DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 53–3
Cephalosporin Generations
EXAMPLES
First Generation
Cefazolin (ANCEF, ZOLICEF, others)
Cephalexin monohydrate (KEFTAB)
Cefadroxil (DURACEF)
Cephradine (VELOSEF)
Second Generation
Cefuroxime (ZINACEF)
Cefuroxime axetil (CEFTIN)
Cefprozil (CEFZIL)
Cefmetazole (ZEFAZONE)
Loracarbef (LORABID)
Third Generation
Cefotaxime (CLAFORAN)
Ceftriaxone (ROCEPHIN)
Cefdinir (OMNICEF)
Cefditoren pivoxil (SPECTRACEF)
Ceftibuten (CEDAX)
Cefpodoxime proxetil (VANTIN)
Ceftizoxime (CEFIZOX)
Cefoperazone (CEFOBID)
Ceftazidime (FORTAZ, others)
Fourth Generation
Cefepime (MAXIPINE)
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USEFUL SPECTRUM a
Streptococci b ; Staphylococcus aureus. c
Escherichia coli, Klebsiella, Proteus, Haemophilus influenzae,
Moraxella catarrhalis. Not as active against gram-positive organisms
as first-generation agents.
Inferior activity against S. aureus compared to cefuroxime but with
added activity against Bacteroides fragilis and other Bacteroides spp.
Enterobacteriaceae d ; Pseudomonas aeruginosa e ; Serratia; Neisseria
gonorrhoeae; activity for S. aureus, Streptococcus pneumoniae,
and Streptococcus pyogenes f comparable to first-generation agents.
Activity against Bacteroides spp. inferior to that of cefoxitin and
cefotetan.
Active against Pseudomonas
Comparable to third generation but more resistant to some β-lactamases.
a
All cephalosporins lack activity against enterococci, Listeria monocytogenes, Legionella spp., methicillin-resistant S. aureus, Xanthomonas
maltophilia, and Acinetobacter species. b Except for penicillin-resistant strains. c Except for methicillin-resistant strains. d Resistance to
cephalosporins may be induced rapidly during therapy by de-repression of bacterial chromosomal β-lactamases, which destroy the
cephalosporins. e Ceftazidime only. f Ceftazidime lacks significant gram-positive activity. Cefotaxime is most active in class against S.
aureus and S. pyogenes.
Many gram-positive microorganisms release relatively large amounts
of β-lactamase into the surrounding medium. Although gram-negative
bacteria seem to produce less β-lactamase, the location of their
enzyme in the periplasmic space may make it more effective in
destroying cephalosporins because they diffuse to their targets on the
inner membrane, as is the case for the penicillins. The cephalosporins
have variable susceptibility to β-lactamase. For example, of the firstgeneration
agents, cefazolin is more susceptible to hydrolysis by β-
lactamase from S. aureus than is cephalothin (no longer marketed).
Cefoxitin, cefuroxime, and the third-generation cephalosporins are
more resistant to hydrolysis by the β-lactamases produced by gramnegative
bacteria than first-generation cephalosporins. Third-generation
cephalosporins are susceptible to hydrolysis by inducible,
chromosomally encoded (type I) β-lactamases. Induction of type I β-
lactamases by treatment of infections owing to aerobic gram-negative
bacilli (especially Enterobacter spp., Citrobacter freundii, Morganella,
Serratia, Providencia, and P. aeruginosa) with second- or thirdgeneration
cephalosporins and/or imipenem may result in resistance to
all third-generation cephalosporins. The fourth-generation cephalosporins,
such as cefepime, are poor inducers of type I β-lactamases and are less
susceptible to hydrolysis by type I β-lactamases than are the thirdgeneration
agents. They are, however, susceptible to degradation by
KPC and metallo-β-lactamases (Jacoby and Munoz-Price, 2005; Jones
et al., 2008; Walsh, 2008).
General Features of the Cephalosporins. Cephalexin,
cephradine, cefaclor, cefadroxil, loracarbef, cefprozil,
cefpodoxime proxetil, ceftibuten, and cefuroxime axetil
are absorbed readily after oral administration. Cefdinir
and cefditoren are also effective orally. The other
cephalosporins can be administered intramuscularly or
intravenously. Cephradine and loracarbef have been
discontinued in the U.S.
Cephalosporins are excreted primarily by the kidney;
thus the dosage should be altered in patients with
renal insufficiency. Probenecid slows the tubular secretion
of most cephalosporins. Exceptions are cefpiramide
and cefoperazone, which are excreted predominantly in