VANCOUVER, B.C. — If physicians had a better understanding of the bacteriology of chronic wounds, they would stop overprescribing antibiotics for this indication—a strategy that rarely works and contributes to antibiotic resistance.
That's the assessment of Brian Kunimoto, M.D., director of the Wound Healing Clinic at the Vancouver Hospital and Health Sciences Centre and a member of the dermatology faculty at the University of British Columbia in Vancouver.
“Is there a problem with bacteria that grow in wounds, convincing some of us to do silly things like order useless tests, and worse yet, actually act on such useless information … [by] prescribing drugs that have no chance of working? I think it's a big problem, and it has nasty consequences,” said Dr. Kunimoto at the annual meeting of the Pacific Dermatologic Association.
Wounds come in many forms, with bacteria acting as attackers that have more or less of an impact depending on the vulnerability of the host as well as their own numbers and virulence, he said. (See chart.)
When bacteria are planktonic, they live an independent, nomadic life, disorganized and generally in a fluid state. In this form, they pose little threat to a human host.
However, when they begin to unite in an organized, adherent, cooperative “city-state,” they form a biofilm that poses a considerable challenge to physicians, Dr. Kunimoto said. Approximately 65% of all bacterial skin infections are related to biofilms characterized by their creamy, adherent properties.
“You brush off a biofilm every night when you brush your teeth. The classic biofilm is plaque on your teeth,” he said.
Biofilms, he explained, are made up of an exopolysaccharide matrix that allows for intracellular communication, production of a food supply, an escape route for waste, and most troubling, the sharing of genetic information.
A biofilm is polymicrobial, allowing for a harmonious existence of many forms of bacteria.
“I think bacteria do a better job at multiculturalism than our country, Canada,” he mused.
Culturing a biofilm is useless, he maintained. “It's no different from culturing your nose. You will find—wow!—bacteria! It gives us no really useful information.”
A culture may identify some bacteria present in the biofilm, but it will not characterize the rich and diverse population flourishing in a wound.
Moreover, neither topical nor systemic antibiotics penetrate a biofilm effectively, so they will be impotent, or worse, will provide highly useful resistance information to bacteria essentially sharing a bulletin board in a bustling city.
The best clinical practice for attacking biofilms is relentless debridement, according to Dr. Kunimoto.
“As I say to the residents in the clinic, 'Don't slough sloughing the slough.'
“Don't throw an antibiotic at this. Get out your tools and dig away. Don't give up,” he said.
Several antimicrobial agents can be used as adjuncts, including silver, starch iodine, and even manuka honey.
But the most critical treatment is repeated debridement, performed, if necessary, after a lengthy (2–3 hour) application of a topical anesthetic such as EMLA, he said.
Antibiotics are of use only in true clinical infections.
Nitric Oxide Gas Wards Off Bacteria
In the frustrating war against chronic wounds, Brian Kunimoto, M.D., and associates at the University of British Columbia think they may have found a secret weapon that comes in a tank.
It's nitric oxide gas.
A naturally produced, lipophilic molecule, nitric oxide, unlike antibiotics, easily penetrates biofilms, well-organized populations of bacteria that can form in chronic, difficult-to-heal wounds.
“I call it a smoking gun,” said Dr. Kunimoto, director of the Wound Healing Clinic at Vancouver Hospital and Health Sciences Centre.
He explained that nitric oxide combines with reactive oxygen to create “an entire soup of bacteriocidal intermediates” in a wound, and poisons the iron enzyme aconitase.
In the presence of this onslaught, “unless a bacterium can quickly develop into an anaerobic organism, it will die,” he said at the annual meeting of the Pacific Dermatologic Association.
Nitric oxide also deaminates DNA and enhances the damaging effects of hydrogen peroxide when it is present as a reactive oxygen intermediate.
Studies at the University of British Columbia found that counts of bacteria, including Staphylococcus aureus, pseudomonas, and methicillin-resistant S. aureus, plummeted to zero within hours of exposure to gaseous nitric oxide.
Home therapy involving nighttime exposure to the gas quickly healed a 2-year-old, nonhealing ankle ulcer in a 55-year-old man with severe venous disease, said Dr. Kunimoto, who recently published the case (J. Cutan. Med. Surg. 2004;8:233–9).
“This is remarkable for this gentleman, [considering] we worked on him for 2 years and got nowhere,” he said. “We've shifted the balance in favor of the host.”