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

Table 53–1
Chemical Structures and Major Properties of Various Penicillins (Continued)
MAJOR PROPERTIES
NONPROPRIETARY Absorption after Oral Resistance to
R NAME Administration Penicillinase
Carbenicillin Poor (not given orally)
(R 1
= H)
Carbenicillin Good No
indanyl
(R 1
= 5-indanol)
Ticarcillin Poor (not given orally) No
Useful Antimicrobial
Spectrum
Less active than ampicillin against Streptococcus species, Enterococcus
faecalis, Klebsiella, and Listeria monocytogenes. Activity against
Pseudomonas aeruginosa is inferior to that of mezlocillin and piperacillin
Mezlocillin Poor (not given orally) No
Piperacillin Poor (not given orally) No
Extends spectrum of ampicillin to include Psuedomonas aeruginosa, d
Enterobacteriaceae, b Bacteroides species b
a
Many strains are resistant due to altered penicillin-binding proteins. b Many strains are resistant due to production of β-lactamases. c There are other
congeners of ampicillin; see the text. d Some strains are resistant due to decreased entry or active efflux.
administration of the same dose; they are reached at 2 hours and average
~4 μg/mL when 250 mg is administered. Food does not interfere
with absorption. Perhaps because of more complete absorption of this
congener, the incidence of diarrhea with amoxicillin is less than that
following administration of ampicillin. The incidence of other adverse
effects appears to be similar. Although the t 1/2
of amoxicillin is similar
to that for ampicillin, effective concentrations of orally administered
amoxicillin are detectable in the plasma for twice as long as with
ampicillin, again because of the more complete absorption. About 20%
of amoxicillin is protein bound in plasma, a value similar to that for
ampicillin. Most of a dose of the antibiotic is excreted in an active
form in the urine. Probenecid delays excretion of the drug.
Therapeutic Indications for the Aminopenicillins
Upper Respiratory Infections. Ampicillin and amoxicillin are active
against S. pyogenes and many strains of S. pneumoniae and H.
influenzae, which are major upper respiratory bacterial pathogens.
The drugs constitute effective therapy for sinusitis, otitis media, acute
exacerbations of chronic bronchitis, and epiglottitis caused by sensitive
strains of these organisms. Amoxicillin is the most active of all
the oral β-lactam antibiotics against both penicillin-sensitive and
penicillin-resistant S. pneumoniae. Based on the increasing prevalence
of pneumococcal resistance to penicillin, an increase in dose
of oral amoxicillin (from 40-45 up to 80-90 mg/kg per day) for empirical
treatment of acute otitis media in children is recommended
(Dowell et al., 1999). Ampicillin-resistant H. influenzae may be a
problem in many areas. The addition of a β-lactamase inhibitor
(amoxicillin-clavulanate or ampicillin-sulbactam) extends the spectrum
to β-lactamase-producing H. influenzae and Enterobacteriaceae.
Bacterial pharyngitis should be treated with penicillin G or penicillin
V because S. pyogenes is the major pathogen.
Urinary Tract Infections. Most uncomplicated urinary tract infections
are caused by Enterobacteriaceae, and E. coli is the most common
species; ampicillin often is an effective agent, although resistance is