WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, Dr. Randall Wolcott said at a meeting sponsored by George Washington University Hospital.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease. He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis.

This translates to more than 500,000 people a year who die from a biofilm disease, and it is time practitioners realized that the infected diabetic foot wound is a biofilm disease as well, in order to treat it appropriately, said Dr. Wolcott of the department of microbiology and immunology at Texas Tech University, Lubbock, and the Southwest Regional Wound Care Center in that city.

He used the dramatic imagery from the science fiction movie “Terminator II,” in which a killer police officer, made of liquid metal, is first shattered into pieces and yet quickly reassembles with equal destructive capability as before.

The behavior of biofilms is similar, he pointed out. Once bacteria attach to a wounded surface, “they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses,” he said.

This vegetative state behaves like a single organism “made of billions of billions of cells” including multiple bacterial species. A large portion of this “organism”—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell “seeds.” The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins, just as organisms have different brain cells, liver cells, and so on. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

This understanding is very new, Dr. Wolcott said. “I just got a [2007] medical microbiology text and it does not mention biofilms,” he noted, suggesting maybe that was why most of the audience might not have heard of these concepts.

However, practitioners did see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, Dr. Wolcott added. Many believe slough is merely some mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return exactly as before if even “one cell remains” still virulent, exactly as before without proper treatment.

“If I take off waxy biofilm … then I get waxy biofilm back. If I take off the fluffy biofilm I get the fluffy,” he said. “So slough really is biofilm.”

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said. This combined treatment is only in its infancy. It involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

In his practice, he also thinks it critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, “once you suppress the biofilm below a certain level … the wound starts contracting” and normal host healing can begin, he said.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

Take a Biofilm Approach To Infected Foot Wounds