Dear Editor:

       The article by Serena et al (Lack of reliability in clinical/visual assessment of chronic wound infection: the incidence of biopsy-proven infection in venous leg ulcers), which appeared in the July 2006 issue of WOUNDS, is open to a very different interpretation—that the repeated biopsies and courses of antibiotics caused the delay in healing. After all, the venous ulcers started with < 10⁵ CFU, their “definition” of infection, so “infection” could not have been the cause. Incidentally, the specificity, sensitivity, discriminatory value, and positive and negative predictive validity of the 10⁵ “definition” of infection leave much to be desired. By that definition, much of the normal human skin is “infected,” but that is a separate issue for others to address.
       Nemeth et al¹ showed that biopsies can take more than 3 weeks to heal.
       Ennis and Meneses² showed that antibiotics are associated with delayed leg ulcer healing.
       The combination to which Serena et al describe repeatedly subjecting their patients may have placed these patients with multiple biopsies in greater jeopardy of delayed healing with each successive biopsy.
       Biopsies and antibiotics may be more harmful than we have supposed. As an alternative, clinicians may consider the swab approaches described by Dow³ or Thomson and Smith.⁴

Laura L. Bolton, PhD, FAPWCA
Adjunct Associate Professor
Department of Surgery
University of Medicine & Dentistry of New Jersey
New Brunswick, NJ



Dear Editor:

       I want to thank Dr. Bolton for her excellent comments. The main purpose for publishing this article was to demonstrate that clinical assessment is unreliable in determining the presence of infection in venous leg ulcers. Our results clearly confirm this suspicion.
       We used the accepted standard for wound infection (>10⁵ cfu/g of tissue) because the largest body of evidence in the literature supports this definition. The evidence for alternative techniques is sparse and the use of any nonquantitative measure would be unreliable at best.
       Dr. Bolton suggests that there are alternative explanations for why the patients with positive biopsies at screening who were subsequently enrolled in the trial (after a negative biopsy) tended to heal more slowly. There are multiple possible explanations. I agree with Dr. Bolton that it was not the infection per se that slowed the healing because the biopsies were negative at the time of enrollment into the trial. It seems most likely that the infection resulted in an impairment of healing by some mechanism, such as an increase in matrix metalloproteinases. The suggestion that antibiotics may have played a role in delayed healing is interesting; however, there was no uniformity in the treatment regimen for the infected ulcer—this was left to the discretion of the investigator. Patients were treated with oral antibiotics and/or topical agents. Some of the patients with infection did not receive antibiotics at all. Unfortunately, the treatments were too varied and the sample size is too small to draw any further conclusions.  
       The premise that repeated biopsies may have interfered with the healing process is less likely. Biopsies may take time to heal but there is no evidence that this is accompanied by a delay in overall healing time. In my experience wound biopsy tends to act more like debridement—stimulating wound closure.
       The points raised by Dr. Bolton point to the need for further research into the complex interplay between wound healing, infection, and bacterial burden.

Thomas E. Serena, MD, FACS
Medical Director
Penn North Centers for Advanced Wound Care
Warren, Pa