With the discovery of antibiotics the world changed. Acute infectious diseases, the leading cause of morbidity and mortality in humans, became treatable, resulting in an increase in life expectancy and quality of life.
TOLERANCE OF BIOFILMS TO ANTIMICROBIALS
With the discovery of
antibiotics the world changed. Acute infectious diseases, the leading cause of
morbidity and mortality in humans, became treatable, resulting in an increase
in life expectancy and quality of life. While infections continue to be a
leading contributor to mortality, they are often associated with pre-existing
conditions that compromise the patient. However, what became known as the ‘antibiotic
era’ is now being compromised itself by the emergence of more and more
antibiotic-resistant strains of bacteria that have caused modern medicine to
question if we are not now entering the ‘post-antibiotic era’.
What is often ignored in
these discussions of antimicrobial resistance and our reduced ability to treat
infection is the fact that even in the halcyon times of antimicrobial therapy
chronic or recurrent infections were poorly resolved with antibiotics. In fact,
the designation of these infections as chronic was presumably derived due to
their lack of responsiveness to antimicrobial therapy allowing them to become
chronic or to recur in the face of therapy. Diseases such as recurrent ear
infections in children, recurrent UTIs in women, and medical device-associated
infections were and still remain a challenge to antimicrobial therapy, even
when the isolates of these infections have been shown in vitro to be susceptible to antibiotics used in their treatment.
It is now recognized
that these chronic infections involve bacteria associated within biofilms. In
fact the US Food and Drug Administration (FDA) and Centers for Disease Control
(CDC) both state that more than 60% of North American infections involve
biofilms. We also now recognize that the confounding issue in the treatment of
chronic infections is the inherent tolerance of biofilms to antibiotics
predicted to have efficacy against the organism on the basis of planktonic
susceptibility testing. In fact, Ceri and colleagues demonstrated that for an antibiotic
to be effective in biofilms can require a concentration over 1000 times that
needed to treat the same planktonic population (Ceri et al. 1999); concentrations that cannot be achieved or used safely
in patient treatment. This altered tolerance to drugs is an adaptation of the
biofilm, as bacteria derived from the biofilm show the same susceptibility
profile as planktonics when the organisms are returned to the planktonic growth
phase.
This reduced
susceptibility to antibiotics differs from antibiotic resistance in a number of
fundamental ways. First, this tolerance is only demonstrated when the isolate
is in the biofilm mode of growth and is lost when the culture is returned to
planktonic growth, hence it is not a permanent genetic change. Secondly,
tolerance implies that the biofilm is not killed by the antimicrobial but it
may not necessarily be able to grow in the presence of the drug, whereas in
resistance the organism can grow in the presence of the antimicrobial. The
tolerance of biofilm populations to antimicrobials would imply that in many
instances of chronic infections microbes are in fact exposed to sublethal
concentrations of drug, which may be an important implication in the
development of classical antimicrobial resistance.
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