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  • Title: Third-generation cephalosporins: a critical evaluation.
    Author: Barriere SL, Flaherty JF.
    Journal: Clin Pharm; 1984; 3(4):351-73. PubMed ID: 6432420.
    Abstract:
    Six third-generation cephalosporins--cefotaxime, moxalactam, cefoperazone, ceftizoxime, ceftriaxone, and cefmenoxime--are reviewed; covered are chemistry and structure-activity relationships, mechanism of action, spectra of activity, pharmacokinetics, clinical utility, adverse effects, and cost effectiveness. The third-generation cephalosporins have a similar mechanism of action to that of other beta-lactam antibiotics. None of the agents is particularly active against certain gram-positive bacteria, including methicillin-resistant Staphylococcus aureus; the drugs are effective against gonococci, Haemophilus influenzae, and Neisseria meningitidis. Several common gram-negative pathogens are susceptible to the third-generation cephalosporins, including Escherichia coli, Klebsiella, Citrobacter diversus, Proteus, and Morganella. About 50% of Pseudomonas aeruginosa isolates are susceptible. Only moxalactam has good activity against Bacteriodes fragilis. The pharmacokinetic profiles of the six agents reveal some important differences. The half-life of ceftriaxone allows once-daily dosing in many patients; the half-lives of ceftizoxime and cefoperazone permit dosing every 8-12 hours. Cefoperazone and ceftriaxone are highly protein bound, but the clinical relevance of this is unknown. Generally, the agents penetrate most body tissues and fluids well. Moxalactam and cefotaxime and possibly ceftriaxone effectively penetrate into the cerebrospinal fluid well. The third-generation cephalosporins have become the accepted drugs of choice for the treatment of adult gram-negative bacillary meningitis; as more experience is gained, they are likely to become the drugs of first choice for neonatal (with ampicillin) and childhood (except for moxalactam) meningitis. Serious infections of Enterobacteriaceae can be treated with these agents, thereby avoiding use of the aminoglycosides. Moxalactam is comparable with combination therapy in treating intra-abdominal infections. Adverse effects associated with use of the third-generation cephalosporins are generally similar to those that occur with other beta-lactam antibiotics with the exception of coagulopathies and the disulfiram reaction seen with moxalactam and cefoperazone. Despite the relatively high cost of the third-generation cephalosporins, they are often cost effective because of their reduced dosing frequencies, broad spectra of activity, and effectiveness in serious infections for which more toxic antibiotics have been required in the past.
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