Third-generation agents cephalosporins

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. 

Most cephalosporins do not penetrate into the CSF third-generation agents achieve therapeutic levels in CSF r>... 

Clearance of first-generation cephalosporins after intravitreal injection suggests a posterior clearance route (23). Newer agents may be removed by the anterior route or by the combined posterior and anterior route (30). In phakic eyes, the half-life of cefazolin in the monkey and the rabbit is 6.5 7 hours (22,45). The half-life is decreased by inflammation, presumably by interference with active transport across posterior structures. In studies of third-generation agents (ceftizoxime and ceftriaxone), there was increased drug half-lives in infected rabbit eyes as compared to controls (30). Ceftazadime has a half-life of 13.8 20 hours in the rabbit, but the half-life is dramatically lowered by removal of the lens and vitreous (46). 

Second-generation cephalosporins generally have been displaced by third-generation agents. The oral second-generation cephalosporins can be used to treat respiratory tract infections, although they are inferior to amoxiciUin for treatment of peniciUin-resistant S. pneumoniae pneumonia and otitis media. Cefoxitin and cefotetan both are effective in situations where facultative gramnegative bacteria and anaerobes are involved e.g., intra-abdominal infections, pelvic inflammatory disease, and diabetic foot infection). 

The cephalosporins are classified as first-, second-or third-generation agents. They differ in terms of antibacterial spectmm, stability to bacterial P-lactamases and... 

The third-generation agents display a broader spectmm of antibacterial activity compared to the first- and second-generation cephalosporins. Although these agents display... 

Drugs of choice are not yet identified. Y. enterocolitica is generally susceptible to fluoroquinolones, alone or in combination with third-generation cephalosporins or aminoglycosides. Alternative agents include chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole. 

Cephalexin, cefaclor, cefprozil, cefadroxil, ceftibuten, and loracarbef are well absorbed from the Gl tract. Cephalosporins are widely distributed to most tissues and fluids. First and second generation agents do not readily enter cerebrospinal fluid (CSF), except cefuroxime, even when meninges are inflamed. Third generation compounds readily diffuse into the CSF of patients with inflamed meninges. However, CSF levels of cefoperazone are relatively low. Most cephalosporins and metabolites are primarily excreted renally. 

With the advent of potent broad-spectrum antibiotics, such as the quinolones and third-generation cephalosporins, the indications for the use of the polymyxins, with their serious potential for toxicity, are few. Their only justifiable use may be as topical agents. 

Cephalosporins are semisynthetic antibiotics obtained from the fungus Cephalo-sporium. These bactericidal agents act in a similar way to that of penicillins. There are different types of cephalosporins available first-generation (cefazolin, cefadroxil) second-generation (cefuroxime, cefaclor) third-generation (cefotaxime, cefoperazone) and fourth-generation (cefpirome). 

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