Cefuroxime activity

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

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)... 

If treatment failure occurs with amoxicillin, an agent should be chosen with activity against /1-lactamase-producing H. influenzae and M. catar-rhalis as well as drug-resistant S. pneumoniae (such as high-dose amoxicil-lin-clavulanate (recommended), or, cefuroxime, cefdinir, cefpodoxime, cefprozil, or intramuscular ceftriaxone). 

Cefalexin is a first-generation cephalosporin and therefore an alternative preparation would be Zinnat tablets, which contains cefuroxime, a second-generation cephalosporin. A penicillin such as Augmentin, which contains co-amoxiclav, can be an appropriate alternative since it provides a very similar spectrum of activity. Klaricid contains clarithromycin, which is a macrolide. Utinor contains norfloxacin, which is a quinolone that is effective in uncomplicated urinary-tract infections. Rocephin contains ceftriaxone, which is a third-generation cephalosporin that is available for parenteral administration only. 

Cefuroxime is a second-generation cephalosporin with enhanced activity against Haemophilus influenzae, a Gram-negative organism. Side-effects include nausea, vomiting and headache. 

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. 

A microorganism with the required activity was found as Glaxo were already developing esterases to convert cephalosporin C into desacetyl cephalosporin C and some of these proved able to prodnce cefuroxime and to be cost effective on a process scale (Figure 4.9). 

The excellent biological activity of the cefuroxime, including a broad spectmm of effective antibacterial activities and good / -lactamase stability, has created a... 

Penicillins (bactericidal inhibit cell wall crosslinking) e.g., benzylpenicillin, phenoyxmethylpenicillin, ampicillin, amoxicillin, flu-cloxacillin, methicillin, piperacillin Cephalosporins (bactericidal inhibit cell wall crosslinking) e.g., cefaclor, cefalexin, cefradine, cefuroxime, cefazolin, cefotaxime, ceftriaxone, cefoxitin, cefsulodin, ceftazidime, ceftizoxime Monobactams (bactericidal, P-lactam-like activity) e.g., aztreonam... 

Cefaclor, cefuroxime axetil, cefprozil, and loracarbef can be given orally. The usual dosage for adults is 10-15 mg/kg/d in two to four divided doses children should be given 20-40 mg/kg/d up to a maximum of 1 g/d. Except for cefuroxime axetil, these drugs are not predictably active against penicillin-resistant pneumococci and should be used cautiously, if at all, to treat suspected or proved pneumococcal infections. Cefaclor is more susceptible to 13-lactamase hydrolysis compared with the other agents, and its usefulness is correspondingly diminished. 

Cephalexin Oral, first-generation drug, used for treating skin and soft tissue infections and urinary tract infections Cefuroxime Oral and intravenous, second generation drug, improved activity versus Pneumococcus and Haemophilus influenzae... 

Cefuroxime is also a second-generation cephalosporin resistant to some -lactamases. It is used in veterinary medicine in intramammary treatments. Cefuroxime axetil is also a prodrug active by the oral route. It is absorbed from the gastrointestinal tract and its absorption is enhanced if the compound is given after... 

O NH2 cefuroxime- 0 X T o o o AA 2nd generation, orally active hydrolysed by esterases to liberate cefuroxime... 

For premedication aspirin 300 mg twice a day 48 hours prior to the procedure and a loading dose of clopidogrel 300 mg (or ticlopidine 250 mg) is recommended. Endocarditis prophylaxis with a first generation cephalosporin (e.g., cefuroxime, 1, 5 g, i.v.) should be administered before and after intervention. After transseptal puncture, 10,000 units of heparin are administered. An activated clotting time of 200-300 seconds is desirable. 

A very comprehensive multicenter, randomized, double-blind study of two parallel treatment arms (the MOSAIC study MOxifloxacin compared to Standard therapy in Acute Infectious exacerbations of Chronic infections) demonstrated the powerful clinical activity of moxifloxacin for the treatment of AECB. Five-day treatment with moxifloxacin (400 mg, once daily for 5 days) was found to produce clinical cure rates that were superior to those achieved with 7-day treatment with a standard antibiotic (amoxicillin 500 mg three times daily for 7 days clarithromycin 500 mg twice daily for 7 days cefuroxime 250 mg twice daily for 7 days) [184]. 

The compound (which had a dihydrothiazine ring fused to the P-lactam core) showed resistance to P-lactamases and was less toxic than benzylpenicillin. The discovery that the basic building block, namely 7-aminocephalosporanic acid (7-ACA), could be synthesised, led to the preparation of numerous cephalosporin derivatives eg cephalothin, cephaloglycin (orally active), cefaclor and cefuroxime (Figure 7). 

Whereas many cephalosporins such as cefaclor, cefadroxil, cefonicid, ceforanide, ceftazidime, cefti-zoxime, cefuroxime, cephalexin, and cephradine are not metabolized, cefamandole naftate is rapidly hydrolyzed in plasma to cefamandole, which has greater antibacterial activity than the parent compound. Ceftriaxone is metabolized to a small extent to micro-biologically inactive metabolites in the intestines after biliary excretion. Cefuroxime axetil is rapidly hydrolyzed to cefuroxime, the microbiologically active form of the drug, by nonspecific esterases in the intestinal mucosa and blood following oral administration. The axetil moiety is further metabolized to acetaldehyde and acetic acid [93]. 

In cephalosporins susceptible to P-lactamases, opening of the [3-lactam ring occurs with concomitant loss of the substituent at R2 (except in cephalexin, where R2 represents H see Fig. 10.4). This is followed by fragmentation of the molecule. Provided that they are not inactivated by 3-lactamases, the cephalosporins generally have a broad spectrum of activity, although there may be a wide variation. Haemophilus influenzae, for example, is particularly susceptible to cefuroxime see also Table 10.2. 

Parenterally administered cephalosporins that are metabolically stable and that are resistant to many types of (3-lactamases include cefuroxime, cefamandole, cefotaxime and cefoxitin, which has a 7(3-methoxy group at R2. Injectable cephalosporins with anti-pseudomonal activity include ceftazidime, cefsulodin and cefoperazone. 

---