Cephalosporins toxicity

Aside from mild or severe allergic reaction, the most commonly experienced cephalosporin toxicities are mild and temporary nausea, vomiting, and diarrhea associated with disturbance of the normal flora. Rarely, a life-threatening pseudomembranous colitis diarrhea associated with the opportunistic and toxin-producing anaerobic pathogen, Clostridium difficile, can be experienced. Rare blood dyscrasias, which can even include aplastic anemia, also are seen. Certain structural types (details below) are associated with prolonged bleeding times and an antabuse-like acute alcohol intolerance. 

Other adverse reactions that may be seen with administration of the cephalosporins are headache, dizziness, nephrotoxicity (damage to the kidneys by a toxic substance), malaise, heartburn, and fever. Intramuscular (IM) administration often results in pain, tenderness, and inflammation at the injection site Intravenous (IV) administration has resulted in thrombophlebitis and phlebitis. 

Tune, B.M., Sibley, R.K. and Hsu, C.Y. (1988). The mitochondrial respiratory toxicity of cephalosporin antibiotics. An inhibitory effect on substrate uptake. J. Pharmacol. Exp. Ther. 245 1054-1059. 

Tune, B.M., Fravert, D. and Hsu, C.Y. (1989). Oxidative and mitochondrial toxic effects of cephalosporin antibiotics in the kidney A comparative study of cephaloridine and cephaloglycine. Biochem. Pharmacol. 38 795-802. 

Cephalosporins. These beta-lactam antibiotics share many features with the penicillins including mechanism, spectrum of action, distribution ans toxicity potential. At the present time, the cephalosporins are classified into three groups, designated as generations. 

Cephalosporins are the agents of choice in renal failure. They attain adequate urine concentrations despite severely impaired renal function and toxicity remains low with increased plasma levels. Quinolones are preferred over aminoglycosides due to aminoglycoside-related ototoxicity. 

Vancomycin and teicoplanin display excellent activity against staphylococci and streptococci, but because of the wide availability of equally effective and less toxic drugs, they are second-line drugs in the treatment of most infections. As antistaphylococcal agents they are less effective than 3-lactam cephalosporin antibiotics, such as nafciUin and cefazoUn. They have attained much wider use in recent years as a consequence of the emergence of methicUlin-resistant S. aureus (MRSA) infections, in particular the growing importance of Staphylococcus epidermidis infections associated with the use of intravascular catheters and in patients with peritonitis who are on continuous ambulatory peritoneal dialysis. 

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. 

Adverse reactions to cefuroxime have been generally mild and transient in nature. As with other cephalosporins there have been rare reports of erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis (exanthematic necrolysis) and hypersensitivity reactions including skin rashes, urticaria, pruritus, drug fever, serum sickness and very rarely anaphylaxis. 

The nucleus of the cephalosporins, 7-aminocephalosporanic acid (Figure 43-6), bears a close resemblance to 6-aminopenicillanic acid (Figure 43-1). The intrinsic antimicrobial activity of natural cephalosporins is low, but the attachment of various Ri and R2 groups has yielded hundreds of potent compounds of low toxicity (Figure 43-6). Cephalosporins can be classified into four major groups or generations, depending mainly on the spectrum of antimicrobial... 

The clinical effectiveness of the cephalosporins depends on a number of properties. The antibiotic must inhibit, or preferably kill, bacteria at acceptable concentrations of the drug (in vitro activity) it must be capable of achieving host serum and tissue levels greater than those required to inhibit the pathogenic organism and the selective toxicity profile must allow for safe administration to the host. 

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