Cephalosporins classification

A beta-lactam-like antibiotic. These drugs are included in the cephalosporin classification but are not true cephalosporins. They are, however, similar in structure and mechanism. 

It should be noted that the classification iato generations is not chronological, and so some second-generation compounds came to the market relatively recendy, after the third-generation was firmly estabUshed. Within each class there is also a further classification as to whether the compounds are administered orally or parenteraHy. A contemporary variation of the generation classification has been proposed, but has not found widespread use (85). Another proposal groups cephalosporins according to clinical indication or appHcation (86). 

The large number and diversity of available /3-lactams, mainly penicillins and cephalosporins, necessitate their classification. Penicillins can be classified primarily according to chemical structure. Table 5.2 shows that there is good correspondence between chemical structure and properties. The categorization of cephalosporins into chemically similar groups is not useful because their antimicrobial spectrum is not closely correlated with chemical structure, and classification into generations is based on their spectrum of microbial activity (Table 5.3). 

Figure 1.6 Number of antibiotic prescriptions per 1000 inhabitants per antibiotic anatomical therapeutic chemical (ATC) classification in 13 European countries in 1997. In parentheses are the ATCs used by the WHO. Tet = tetracyclines, Pen = penicillin, Ex-Pen = extended-spectrum penicillins, B-Lac = (3-lactamase-sensitive penicillins. Cep = cephalosporins, TMP = trimethoprim (alone or in combination), Mac + Lin = macrolides and lincosamides, Mac = macrolides, Lin = lincosamides. Ami = aminoglycosides, and Qui = quinolone. The 13 countries are SP = Spain, GR = Greece, BG = Belgium, PR = Prance, PL = Portugal, IT = Italy, PI = Pinland, UK = United Kingdom, DE = Denmark, AU = Austria, GE = Germany, SW = Switzerland, and NL = Netherlands. (Based on data from Molstad et al., 2002.)...

The following section has two main objectives first, to summarize the classification of cephalosporins in terms of their spectrum of activity and second, to provide an overview of the new cephalosporin antibiotics discovered in the last decade. 

Classification and uses. The cephalosporins are conventionally categorised by generations having broadly similar antibacterial and pharmacokinetic properties newer agents have rendered this classification less precise but it retains sufficient usefulness to be presented in Table 12.1. 

The cephalosporins represent a family of beta-lactam antibiotics originally derived from the naturally occurring cephalosporin C. Isolation of the cephalosporin C nucleus, 7-aminocephalosporanic acid, made it possible to introduce new groups into this molecule to obtain the current variety of compounds (1). Cephalosporins vary widely in their antibacterial properties, beta-lactamase stability, and pharmacokinetic behavior, but there is as yet no unequivocal classification (2). For reasons more practical than pharmacological, cephalosporins are often classified into first-, second-, third- and fourth-generation compounds, as shown in Table 1. 

Ceftiofur is marketed as a "new" generation cephalosporin as it does not clearly fall into the previous classification scheme. It is currently approved for the treatment of streptococcal infections in horses. It has broader Gram-positive spectrum of activity than the third-generation cephalosporins and has activity against anaerobes. Ceftiofur has no activity against Pseudomonas spp. and does not penetrate into the CNS. It is metabolized very rapidly in vivo to its active metabolite desfuroylceftiofur. Desfuroylceftiofur is very highly protein bound because of a sulfhydryl... 

Lactamases may be chromosomal or plasmid-borne, inducible or constitutive, and for this reason their terminology can be confusing. A number of classification systems have been proposed, including classes A-D based on peptide sequence. Classes A, C and D have a serine at the active site, whereas class B enzymes have four zinc atoms at their active site and these are also called metallo-(3-lactamases. Class A enzymes are highly active against ben-zylpenicillin, class B (3-lactamases are effective against penicillins and cephalosporins. Class C en-... 

Table 6-4 lists cephalosporins available in the United States in a more or less chronological order of their introduction, usually termed as generations. This has become a useful classification since newer P-lactams were introduced primarily to overcome the shortcomings of the earlier compounds. Thus later agents tended to have broader antibacterial spectra, increased resistance to P-lactamase inactivation, less toxicity, or some combination of these features. 

For this review another classification is used. As the majority of peptide antibiotics are of unknown structure and cannot therefore be classified chemically, they are grouped according to the organism which produces them. At the beginning of every section, the peptide antibiotics are listed in a table which gives the known characteristics and the literature. Only the clinically useful members are described in detail. Furthermore, only those peptide antibiotics which consist mainly of amino acids in peptide linkages are fully considered. The important actinomycins , penicillins and cephalosporins, which have been reviewed several times in recent years, are not included here. Amino acids and amino acid residue sequences are denoted in accordance with the suggestions of the committee on nomenclature which reported at the Fifth European Peptide Symposium . When necessaiy the direction of the —CO NH— bond is indicated by an arrow (— )., ... 

A. Classification The cephalosporins are derivatives of 7-aminocephalosporanic acid and contain the beta-lactam ring structure. Many members of this group are in clinical use. They vary in their antibacterial activity and are designated first-, second-, third-, or fourth-generation drags according to the order of their introduction into clinical use. 

Most cephalosporins have generic names beginning with cef- or ceph-. This is convenient for classification, but it makes discriminating between individual members a true memory test. The cephalosporins are... 

Penicillins and cephalosporins are prototypes for allergic reactions of type I by the classification of Coombs and Gell (1963), based on the pathogenetic mechanisms. They are mostly IgE mediated. But type III and type IV reactions also occur. 

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