Cefotaxime is highly resistant to many ¡ -lactamases and has good activity against many bacteria; activity against B. fragilis is poor compared with clindamycin or metronidazole. Cefotaxime should be administered every 4-8 hours for serious infections. The drug is metabolized in vivo to desacetylcefotaxime, which is less active against most microorganisms than the parent compound but acts synergistically with the parent compound against certain microbes. Cefotaxime has been used effectively for meningitis caused by H. influenzae, penicillin-sensitive S. pneumoniae, and N. meningitides.
Ceftizoxime has a spectrum of activity that is very similar to that of cefotaxime, except that it is less active against S. pneumoniae and more active against B. fragilis. The drug can be administered every 8—12 hours for serious infections. Ceftizoxime is not metabolized, and 90% is recovered in urine.
Ceftriaxone has activity very similar to that of ceftizoxime and cefotaxime but a t/2 of ~8 hours. Administration of the drug once or twice daily has been effective for patients with meningitis, and dosage once a day is effective for other infections. About half the drug can be recovered in the urine; the remainder is eliminated by biliary secretion. A single dose of ceftriaxone (125-250 mg) is effective in the treatment of urethral, cervical, rectal, or pharyngeal gonorrhea, including peni-cillinase-producing microorganisms.
Cefpodoxime proxetil is an orally administered third-generation agent that is very similar in activity to the fourth-generation agent cefepime (see below) except that it is not more active against Enterobacter or Pseudomonas spp.
Cefditoren pivoxil is a prodrug that is hydrolyzed by esterases during absorption to the active drug, cefditoren. Cefditoren is eliminated unchanged in the urine. The drug is active against methicillin-susceptible strains of S. aureus, penicillin-susceptible strains of S. pneumoniae, S. pyogenes, H. influenzae, H. parainfluenzae, and Moraxella catarrhali. Cefditorenpivoxil is only indicated for the treatment of mild-to-moderate pharyngitis, tonsillitis, uncomplicated skin and skin structure infections, and acute exacerbations of chronic bronchitis.
Ceftibuten is an orally effective drug that is less active against gram-positive and gramnegative organisms than cefixime, with activity limited to S. pneumonia and S. pyogenes, H. influen-zae, and M. catarrhalis. Ceftibuten is only indicated for acute bacterial exacerbations of chronic bronchitis, acute bacterial otitis media, pharyngitis, and tonsillitis.
Cefdinir is effective orally; it is eliminated primarily unchanged in the urine. Cefdinir has a spectrum of activity similar to cefixime. It is inactive against Pseudomonas and Enterobacter spp.
Third-Generation Cephalosporins with Good Activity Against Pseudomonas
Ceftazidime is one-quarter to one-half as active against gram-positive microorganisms as cefotaxime. Its activity against the Enterobacteriaceae is very similar; its major distinguishing feature is excellent activity against Pseudomonas and other gram-negative bacteria. Ceftazidime has poor activity against B. fragilis. The drug is not metabolized.
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