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 readers know personally, UTIs are an annoying, recurring health problem for individuals with spinal cord injury (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.
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 great-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 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.
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 June 2008 PN/Paraplegia News article)
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