Vancomycin reactions

Duffy BL. Vancomycin reaction dnring spinal anaesthesia. Anaesth Intensive Care 2002 30(3) 364-6. 

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 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. 

MANAGING DIARRHEA. Diarrhea may be a sign of a superinfection or pseudomembranous colitis, both of which are adverse reactions tiiat may be seen with the administration of any anti-infective. The nurse checks each stool and reports any changes in color or consistency. When vancomycin is given as part of the treatment for pseudomembranous colitis, it is important to record the color and consistency of each stool to determine the effectiveness of therapy. 

Antibiotics. Antibiotics are commonly administered peroperatively. At the present time, allergy to (3-lactams represents 12-15% of the peroperative reactions observed in France [9]. Vancomycin, which is increasingly used for prophylaxis, has been incriminated in some cases. The red man syndrome is due to non-specific histamine release induced by a rapid intravenous administration [21]. 

The reaction can be carried out efficiently using aryl diazonium tetrafluoroborates with crown ethers, polyethers, or phase transfer catalysts.103 In solvents that can act as halogen atom donors, the radicals react to give aryl halides. Bromotrichloromethane gives aryl bromides, whereas methyl iodide and diiodomethane give iodides.104 The diazonium ions can also be generated by in situ methods. Under these conditions bromoform and bromotrichloromethane have been used as bromine donors and carbon tetrachloride is the best chlorine donor.105 This method was used successfully for a challenging chlorodeamination in the vancomycin system. 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

CS, a 55-year-old woman, is admitted to the hospital with an intraabdominal infection. During the patient interview, CS states that she is allergic to aspirin, codeine, sulfa drugs, penicillin, levofloxacin, and vancomycin. The reactions are described as follows ... 

Correct timing of antibiotic administration is imperative to preventing SSI. The National Surgical Infection Prevention Project recommends infusing antimicrobials for surgical prophylaxis within 60 minutes of the first incision. Exceptions to this rule are fluoroquinolones and vancomycin, which can be infused 120 minutes prior to avoid infusion-related reactions.1 No consensus has been reached on whether the infusion should be complete prior to the first incision. However, if a proximal tourniquet is used, antibiotic administration should be complete prior to inflation. 

Verify the patient s allergy history and the type of reaction experienced. Attempt to discern between true allergy and adverse event. (3-Lactam-allergic patients may receive clindamycin, vancomycin, or other antimicrobials. Crossreactivity between penicillin allergy and cephalosporins is low but cephalosporins should be avoided in patients with a history of anaphylaxis to penicillins. 

Vancomycin is effective and is the drug of choice for the patient with a history of immediate-type hypersensitivity reaction to penicillin. When vancomycin is used, the addition of gentamicin is not recommended. 

Penicillin G 24 million units/24 h IV in four to six equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory concentration 0,1 mcg/mL) and does not produce /5-lactamase vancomycin should be used in patients with immediate-type hypersensitivity reactions to beta-lactam antibiotics (see Table 37-3 for dosing guidelines) cefazolin may be substituted for nafcillin or oxacillin in patients with non-immediate-type hypersensitivity reactions to penicillins... 

In penicillin-allergic patients, oral or parenteral clindamycin may be used. Alternatively, a first-generation cephalosporin such as cefazolin (1 to 2 g IV every 6 to 8 hours) may be used cautiously for patients who have not experienced immediate or anaphylactic penicillin reactions and are penicillin skin test negative. In severe cases in which cephalosporins cannot be used because of documented methicillin resistance or severe allergic reactions to /1-lactam antibiotics, IV vancomycin should be administered. 

Carboxylic acid-terminated organosilanes were used in the early studies on chemically bonded glycopeptides to immobilize vancomycin and thiostrepton via then-amino groups, leading to the formation of stable amide bonds between antibiotics and modified silica [7]. In a typical reaction, 4 g of dry silica gel is slurried on 50 mL of dry toluene. Two grams of [l-(carbomethoxy)ethyl]methyldichlorosilane or [2-(carbomethoxy)ethyl]trichlorosilane is dissolved in 15 mL of dry toluene contained in a dropping flask. The organosilane solution is added dropwise over 30 min... 

In a typical reaction, the macrocycle is treated with a 2-3 M excess of (3-isocyanatopropyl)triethoxysilane in dry DMF. The derivative is then added to a dry DMF slurry of silica gel ( 2 g of functionalized selector to 4 g of silica gel). The solution is stirred, allowed to react for 20 h at 107°C, and then cooled, filtered, and washed with methanol, 50% aqueous methanol, and methanol again, and finally dried. Surface coverage data are reported only in the case of the commercially available vancomycin CSP (see Table 2.2), immobilized by joining on average three linkers per vancomycin molecule, probably via a 3-isocyanatopropyl-silane [48]. 

Recently, the semi-synthesis of Vancomycin (48) on solid supports was accomplished using an allylic linker (Scheme 3.2) [123, 124]. Polymer-bound chiral electrophilic selenium reagents have been developed and applied to stereoselective se-lenylation reactions of various alkenes (Tab. 3.9) [125]. 

Many other reactions have been used to construct macrocycles, and many are related to specific bond formations and therefore not very widely applicable. Since bisaryl ethers and biphenyl units are relatively common in naturally occurring macrocycles [4] (both units can be found in the important antibiotic vancomycin, 20, Fig. 7), some approaches to their synthesis will... 

Recently, the piperazine intermediate 15 for the total synthesis of (—)-lemon-omycin (9) was reported by Fukuyama et al. [14], (—)-Lemonomycin possesses interesting antibiotic activity against methiciUin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, as well as cytotoxicity against the human colon tumor cell line HCT-116 [15]. The reaction of 2-isocyanoethyl phenyl carbonate 11 gave Ugi product 14, which was further transformed to a piperazine intermediate 15 (Scheme 2). 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

Local treatment of skin and soft tissue infections with antibiotic-containing ointments or solutions should not be used because it leads to allergic reactions and rapid development of bacterial resistance. In settings where MRSA or resistant Enterobacte-riaceae (like ESBL s gram negative bacteria with extended spectrum beta lactames) or Pseudomonas spp. occur, the empiric use of vancomycin and a carbapenem can be necessary. The risk of transmission of these organisms should be minimalised by hygienic and isolation measures. 

The synthesis of jS-hydoxy-a-amino acids is important since these compounds are incorporated into the backbone of a wide range of antibiotics and cyclopeptides such as vancomycins. These highly functional compounds are also subject to dynamic kinetic resolution (DKR) processes, as the stereocenter already present in the substrate epimerizes under the reaction conditions and hence total conversions into single enantiomers are possible. These transformations can be iy -selective ° for N-protected derivatives as shown in Figure 1.27 when using a mthenium-BlNAP catalyzed system and anfi-selective when the jS-keto-a-amino acid hydrochloride salts are reduced by the iridium-MeOBlPHEP catalyst as shown in Figure 1.28. One drawback is that both these reductions use 100 atm hydrogen pressure. 

Phenylglycine derivatives are key intermediates in the synthesis of vancomycin. 81-85 This amino add is also very useful for incorporation into oxazolidinones as a chiral aux-iliaryt45,47 48 53 86 87 and for modulating bioactivities of peptides and peptidomimeticsJ85,88 There are several possible approaches to the synthesis of phenylglycines, including the Strecker reaction and the Evans electrophilic azidation reaction.181 ... 

Table 4 lists some representative examples of macrocyclization via the intramolecular SNAr reaction. In addition to the 14- and 17-membered cycloisodityrosines shown in the table, a variety of mono-, bi-, and tricyclic systems from the vancomycin family of natural products including the orienticin C/40 vancomycin J44-47 and teicoplanin[48 aglycons have been prepared by this method.This versatility, coupled with the high yields obtained, makes the intramolecular SNAr reaction currently the most widely applicable method for cycloisodi-tyrosine formation. 

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