Cephalosporins clinical reactions

The cephalosporins generally cause few side effects (80,132,219—221). Thrombophlebitis occurs as a result of intravenous administration of all cephalosporins. Hypersensitivity reactions related to the cephalosporins are the most common side effects observed, but these are less common than found with the penicillins. Clinically only about 5—10% of patients with allergic reactions to the penicillins manifest the same reactions to the cephalosporins, and data would contradict any tme cross-reactivity to cephalosporins in patients who have previously reacted to penicillin (80,132,219). 

Several authors have demonstrated the occurrence of hemagglutinating IgM and/ or IgG antibodies in patients treated with cephalothin (Abraham et al. 1968a,b Spath et al. 1971), without any evidence that such antibodies would cause harmful clinical reactions. In this, the situation resembles that with penicillin, with the exception that some cephalosporins obviously bind serum proteins to erythrocytes, a phenomenon whose immunopathological consequences are not yet entirely clear. 

The true incidence of allergic sensitization due to cephalosporins alone is difficult to assess, since in most patients treated with cephalosporins, the immune status for penicillin sensitivity before treatment is not objectively known and assessed. The general clinical impression is that in patients sensitized to benzyl-penicillin, overt allergic clinical reactions do not occur in more than 10%-20% of those subsequently treated with cephalosporins. The rate of adverse reactions may, however, be higher than suspected. In healthy volunteers given cephalothin and ce-phapirin intravenously, an unexpectedly high rate of reactions was experienced, and five patients developed skin hypersensitivity detected by skin test with PPL. 

Allergic responses to drugs are mediated by the release of histamine or histamine-like substances, and they commonly present as skin rashes, particularly urticaria. More serious hypersensitivity responses include bronchospasm or the acute, explosive anaphylactic reaction with cyanosis and cardiovascular collapse. A delayed reaction known as serum sickness, although more often associated with such drugs as the penicillins and cephalosporins rather than with serum, manifests clinically 7 to 10 days after receiving the drug or serum as fever, malaise, joint pains, and urticarial skin rashes. 

Grotsch H, Hajdu P. Interference by the new antibiotic cefpirome and other cephalosporins in clinical laboratory tests, with special regard to the Jaffe reaction. J Clin Chem Clin Biochem 1987 25(l) 49-52. 

A serum sickness-like reaction clinically similar to classical serum sickness can result from the administration of a number of non-protein drugs, such as tetracyclines, penicillins, cephalosporins (50). Minocycline has been reported to cause serum sickness (29,51). 

E213 Letellier, G. and Desjarlais, F. (1985). Analytical interference of drugs in clinical chemistry II. The interference of three cephalosporins with the determination of serum creatinine concentration by the Jaffe reaction. Clin. Biochem. 18, 352-356. 

Although cephalosporin C is divisable into a-aminoadipic acid, cysteine, and valine, the actual mechanism whereby Cephalosporium sp. incorporates the three amino acids into cephalosporin C has not been established, Arnstein and Morris isolated 8 (a-aminoadipyl) cysteinyl valine from mycelia of Penicillium chrysogenum and suggested that the tripeptide is a precursor in all penicillin biosynthesis.. This same tripeptide also appears to be found in the intracellular pool of Cephalosporium sp.- The final postulated step in the biosynthesis of penicillin is an acyl transfer reaction, or the production of 6-aminopeni-cillanic acid if precursor is not added. Cephalosporium sp. apparently do not produce sidechain amidases or acyl transferases, and no 7-ACA has been reported found in the fermentation. Thus, to obtain clinically useful antibiotics, chemical manipulation of cephalosporin C is necessary. Synthesis of many 7-acyl derivatives was possible once a practical cleavage reaction made available large amounts of 7-ACA from cephalosporin C. of these derivatives, sodium cephalothin was the first... 

Finally, there are a mixed bag of oxidases, catalysing ethylene formation in plants and many other diverse reactions, illustrated in Figure 13.20, by isopenicillin N-synthase, IPNS, which catalyses the cyclisation of the heterocyclic P-lactam ring. The importance of penicillin- and cephalosporin-related antibiotics in clinical medicine cannot be underestimated and has stimulated the study of their biosynthetic pathways. A key step in the biosynthesis of these antibiotics involves oxidative ring closure reactions of S-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to form isopenicillin N, the precursor of penicillins and cephalosporins, catalysed by IPNS (Figure 13.20). The overall reaction utilizes the full oxidative potential of O2, reducing it to two molecules of H2O. As discussed earlier, these enzymes are technically oxidases and the four electrons required for dioxygen reduction come from the substrate. 

C-7 Side-Chain Cleavage. 7-ACA (1), the key intermediate for the synthesis of a large number of the clinical cephalosporins, cannot be made by fermentation, nor can it be readily obtained by enzymatic removal (187) of the aminoadipic acid side chain from cephalosporin C. Because substantial quantities of 7-ACA are used, an efficient method for the chemical cleavage of the acyl side chain of cephalosporin C was sought. The first efficient method involved diazotization using nitrosyl chloride, followed by hydrolysis or alcoholysis, and gave 7-ACA in 50% yield (22,23,87,188). The reaction proceeds via the formation of the cyclic imino ether (57) which is easily hydrolyzed under very mild conditions. 

Together with the penicillins, the cephalosporin p-lactam antibacterials are the most widely used antibiotics for the treatment of common infections. The origin of cephalosporin antibiotics dates back to 1948 with the demonstration of antimicrobial action in a fungal extract from what was then called Cephalosporium acremonium. The Cephalosporium genus is now known as Acremonium. The cephalosporins used in medicine today are semisynthetic derivatives of the natural antibiotic cephalosporin C. Soon after cephalosporins were introduced into clinical use, adverse reactions including apparent hypersensitivity reactions and obvious anaphylactic responses began to appear, and although their similar structural features to the penicillins... 

Adverse reactions to the penicillin and cephalosporin antibiotics, two of the clinically most important families of antimicrobial drugs but also two of the most allergenic, are examined in detail in Chap. 5 and will not be discussed further here. The opioid group of drugs are responsible for around 2 % of reactions during the perioperative period. These histamine-releasing, clinically important analgesics are dealt with separately in Chap. 8. 

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