Antibiotics cephalosporins, cephalexin

The P-lactam antibiotic cephalosporin is one of the most important drugs for the treatment of bacterial infections. Recently, several new compounds such as ce-fadroxil (2-161), cephalexin (2-162), cefixime (2-163), and cefzil (2-167) have been isolated, which contain an alkyl or alkenyl substituent instead of an acetoxymethyl group at C-3 (Scheme 2.37 and 2.38) [88]. 

Cephalexin (Keflex, Panixine DisperDose) [Antibiotic/ Cephalosporin-1st Generation] Uses Skin, bone, upper/lower resp tract, urinary tract Infxns Action lst-gen cephalosporin X- cell wall synth Dose Adults. 250-1000 mg PO qid Feds. 25—100 mg/kg/d PO - qid 4- in renal impair (on empty stomach) Caution [B, +] Contra Cephalosporin allergy Disp Caps, tabs, susp SE D, rash, eosinophilia, T LFTs Interactions T Nephrotox W/aminoglycosides, loop diuretics T effects W/probenecid EMS T Risk of adverse effects w/ loop diuretics monitor for signs of electrolyte disturbances and hypovolemia d/t D monitor pt for super Infxn OD May cause N/V/D, Szs, muscles spasms symptomatic and supportive... 

Penicillin G as well as approx. 4 kt a-1 of penicillin V are enzymatically hydrolyzed into the -lactam nucleus 6-aminopenicillanic acid (6-APA), which is the building block for the semisynthetic penicillin antibiotics ampicillin and amoxycillin [121] (see Fig. 8.23). Part of the penicillin G is converted into 7-aminodesa-cetoxycephalosporanic acid (7-ADCA, 3 kt a-1), which is the intermediate for the semisynthetic cephalosporins cephalexin and cefadroxil [122]. 7-ADCA has traditionally been produced from penicillin G via a chemical ring expansion but an all-bio process has recently been started up by DSM. 

The disadvantage of cephalosporin C is that it is not absorbed in the gastrointestinal tract, and it took nntil 1969 before the first oral cephalosporin, cephalexin 2 came to be used broadly in the clinic. However, the potential was sufficient to justify at least two decades of research and development by many pharmaceutical companies. Modifications at C-3 and C-7 led to a series of improved antibiotic compounds suitable for use in mammals, including domestic animals, companion animals, and humans, either administered as a solution by injection or as a solid using an oral formulation. More detailed accounts are available for the interested reader. ... 

The cephalosporins comprise another important class of broad-spectrum j8-lactam antibiotics. Cephalosporins were originally isolated from cultures of Cephalosporium acremonium. Cephalexin (Keflex) is a semisynthetic cephalosporin frequendy prescribed to treat ear and sldn infections caused by staphylococci or streptococci. 

Potential for Other Antibiotics The SLMs also have the potential for the removal and recovery of other antibiotics, including Cephalexin, Ampicillin, and Amoxicillin. Cephalexin is in the cephalosporin class of antibiotics, and it is one of the most prescribed antibiotics, approximately 3000 tons/year worldwide (Sheldon, 2004). The cephalosporin molecules contain acid and amine functional groups, which are amendable for complexation with extractants incorporated in liquid membranes. Studies on the... 

Cephalosporins first entered the marketplace in 1964, when cephalothin (27) and cephaloridine (51), which are both injectable, were launched. By the late 1970s, the injectable cephalosporins had become important therapeutic agents in the hospitals. Also in 1964 the first oral cephalosporin, cephaloglycin [3577-01 -3] C gH N OgS, was launched only to be displaced by the end of the year by cephalexin (12). For years cephalexin was the leading oral cephalosporin on the market. It has since been displaced by cefaclor (13). With the advent of the more -lactamase stable cephalosporins such as cefoxitin (23) and cefuroxime (35), and the more potent agents such as cefotaxime (36) and other third-generation compounds, cephalosporins now dominate the antibiotic market worldwide. 

Closely related to the penicillins are the cephalosporins, a group of /3-lactam antibiotics that contain an unsaturated six-membered, sulfur-containing ring. Cephalexin, marketed under the trade name Keflex, is an example. Cephalosporins generally have much greater antibacterial activity than penicillins, particularly against resistant strains of bacteria. 

Given that hydrolysis is a reversible reaction, the principle of microscopic reversibility implies that biocatalytic aminoacylation should also be applicable as a mild and efficient alternative method of introducing the side chain of both penicillin- and cephalosporin-based antibiotics. This is the case, with PGAs proving to be particularly effective biocatalysts towards the aminoacylation of both penicillin and cephalosporin nuclei with a variety of carboxyhc acids. Amoxicillin and cephalexin, two of the most important (3-lactam antibiotics, contain an (/ )-phenylglycine side chain which cannot be directly introduced as the amino acid due to its zwitterionic nature at the moderate pH values at... 

Baseline separation of the cephalosporin antibiotic cephradine, its main impurity cephalexin, and other related impurities was achieved by MEKC. The method was validated in compliance with the USP XXII analytical performance parameters and the results were comparable with a validated LC method, depicting CE to be a valuable alternative technique to LC in pharmaceutical quality control. In most cases, the amount of impurities relative to the main compound measured by MEKC is similar to that obtained by LC. However, some reports reveal that there are differences in number and amount of impurities between MEKC and LC analysis. MEKC permitted the determination of seven known and three unknown impurities in cefotaxime and the results were in good agreement with those of LC. ° MEKC yielded a higher amount of the cefotaxime dimer but a lower amount of an unidentified impurity with respect to LC. The differences may be due to the easier formation of the dimer in the aqueous sample solvent used in MEKC compared to the hydroorganic... 

Antibiotics based on a related ring system, termed the cephems (figure 23.2), are highly useful. Here the five-membered ring has been expanded to six and the double bond of the penems retained. These are the cephalosporins and include such important antibiotics as cephalothin (Keflin), cefazolin (Ancef), cephalexin (Keflex), cefamandole (Cefam), cefuroxime (Zinacef), cefeclor (Ceclor) and cefoxitin (Mefoxin). 

Since amides are often used as acyl donors in the enantioselective acylation of amines, a combination of a NHase and an amidase could, in principle, be used for the direct acylation of an amine by the nitrile precursor of the amide. An example of such a one-pot reaction is shown in Scheme 6.20. The (R)-enantiomer of phenylglycine nitrile undergoes NHase-catalyzed conversion to the corresponding (R)-amide and the latter reacts in situ with 7-aminodeacetoxycephalosporanic acid, in the presence of penidlhn amidase, to afford the cephalosporin antibiotic, cephalexin [39]. 

Penicillins, such as penicillin G and cephalosporins, such as cephalexin, as well as most other antibiotics, are produced by microorganisms that can be mass-produced in large vats. The antibiotics are then harvested and purified. 

The specifically 13C-enriched compounds were useful for the signal identification of the 13C NMR spectrum of this microbial product. Spectral comparison of cephalosporin C with a-aminoadipic acid-N-ethylamide, cephalexin, 3-methyl-7 (2-phenoxyacetamido)-3-cepham and 7-amino cephalosporanic acid led to the total signal identification of this antibiotic. The shifts are listed in Table 5.46. 

It has also been reported that patients with allergic-like events after penicillin treatment have had a markedly risk of events after subsequent cephalosporin antibiotics. Cross-reactivity is not an adequate explanation for this increased risk and the data obtained indicate that cephalosporins can be considered for patients with penicillin allergy <2006MI354.ell>. Comparisons of parenteral broad-spectrum cephalosporins have been tested against bacteria isolated from pediatric patients. The results have indicated that cefepime has been the most broad-spectrum cephalosporin analyzed and it is a very potent alternative for the treatment of contemporary pediatric infections in North America <2007MI109>. The historical safety of the most commonly used oral cephalosporins has been reviewed <2007MIS67>. The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil and cephalexin has also been reviewed <2007MIS5>. 

However, cortical concentration does not appear to be the sole determinant of toxicity for other cephalosporin antibiotics, since several cephalosporins reach high cortical concentrations without producing nephrotoxicity. For example, both cepha-loglycin and cephaloridine produce nephrotoxicity whereas cephalexin is not nephrotoxic. Cortical concentrations of cephaloridine, cephaloglycin, and cephalexin are approximately equal initially (0-2 hr) following treatment with these antibiotics. While cortical cephaloridine concentration does not decline, cortical concentrations of both cephaloglycin and cephalexin decline in a similar fashion over 3 hr. Thus,... 

Bacterial dacryoadenitis should be treated with specific antibiotics after culture and sensitivity testing. Until results are obtained, many practitioners recommend an oral first-generation cephalosporin, such as cephalexin (Keflex, 500 mg four times a day for adults) or amoxicillin (250 to 500 mg three times a day for adults).This regimen should be followed for 7 days. Gonorrheal dacryoadenitis is treated with penicillin administered intramuscularly or with tetracycline taken orally. 

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