Idea Transcript
Journal of Antimicrobial Chemotherapy (1982) 10, Suppl. C, 135-140
Adverse effects of third-generation cephalosporins Richard Platt
Review of the adverse experiences of patients whose records were submitted to the U.S. Food and Drug Administration reveals that the third-generation agents, cefoperazone, cefotaxime, ceftizoxime, and moxalactam share a low incidence of the adverse effects which have also been observed for thefirst-generationcephalosporins. These include pain and phlebitis at injection sites, immediate and delayed hypersensitivity reactions, various haematological disorders, nephrotoxicity, hepatotoxicity, gastrointestinal disturbances, and fever. The rates at which these were observed ranged from < 1-12% and did not vary significantly among the thirdgeneration agents. Additional adverse effects which have been observed more often among thirdgeneration cephalosporins than first-generation agents are: suppression of endogenous gut flora leading to reduction in vitamin K. synthesis and occasionally causing clinically significant bleeding, pseudomembranous colitis, and inhibition of acetaldehyde dehydrogenase, causing acute ethanol intolerance. The latter appears to be restricted to compounds which contain a methyltetrazolethiol group. The overall clinical experience to date indicates that these agents will enjoy low toxicity similar to that observed for the first-generation cephalosporins. General considerations
The evaluation of adverse effects of antibiotics is hampered by a number of theoretical as well as practical obstacles. Many of these problems are common to all therapies used in serious illnesses. The major caveats which follow must be kept in mind when reviewing data about adverse reactions attributed to use of a drug. The illness which is the reason for therapy may cause problems that mimic adverse drug effects. These problems may be obvious such as the occurrence of seizures in patients with meningitis, or subtle such as chronic low grade coagulopathy caused by endotoxin. Conversely, some aspect of the illness under study may obscure genuine adverse effects. Thus the recognition of isoniazid-induced hepatitis was long delayed by the presumption that liver function test abnormalities were attributable to acknowledged or covert alcohol abuse by the target population. Both of these problems are examples of confounding by indication, that is, the association (either positive or negative) of the adverse effect with the disease itself independent of the effects association with the therapy. Reprint requests to: 180 Longwood Avenue, Boston, Massachusetts 02115. 135 0305-7453/82/10C135 + 06 $02.00/0 © 1982 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at Pennsylvania State University on May 9, 2016
Charming Laboratory, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
136
R. Platt
Table I. Cephalosporin adverse effects reported in U.S. pre-licensing clinical evaluation Cephalosporin classes Second Cefamandole 1278*
Third
Cefoxitin Cefoperazone Cefotaxime Ceftizoxime Moxalactam 1615 2000 1221 1559 3558
Gastrointestinal symptoms (nausea, vomiting,
diarrhoea) Pain at injection site/phlebitis Rash Eosinophilia Renal function abnormalities Liver function abnormalities * Patients reported, t Percentage.