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Abstract
In most cases antimicrobial combinations are employed to broaden the spectrum of coverage.
This clinical application is likely to be successful as long as the combinations are
not antagonistic. Most examples of antibiotic antagonism are those in which a bacteriostatic
agent renders a bactericidal agent “static.” Another type of antagonism occurs when
cefoxitin (which has a propensity to induce beta-lactamase production) is combined
with another beta-lactam antibiotic. Combination drug therapy prevents emergence of
resistant strains in mycobacterial infections and in infections due to methicillin-resistant
staphylococci and certain other resistant organisms. Synergistic combinations should
allow the use of lower concentrations of drugs in combination and thus diminish the
incidence of dose-related antibiotic toxicity, but the concept has met with only limited
success so far. Three types of antimicrobial combination or interaction result in
enhanced (synergistic) antimicrobial activity. These types include combinations of
agents that inhibit bacterial cell wall synthesis with aminoglycosidic aminocyclitols,
the use of beta-lactamase inhibitors in combination with beta-lactam antibiotics,
and the administration of agents that act on sequential steps in one of the bacterial
metabolic or synthetic pathways. Combinations of two beta-lactam antibiotics that
bind to complementary penicillin-binding proteins may represent an analogous situation.
Amdinocillin binds specifically to penicillin-binding protein 2, and in vitro studies
have clearly demonstrated synergism when amdinocillin is combined with other penicillins
and cephalosporins that have higher affinity for other penicillin-binding proteins.
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© 1983 Published by Elsevier Inc.
