Cephalosporins cefuroxime

Another important enzymatic process in the production of 7-ADCA, for use in the production of semi-synthetic cephalosporins, is the hydrolysis of 7-aminocephalosporanic add (7-ACA) by the enzyme acetyl esterase. This process, again using immobilisation techniques, is illustrated in Figure 6.16. Hie deacylated product can be used, for example, as an intermediate in the production of the important oral cephalosporin cefuroxime. We will return to cephalosporin antibiotics later in this chapter. 

Uncomplicated exacerbation Not requiring hospitalization Less than 3 exacerbations per year No comorbid illness I I V, greater than 50% predicted No recent antibiotic therapy Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis Oral Macrolide (azithromycin, clarithromycin) Second- or third-generation cephalosporin (cefuroxime, cefpodoxime, cefdinir, cefprozil) Doxycycline Ketolide (telithromycin) P-Lactam/P-Iactamase inhibitor (amoxicillin-clavulanate) Intravenous Not recommended... 

Complicated exacerbation FEV, less than 50% predicted Comorbid cardiac disease Greater than or equal to 3 exacerbations per year Antibiotic therapy in the previous 3 months Above organisms plus drug-resistant pneumococci, P-lactamase-producing H. influenzae and M. catarrhalis, Escherichia coli, Proteus spp., Enterobacter spp., Klebsiella pneumoniae Oral P-Lactam/P-Iactamase inhibitor (amoxicil 1 i n-clavulanate) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) Intravenous P-Iactam/P-Iactamase inhibitor (ampicillin-sulbactam) Second- or third-generation cephalosporin (cefuroxime, ceftriaxone) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, moxifloxacin)... 

See section on treatment of bacterial pneumonia. Macrolide/azalide erythromycin, clarithromycin, azithromycin. cTetracydine tetracycline hydrochloride, doxycydine. Cephalosporin cefuroxime, ceftriaxone, cefotaxime. eCarbapenem imipenem-cilastatin, meropenem. Fluoroquinolone ciprofloxacin, gatifloxacin, or levofloxacin. 

Second-generation cephalosporins (cefuroxime, cefamandole, cefoxitin, cefotetan, cefaclor, and others) are characterized by high activity with respect to Gram-positive microorganisms that are resistant to beta-lactamase action. They do not have a noticible effect on enterococci. 

Cephalosporins are -lactam antibiotics that block microbial cell wall synthesis. The original cephalosporin. Cephalosporin C, has only weak antibiotic activity. Therefore much more powerful second generation cephalosporins were developed by side-chain modification. Modifications at Cl are most effective but modifications at position 3 are also important so as to increase in vivo activity. Synthesis of the second generation cephalosporin cefuroxime requires the replacement of the C3 acetoxy side-chain of the precursor with a caibamate group. Chemical methods proceed via a hydroxylated intermediate which causes problems due to a tendency to lactonise at low pHs. Therefore development of a biocatalysis step was initiated in order to achieve selective reaction nnder mild conditions. 

First-generation cephalosporins cefazolin for parenteral administration cefadroxil or cephalexin for oral administration. Second-generation cephalosporins cefuroxime for parenteral administration cefaclor, cefuroxime axetil, cefprozil, for oral administration. Third-generation cephalosporins ceftazidime, cefotaxime, ceftriaxone for parenteral administration cefixime, cefpodoxime, ceftibuten, cefdinir, cefditoren for oral administration. Fourth-generation cephalosporin cefepime for parenteral administration. Cephamycins cefoxitin and cefotetan for parenteral administration. 

An additional example of lactone hydrolysis includes the API lovastatin (9). In addition to lactone cleavage reactions, lactone formation can also occur as in the case of the API cephalosporin cefuroxime sodium (Fig. 4) (10). 

Cephalosporin cefuroxime, ceftriaxone, cefotaxime. Carbapenem imipenem-cilastatin, meropenem. 

For infections developing more than 36 to 48 hours after the bite, the risk of P. multocida being involved decreases dramatically. In these patients, staphylococci or streptococci are the most likely causative pathogens. Therapy in this instance includes a penicillinase-resistant penicillin (dicloxacillin 250-500 mg orally four times daily in children, 25-50 mg/kg per day oraUy divided into four doses) or a cephalosporin (cefuroxime axetil 500 mg orally twice daily in children, 20-30 mg/kg per day orally divided into two doses) and should be given for a full 10 to 14 days. ... 

During the research programme of the Fujisawa Pharm. Co. in Japan interesting new monocyclic -lactams (239) have been isolated from Nocardia tsuyama-nensis ATCC 21806 [208]. This biosynthetic lactam antibiotic exists as cis and trans oximes (nocardicin A and B) and is unique from the point of view that it contains an unfused -lactam system, a side-chain not previously found in biosynthetic lactam antibiotics. However, a new Glaxo cephalosporin, Cefuroxime, contains a side-chain siniilar to that in (239) [209]. 

Hybridization of the side chains of two second-generation cephalosporins (cefuroxime and cefotiam) resulted in a series of new derivatives that showed a quantum jump in in vitro activity. Cefotaxime is the first of this new class of third-generation cephalosporins, which now includes a number of analogs undergoing clinical evaluation. It remains to be seen whether or not the potent in vitro activity of these new compounds will result in significant clinical advantages over existing cephalosporins. 

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