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Letter to the Editor: Reconsidering the 10(5) Rule
Dear Editor,
Regarding the article, “The 105 Bacterial Growth Guideline: Reassessing its Clinical Relevance in Wound Healing” (Ostomy/Wound Management. 2003;49[1]:44–53), the interrelationships among micro-organisms and host resistance are well-known and accepted, and the author correctly notes the need to understand these relationships in comprehending the complexities of soft tissue infections. However, his perusal of selected articles on quantitative bacteriology and its usefulness leaves the reader with several injudicious conclusions.
The two major monographs on bacterial balance1,2 contain the same discussions presented by Bowler, including sections on virulence, pathogenicity, host defense mechanisms, and antimicrobials. The main differences between those monographs and the Bowler article are the inclusion of hard data.
It is a biological fact that a balance or equilibrium exists between bacteria and host resistance factors, and when equilibrium is upset in favor of the bacteria, potential for infection occurs. In all of the studies reviewed since the turn of the 20th century, the balance fulcrum is at approximately 1 million organisms per gram of tissue or mL of biologic fluid. The numerical distribution, like all biologic phenomena, forms a bell-shaped curve. Therefore, some infections might be expected to occur with fewer numbers of bacteria, and occasionally, no infection will be present when large numbers of bacteria are noted.
All of the data published suggest that 105 or fewer bacteria per gram of tissue are compatible with normal wound healing. Bowler explains how quantitative bacterial analyses are performed and, therefore, realizes that >105 means beyond that exact tube dilution or at least 1 x 106.
The real problem with the article is the suggestion that the bacterial balance concept using a numerical bacterial burden is not clinically relevant. In the original study performed on wound closure by skin grafts, 94% of grafts were successful when wounds contained 105 or fewer bacteria per gram of tissue; while only 19% were successful when 105 bacteria per gram were present.3 This is clinically relevant. In the next study4 of wound approximations, 28 out of 30 wounds were successfully closed when the wounds contained 105 or fewer bacteria; whereas, 0 out of 10 wounds were successfully closed when >105 organisms/gram were present, which is clinically relevant. Specialists dealing with acute and chronic wounds have reported similar data. In one monograph,2 the data are referenced for chronic wounds, general surgery, orthopedic surgery, plastic surgery, thoracic surgery, and burns. In each case, the usefulness of the numerical concept of evaluating the bacterial equilibrium is validated as to clinical relevance. Bowler suggests that surgeons may find these principles more useful because their views might differ from those of a microbiologist. All of the studies on quantitative bacteriology from our laboratories included a microbiologist (John P. Heggers, PhD). In fact, Dr. Heggers is the senior author of the above-mentioned monograph.
Bowler specifically states that the venous stasis ulcer is a polymicrobial-contaminated wound and questions the value of quantitative bacteriology. Two recent articles may be of interest. In a review of data from a clinical trial of repifermin (KGF-2), Falanga5 showed that the number of bacteria at the time of initial screening affected the response to growth factors (ulcers with less than 1 x 106 bacteria per gram of tissue at screening fared better). Similarly, Sibbald,6 reporting on the treatment of chronic wounds with cell-based therapies, found that wounds not in bacterial balance did not respond as well.
Bowler suggests that clinical signs of infection (inflammation, pain, edema, and suppuration) may be more useful than the microbial load. Clinical signs are usually late indications that occur when large quantities of bacteria are present, especially when Gram-negative organisms predominate. In the first study3 using bacterial quantification to evaluate skin graft “take,” grafts were only applied when the wounds were clinically ready for grafting (ie, no inflammation, pain, edema, or suppuration). Yet in 50% of the cases, these clinically “healthy” wounds contained 105 bacteria per gram and skin grafts did not “take.”
Finally, regarding swabs versus tissue biopsies, several meticulous semi-quantitative techniques have been described and could be useful.2 However, when comparing use of routine swabs and tissue biopsies, in 367 cases, the same organism was obtained in only 22% of the cases.
Before deciding the concept of quantitative bacterial burden is not clinically relevant, the data (albeit overwhelming) should be evaluated. Bowler’s principles are excellent and need to be considered. Qualitative, as well as quantitative, bacterial analyses must be performed under both aerobic and anaerobic conditions. To best put this in perspective, consider this statement by Edlich et al7: “Interestingly, the type of obligate aerobes and facultative species contaminating the wound surface plays a lesser role in the development of infection than does the quantity of bacteria. If large numbers of indigenous or commensal bacteria (105 per gram of tissue) reside in the wound, infection will develop.”
Martin C. Robson, MD
Emeritus Professor of Surgery
University of South Florida
References
1. Robson MC, Krizek TJ, Heggers JP. Biology of surgical infection. Monograph. In: Ravitch MM, ed. Current Problems of Surgery. Chicago, Ill: Yearbook Medical Publishers, Inc:1973.
2. Heggers JP, Robson MC. Quantitative Bacteriology: Its Role in the Armamentarium of the Surgeon. Boca Raton, Fla: CRC Press:1991.
3. Krizek TJ, Robson MC, Kho E. Bacterial growth and skin graft survival. Surgical Forum. 1967;18:518–519.
4. Robson MC, Lea CE, Dalton JB, et al. Quantitative bacteriology and delayed wound closure. Surgical Forum. 1968;19:501–502.
5. Falanga V, Odenheimer D, Bagchi P. Repifermin (KCF-2) is able to reverse delayed healing in patients with high bacterial burden at presentation. Wound Rep Regen. 2001;9 (abstract).
6. Sibbald RG, Williamson MB, Orsted HL. Preparing the wound bed — debridement, bacterial balance, and moisture balance. Ostomy/Wound Management. 2000;46:14–35.
7. Edlich RF, Rodeheaver GT, Thacker JG, et al. Management of soft tissue injury. Clin Plast Surg. 1977;4:191–201.
Reply
Undoubtedly, clinical evidence supports the view that bacterial numbers play an important role in wound healing. The intention was not to discredit the clinical relevance of quantitative bacterial burden, but rather to place it in context with other aspects of wound microbiology in view of scientific research and knowledge that have evolved over the last decade.
Bacteria should not be underestimated. They may be small and simple in structure, but they are highly adaptable, unpredictable, and varied, and they can change quickly from a non-pathogenic to a pathogenic state. If clinicians acknowledge Dr. Robson’s statement, “If large numbers of indigenous or commensal bacteria (>105 per gram of tissue) reside in the wound, infection will develop” the variability, capability, and unpredictability that exist between and within bacterial species may be discounted, as well as the subsequent threats they pose.
The original article equally challenged qualitative microbiology. The literature indicates the correlation between specific bacteria and infection is poor. However, when different bacterial species are brought together, as is common in wounds, their combined effect becomes more problematic.1,2 This occurs as a consequence of bacterial communication and interactions that subsequently increase their virulence capacity and probability of survival. Bacterial synergy is one form of interaction (noted in the article) and quorum sensing is another. This latter microbial process involves bacteria recognizing an appropriate time point to attack the host by releasing signal molecules when a “quorum” (ie, a minimum population density) is reached. A change in bacterial response at this quorum level normally involves the increased production of virulence factors such as enzymes and biofilms. In this respect, quorum sensing may explain the 105 clinical observations in wounds. However, quorum sensing is a complex process and involves bacteria communicating between and within species, and threshold densities are likely to vary between species and in relation to the types of organisms present. As indicated in the article, the infective dose of an anaerobe was reduced from >106 cfu to <10 cfu when a subinfectious dose of Escherichia coli was co-administered subcutaneously in mice.3 Clearly, combinations of interacting bacteria can alter the infectious dose. My view, therefore, is that bacterial numbers and types should be considered collectively rather than in isolation and that a more balanced analysis of wound microbiology is essential.
Regarding the value of clinical signs of infection versus the wound microbiology, microbiology plays a supportive role in clinical diagnosis. However, because bacteria may be problematic without causing clinical signs of infection, for grafting or for the application of “high tech” and expensive products such as skin equivalents, reducing the bioburden to non-problematic levels before treatment is important.
With respect to the merits of superficial swabbing versus tissue biopsy, debate is likely to continue. Although Dr. Robson provides an example of the poor correlation between organisms recovered by the two sampling methodologies, recent studies have shown much higher correlation between quantitative tissue and swab counts4 and quantitative and semi-quantitative swab counts.5
Dr. Robson’s and my opinions are not markedly different, although I believe that a balanced awareness of the interrelationships that exist between bacterial numbers and species in wounds is extremely important to the practitioner managing problem wounds.
Philip G. Bowler, MPhil, BScD
References
1. Trengove NJ, Stacey MC, McGechie DF, Mata S. Qualitative bacteriology and leg ulcer healing. J Wound Care. 1996; 5:277–280.
2. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Micro Rev. 2001;14:244–269.
3. Smith GR, Till D, Wallace LM, Noakes DE. Enhancement of the infectivity of Fusobacterium necrophorum by other bacteria. Epidemiol Infect. 1989;102:447–458.
4. Bill TJ, Ratcliff CR, Donovan AM, Knox LK, Morgan RF, Rodeheaver GT. Quantitative swab culture versus tissue biopsy: a comparison in chronic wounds. Ostomy/Wound Management. 2001;47:34–37.
5. Ratliff C, Rodeheaver GT. Correlation of semi-quantitative swab cultures to quantitative swab cultures from chronic wounds. Wounds. 2002;14:329–333.
