By Ron Najafi, PhD
Patients fitted with long-term indwelling bladder catheters often face a serious complication: bacteria, most commonly Gram-negative Proteus mirabilis, can easily colonize and encrust the catheter. This eventually leads to the formation of a crystalline biofilm, consisting of mucopolysaccharide, that blocks the normal flow of urine from the bladder. Current methods for unblocking encrusted catheters by mechanical means, such as saline solution, replacing the catheter, or by using agents that try to dissolve the biofilm crystals, do not provide satisfactory results.
What about using antibiotics to keep the bacteria away from the catheter? There is a problem with this approach as well. Encased in its biofilm, bacteria can survive for prolonged periods by assuming a dormant state. When in this form, they are largely immune to antibiotics, which are generally only effective during specific non-dormant stages in a bacteriums life cycle. And there is the specter of antibiotic resistance to consider as well. In this era of "superbugs," one must take into account the very real damage that antibiotic-resistant bacteria can do to catheterized patients.
The blockages can lead to incontinence as well as increased risks of developing bacteriuria, pyelonephritis, bacteremia and sepsis. More than 300,000 patients suffering from spinal cord injury such as quadriplegia, paraplegia or stroke and multiple sclerosis who are using catheters are at daily risk for developing one of these catheter-associated urinary tract infections. One-third of this population is contaminated with P. mirabilis.
Luckily, a new approach is now offering the potential of eliminating the P. mirabilis¬ and the biofilm without raising the danger of antibiotic resistance. In a recent study that was presented at this years Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), a team led by Dr. Dmitri Debabov investigated the potential use of a non-antibiotic anti-infective compound to resolve the issue of biofilm formation on catheters. What is the rationale behind harnessing a non-antibiotic compound in this way? Such a compound mimics the human bodys own natural defenses against infection. Since our immune system works without ever creating resistance, there is great potential for studying the effective and rapidly acting molecular defenses that function within us and creating stable analogs of these molecules.
As reported at ICAAC, the Debabov team created lab models of catheterized bladders that were filled with urine and populated by P. mirabilis. Then either the anti-infective compound or saline (as a control) was instilled on a regular basis into the catheterized bladder chambers for up to 144 hours, or until the catheters became blocked. The formation of a biofilm in each case was carefully observed. The researchers found that the catheters irrigated with pure saline became blocked 46 hours after the start of the experiment, and electron microscopy confirmed that the blockage of those catheters was due to the accumulation of biofilm.
In contrast to the saline, a 0.2 percent solution of the anti-infective compound kept the catheter unblocked for the entire 144-hour test period, and no biofilm was visible. The researchers concluded that a bladder washout regime using their compound could be used to manage catheter encrustation.
This positive result raises the possibility of a new class of potent, fast-acting, broad-spectrum antimicrobial agents that can kill P. mirabilis and thereby inhibit the formation of struvite crystals in the catheter, minimize any subsequent catheter blockage and ward off the tract infections it can triggerall without providing the opportunity for antibiotic resistance to develop. Should the ICAAC result be replicated on a larger scale and commercialized, it could mean the dawn of a new era for those patients whose conditions require catheterization as well as for those who care for them.
Ron Najafi, PhD is chairman and CEO of NovaBay Pharmaceuticals, an Emeryville, Calif.-based biotechnology company developing anti-infective compounds for the treatment and prevention of antibiotic-resistant infections. He can be reached at [email protected]