INTRODUCTION TO ANTIMICROBIAL
AGENTS
Antimicrobial
agents provide some of the most dramatic examples of the advances of modern
medicine. Many infectious diseases once considered incurable and lethal are now
amenable to treatment with a few pills. The remarkably powerful and specific
activity of antimicrobial drugs is due to their selectivity for targets that
are either unique to prokaryote and fungal microorganisms or much more
important in these organisms than in humans. Among these targets are bacterial
and fungal cell wall-synthesizing enzymes, the bacterial ribosome, the enzymes
required for nucleotide synthesis and DNA rep-lication, and the machinery of
viral replication. The special group of drugs used in mycobacterial infections.
The much older and less selective cytotoxic antiseptics and disinfectants..
The
major problem threatening the continued success of anti-microbial drugs is the
development of resistant organisms. Microorganisms can adapt to environmental
pressures in a variety of effective ways, and their response to antibiotic
pressure is no exception. An inevitable consequence of antimicrobial usage is
the selection of resistant microorganisms, perhaps the most obvious example of
evolution in action. Overuse and inappropriate use of antibiotics in patients
has fueled a major increase in prevalence of multidrug-resistant pathogens.
Antibacterial antibiotics are misused by providers in a variety of ways,
including use in patients who are unlikely to have bacterial infections, use
over unnecessar-ily prolonged periods, and use of multiple agents or
broad-spectrum agents when not needed.
As
a result of antibiotic pressure, highly resistant gram-negative organisms with
novel mechanisms of resistance are increasingly reported. Some of these strains
have spread over vast geographic areas as a result of patients seeking medical
care in different coun-tries. Much larger quantities of antibiotics have been
used in agriculture to stimulate growth and prevent infection in farm animals
and this has added to the selection pressure that results in resistant
organisms.
Unfortunately,
as the need has grown in recent years, develop-ment of novel drugs has slowed.
The most vulnerable molecular targets of antimicrobial drugs have been
identified and, in many cases, crystallized and characterized. Pending the
identification of new targets and compounds, it seems likely that over the next
decade we will have to rely on currently available families of drugs. In the
face of continuing development of resistance, considerable effort will be
required to maintain the effectiveness of these drug groups.
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