INTRODUCTION
The successful treatment of bacterial infections improved
significantly after sulfonamides were discovered
to possess antibacterial properties in the late
1930s and especially when penicillin became available in the
mid-1940s. The effect of penicillin on Streptococcus pneumoniae,
the then leading cause of infectious disease and
death worldwide,1 was particularly dramatic. However, within
a relatively short period of time after antimicrobial drugs were
introduced, bacteria began responding by exhibiting various
forms of resistance. This author is among many worrying
about the issue of antibiotic resistance. This problem is
expanding in scope (number of different organisms exhibiting
resistance, number of antibiotic agents for which resistance
mechanisms are spreading) and in dimension (number
of places worldwide where antibiotic resistance is prevalent).
In fact, the ever-increasing problem of antibiotic resistance
is viewed today as a serious threat to global public health.2
The problem has become sufficiently severe as to lead to this
alarming quotation: “It has been a rarity for a physician in
the developed world to have a patient die of an infection for
which there are no therapeutic options. These cases highlight
troubling issues that soon might soon be relevant across the
Untied States.”3
The excessive use and misuse of antibiotics in humans, animals
and agriculture are critical factors driving a growing resistance
problem. The widespread availability of various inexpensive
antibiotics has made it all too easy for patients to request, or to
demand, antibiotic treatment, and for physicians to prescribe
antibiotics for incompletely evaluated or unspecified infections,
or for unverified disease states.
What Are the Mechanisms of Resistance?
Antibiotic resistance occurs when strains of bacteria no longer respond
to antimicrobials used to treat infections caused by those
microbes. Although some species of bacteria are inherently resistant
to one or more classes of antimicrobial drugs, cases of acquired
resistance in populations of bacteria that were once susceptible are
of greater concern.4 Basic microbiology dictates that use of antibiotics
significantly reduces the population of antibiotic-susceptible
strains, resulting in the selective survival and multiplication of
resistant organisms. Such organisms thrive due to reduced micro-environmental competition for essential nutrients and water.
Resistant organisms can also transfer genetic material to other
species, which exacerbates the problem by leading to an increased
number and variety of microbes demonstrating resistance.4,5
Antimicrobial resistance can occur via several mechanisms,
including: prevention of the ingress of the antibiotic into the
target organism's cytoplasm, alteration of or compensatory
over-elaboration of the antibiotic target, destruction of the antibiotic,
or enhanced function of microbial efflux pumps (wherein
the organism pushes the antibiotic out of the cell).4 Normally
susceptible groups of bacteria may become resistant to antimicrobial
agents via random mutation or by acquisition of genetic
information that encodes resistance from other, unrelated bacteria.
Many bacteria have become resistant to multiple classes
of antibiotics via genetic exchange mechanisms.4
