vancomycin. Vancomycin use is generally restricted to... 

Tarao K, Ikeda T, Hayashi K, Sakurai I A Successful use of vancomycin hydrochloride in the treatment of lactulose-resistant chronic hepatic encephalopathy. J Gastroenterol Hepatol 1989 4 284-286. 

Dickinson et al. [27], in 1985, published a double-blind controlled trial on the use of oral vancomycin as an adjunctive therapy in acute exacerbations of idiopathic colitis. No significant difference was found between the two treatment groups with only a trend in favor of a superior efficacy of vancomycin. It is important to underline that 7 of the 40 patients enrolled had colonic CD and that none of them had C. difficile infection that could explain the action of vancomycin. Subsequently, intravenous metronidazole, in addition to steroids, was effective similar to placebo in inducing remission [28],... 

The treatment of choice until susceptibility of the organism is known as the combination of vancomycin plus ceftriaxone. Penicillin may be used for drug-susceptible isolates with minimum inhibitory concentrations of 0.06 mcg/mL or less, but for intermediate isolates ceftriaxone is used, and for highly drug-resistant isolates a combination of ceftriaxone and vancomycin should be used. A high percent of S. pneumoniae is either intermediately or highly resistant to penicillin. 

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