Safety of parenteral third-generation cephalosporins

Abstract

Knowledge of side effects associated with different cephalosporins may be of help to prescribers. There are several side effects that are common to all cephalosporins, but overall, cefotaxime and ceftizoxime cause the fewest adverse reactions. Bleeding is probably the most common serious side effect of cephalosporins. Moxalactam causes coagulopathy and bleeding more often than do other cephalosporins, probably because it is carboxylated and has a methylthiotetrazole side chain. Cefoperazone also has a methylthiotetrazole side chain and may cause bleeding, particularly when used in doses greater than 4 g per day. Ceftriaxone has a similar side chain and there is some evidence that it can induce a coagulopathy. Coagulation tests should be monitored when any of the third-generation cephalosporins are given to patients with a high risk of bleeding. Disulfiram-like reactions are also related to the side chains associated with coagulation defects and have been reported when patients receiving cefoperazone, moxalactam, or ceftriaxone have ingested alcohol. Seizures have been reported with ceftazidime, but are uncommon. Hematologic reactions are rare with all third-generation cephalosporins. Benign diarrhea and Clostridium difficile colitis probably occur most often with moxalactam, cefoperazone, ceftazidime, and ceftriaxone, but there are few good data on this issue. Ceftriaxone has the unique ability to cause sludge (also referred to as pseudolithiasis) to form in the gallbladder, particularly in children. This may be associated with nausea, anorexia, epigastric distress, and colic, and is usually detected using ultrasonography. The sludge dissolves and symptoms subside after therapy is discontinued. None of the third-generation cephalosporins is clearly significantly nephrotoxic, even when combined with aminoglycosides. Most of the third-generation cephalosporins have surprisingly few serious side effects, which make them attractive for use in the treatment of a wide variety of serious infections.