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Journal Article
Review
In vitro activity, pharmacokinetics, clinical efficacy, safety and pharmacoeconomics of ceftriaxone compared with third and fourth generation cephalosporins: review.
Journal of Chemotherapy 2005 Februrary
Due to their wide spectrum of activity, good pharmacokinetics, established clinical efficacy and high tolerability, cephalosporins are among the most widely used antibiotics worldwide. The third and fourth generation cephalosporins are predominantly parenteral agents, administered two or three times daily, used in the treatment of a wide range of moderate to severe infections. Ceftriaxone, a third generation cephalosporin, is unique in exhibiting an unusually long elimination half-life that allows for once-daily administration. Among third generation cephalosporins, ceftazidime and cefoperazone are unusual among cephalosporins in possessing activity, albeit moderate, against Pseudomonas aeruginosa. However, both of these agents also exhibit marked loss of activity against Gram-negative organisms producing high levels of Class A or C beta-lactamases. Sulperazone, a 1:1 combination of cefoperazone and the beta-lactamase inhibitor sulbactam, is more resistant to attack by Class A beta-lactamases but remains vulnerable to isolates producing Class C beta-lactamases. Ceftriaxone exhibits the widest antibacterial spectrum of third generation cephalosporins and this is reflected in clinical responses. Cefoperazone and sulperazone exhibit the poorest clinical responses. Although the fourth generation cephalosporins cefpirome and cefepime exhibit enhanced stability to bacterial beta-lactamases and marginally enhanced in vitro antibacterial activity over ceftriaxone, there is no clinical advantage in terms of clinical or bacteriological success. The cephalosporins are well tolerated, with few and generally transient adverse effects; the major exception being haematological abnormalities including blood coagulation disorders associated with cefoperazone. Several pharmacoeconomic studies indicate that the once-daily dosing regimen required for ceftriaxone is the major factor responsible for its cost-effectiveness over third and fourth generation cephalosporins.
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