Elsewhere, I have discussed various approaches for
controlling urinary tract infections (UTIs) that help preserve the
effectiveness of life-saving antibiotics when they’re really needed.
This article extends this discussion with the intriguing idea that
innocuous bacteria can be used to fight-off UTI-causing pathogens.
As many PN readers know personally, UTIs are
an annoying, recurring health problem for individuals with SCI. It is
estimated that the incidence of UTIs with fever and chills in this group
is ~1.8 episodes annually (Arch Phys Med Rehabil 1993; 74(7)).
In the general population, most UTIs are caused by
E. coli bacteria, which, although a normal part of our intestinal
microflora, do not belong in our urinary system. In the case of SCI, a
diversity of other bacteria also causes UTIs.
Antibiotics
Because my doctoral studies investigated how
various antibiotics worked, I’ve especially appreciated their
life-saving importance and how careful we should be to maintain their
power.
Basically, antibiotic development became the
cornerstone in the establishment of the Paralyzed Veterans of America (PVA).
Like the hero in the Oscar-nominated movie Atonement, my g
reat-uncle
died due to infection from a wound he sustained charging a German
machine-gun nest in World War I. If antibiotics had been available, he
would have survived, and perhaps I would have met him.
A decade later, future Nobel Laureate Alexander
Fleming observed that bacterial growth was inhibited by a
penicillin-generating mold. As a result of his discovery and the ensuing
large-scale production of penicillin catalyzed by World War II’s
bloodshed, many soldiers wounded later in this war were able to live,
including PVA founders. Since then, scientists have developed numerous
antibiotics, which have greatly increased life expectancy after SCI.
Nevertheless, the growth of resistant bacteria is
of concern for the SCI population that relies on antibiotic use. For
example, research has shown every year two-million hospital patients get
infections that that they did not have when they entered the hospital;
of these, 80,000 die. Figures like these are especially pertinent to
infection- and hospitalization-prone individuals with SCI and underscore
the need to sustain antibiotic efficacy.
In spite of the perception that bacteria are the
“bad guys,” optimal health requires that we maintain a symbiotic,
health-enhancing partnership with them. For example, hundreds of
bacterial species living within our gut are essential for proper
digestion, nutrition, immunological development, and long-term health.
Every time we use an antibiotic, we undercut this bacterial partnership.
By constantly killing off the good guys as collateral damage, we create
a void that may be filled by pathogens or antibiotic-resistant bacteria
that now have no competition for growth. In spite of their clear
importance, antibiotics short-circuit your body’s inherent healing
potential. Tactically, you may be winning many health battles, but you
are weakening your defenses so much you may lose the war.
Because of these concerns, experts recommend that
antibiotics should be judiciously used, reserved for treating
symptomatic UTIs. The chosen antibiotic should be tailored to the
patient’s specific infection as determined by culture, and preferably a
single antibiotic should be administered.
Bacterial Interference
Bacterial interference is a potentially powerful
new approach for preventing UTIs and, by so doing, minimizing antibiotic
use. With this approach, innocuous bacteria are allowed to colonize the
bladder, competitively inhibiting growth by UTI-causing pathogens. Of
course, any antibiotic use during colonization would kill off the
protective bacteria.
Partially
funded by PVA, bacterial-interference studies have been carried out by
Dr. Rabih Darouiche and colleagues at
Baylor-College-of-Medicine-affiliated hospitals, including Michael E.
DeBakey VA-Medical Center and The Institute for Rehabilitation and
Research (TIRR) in Houston, Tex.
As reported in 2000, these investigators studied
bacterial interference in 22 subjects with SCI. All but three were men,
age ranged from 32 to 55 years, and the time lapsing from injury varied
from 5 to 24 months. Subjects were inoculated in the bladder using a
catheter with a benign E. coli strain. Long-term bladder
colonization with this strain (lasting from 2 to 40 months) was achieved
in 13 subjects. Although these subjects had averaged 3.1 symptomatic
UTIs annually before colonization, no infections were observed
afterwards as long as the colonization remained. In contrast, infections
were observed in patients who weren’t successfully colonized and those
who lost colonization.
The next year, the investigators reported the
results of a larger study involving 44 subjects with SCI. Of the 44
inoculated with the innocuous E. coli strain, 30 became colonized
and experienced while colonized a 63-fold reduction in symptomatic-UTI
incidence compared to their pre-study infection rate.
In 2005, the investigators reported the results of
a more rigorously designed randomized placebo-controlled, double-blind
pilot trial. Of the 21 patients whose bladders were inoculated with the
benign E. coli strain, all were men, average age was 52, and 10
and 11 had quadriplegia and paraplegia, respectively. Control subjects
were inoculated with a saline solution. The investigators concluded that
colonized subjects were half as likely as non-colonized patients to
acquire a UTI during the following year.
In a much larger randomized, double-blind,
placebo-controlled study scheduled for completion in 2008, 160 patients
with SCI or spina bifida are planned to be recruited from five medical
centers in Texas, Georgia, and Illinois. Because only about a third of
colonized subjects are expected to remain colonized for the 12-month
study period, subjects will be randomized in a 3:1 ratio. Subjects will
be treated with antibiotics before inoculation to eliminate preexisting
bacteria, and several days afterwards inoculated with the protective
E. coli strain or placebo.
The investigators also have studied bacterial
interference’s potential to reduce catheter-associated UTIs. Bacteria
that grow on implanted catheters can seed infections on an on-going
basis. The investigators concluded that pre-exposure of the catheter to
benign E. coli significantly reduced catheter colonization by UTI-causing
bacteria.
Conclusion
All life exists in equilibrium with a greater
whole. Whenever we myopically damage one piece of this whole to benefit
another, we create a new equilibrium, which may not be so life-enhancing
over the long term. As an analogy, if we indiscriminately clear-cut our
forests to benefit our immediate needs, we know it’s going to hurt us
down the road as nature attempts to re-equilibrate. Likewise, if we
continuously clear-cut our health-sustaining, bacterial microflora
through repeated antibiotic use, it will inevitably adversely affect us.
By reseeding the bladder with innocuous bacteria after antibiotic
clear-cutting, we create a more health-sustaining environment.
Adapted from article appearing in Paraplegia News (For subscriptions,
go to www.pn-magazine.com).
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