A recently released study by The Centers for Disease Control and Prevention (CDC) revealed that the number of diagnosed cases of diabetes rose by a third (from 4.9 to 6.5 percent) between 1990-1998. This percentage will increase to 9 by 2025. The breakdown of cases by age was particularly alarming. The incidence of diabetes increased 40 percent over a period of eight years for people 40 and over. It increased 70 percent for people 30 and over. This is of serious concern when you consider the resulting complications that may be prevalent earlier in life and the exuberant medical care costs that run from $10,000 to $12,000 annually for the remainder of the patient’s life. Many studies have shown the per capita medical costs for a patient with diabetes are three times that of those for a person without diabetes. About 15 percent of people with diabetes mellitus develop foot ulcerations at some point in their life.1 Additionally, many of those who develop ulceration will go on to osteomyelitis.2 Foot infections are a leading cause of hospital admissions in people with diabetes and a major cause of lower extremity amputations. With the increased risk of complications and the increase in care costs, effectively diagnosing and treating diabetic infections has become more important than ever. Key Diagnostic Pointers And Early Treatment Considerations Early recognition of diabetic foot infections goes a long way toward treatment success. Most diabetic foot infections originate with the breakdown of the soft tissue envelope. This breakdown is mechanical. It is caused by the lack of normal protective sensation, which allows unrecognized trauma or microtrauma to cause tissue edema, inflammation and necrosis. Once the dermal barrier has been broken, there is a resulting open portal for infection of the deep tissue.3 The diabetic foot is a fertile ground for a number of infectious complications such as: • epidermophytosis; • bacterial soft tissue and bone infection; • severe fungal infections (allow ubiquitous bacteria to become invasive); and • dermatophytes. Early in the treatment plan of a diabetic foot infection, you must answer two important questions: • Is hospitalization required? • Is surgical intervention necessary? A simple way to summarize widely practiced surgical and medical therapies is the 4-D approach for abscess: decompression, drainage, debridement and drugs. Exploring Alternative Therapies In addition to traditional antibiotic and surgical decompression, there are many emerging adjunctive modalities to aid in the treatment of diabetic foot infections. The therapies include larval (maggot) therapy and granulocyte colony-stimulating factor. Maggot debridement therapy is an inexpensive and efficient adjunct for treating diabetic foot wounds.4 Researchers have found that maggots are useful in debriding wounds, controlling wound odor and reducing bacterial burden in wounds, even in wounds infected by antibiotic resistant organisms. Maggots are fly larvae and are available in medical grade from commercial laboratories in the United States and Europe. This treatment is currently used in several centers, but requires proper staff training and patient acceptance. Evidence-based trials are also needed to appropriately define what type of infections would benefit from this therapy. A preliminary randomized controlled study showed that adding subcutaneous injections of recombinant granulocyte colony-stimulating factor (G-CSF) to local wound care and antibiotic therapy led to significantly more rapid infection resolution and better outcomes in diabetic patients with serious foot infections.5 However, another randomized controlled trial found there was no significant benefit to adjuvant G-CSF in patients with limb-threatening diabetic foot infections.6 Larger trials are needed to determine how effective this expensive drug can be in treating diabetic foot infections. Surveying The Antibiotic Possibilities Antibiotic-impregnated calcium sulphate pellets have been used for the local treatment of deep, infected, diabetic foot wounds with or without osteomyelitis. The qualities of biocompatibility and biodegradability along with a slow release of high levels of a locally concentrated antibiotic make the pellets a beneficial therapy. This product is now commercially available in a kit that consists of the powdered calcium sulfate and a curing solution. The one time use kit is prepared under sterile conditions in the operating room and a powdered antibiotic (i.e. 500 mg of vancomycin prior to hardening) is added. The mixture is then placed into a formation template to fabricate pellets of various sizes from 3 to 6 mm. The curing takes less than two minutes. You would place the radiopaque pellets in the open wound prior to closure. The pellets are resorbed completely over approximately six weeks and deliver a steady state antibiotic concentration directly to the wound site. Controlled studies are necessary to determine the efficacy of this modality in treating diabetic foot infections, but early clinical results have been impressive. Empiric antibiotic therapy should include broad spectrum antibiotics capable of covering the most common pathogens found in diabetic infections. Empiric treatment of moderate to severe infections should include agents active against Staph, Strep, gram-negatives, bacilli and anaerobes. Single agents include carbapenems or beta-lactam/beta-lactamase inhibitor combinations such as piperacillin/tazobactam (Zosyn), ticarcillin/clavulanate (Timentin) or ampicillin/sulbactam (Unasyn), imipenem/cilastin (Primaxin), vancomycin, anminoglycosides and ertrapenem (Invanz) given IV. Combination therapy often includes clindamycin in addition to the previously mentioned antibiotics. In a study to be published in the near future, linezolid (oral) was proven to be at least comparable to aminopenicillins (IV) in a randomized international multicenter trial.7 (See “New Study Reveals Promise Of Linezolid For Diabetic Infections,” News And Trends, December 2002 issue.) Final Notes Overwhelming evidence suggests that by striving to ensure optimal glucose control, proper wound care and appropriate surgical and antibiotic therapy, one can control diabetic foot infection and preserve a functional foot in most patients. The current challenge is to not only continue to develop new treatments but to master existing ones in a cost-effective, evidence-based and multidisciplinary manner. Not only should we collaborate with various medical specialists, we must also recognize that the patient is the most important member of the team in order to win the battle of saving limbs. Dr. Jones is a first year resident at the University of Texas Health Science Center in San Antonio, Texas. Dr. Steinberg is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.
References 1. Lipsky BA. Osteomyelitis of the foot in diabetic patients. Clin Infect Dis 1997; 25: 1318-1326. 2. Caputo GM, Cavanagh PR, Ulbrecht JS, et al. Assessment and management of foot disease in patients with diabetes. N Engl J Med 1994; 331: 854-860. 3. Brodsky JW, Schneidler C. Diabetic Foot Infections. Ortho Clin of North America. 1991; 22:3 473-489. 4. Armstrong DG, Mossel J, Short B, Nixon BP, Knowles EA, et al. Maggot debridement therapy: a primer. JAPMA. 2002; 92:7 398-401. 5. Gough A, Clapperton M, Rolando N, et al. Randomized placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infections. Lancet. 1997; 350: 855-859. 6. De Lalla F, Pelizzer G, Strazzabosco M, et al. A randomized prospective controlled trial of granulocyte-colony stimulating factor (G-CSF) in limb-threatening diabetic foot infections. 7. Lipsky BA. Abstract: Treating Diabetic Foot Infections with Linezolid vs. Aminopenicillins: A Randomized International Multicenter Trial. Additional Reference 8. Levin and O’Neal’s The Diabetic Foot. Edited by Bowker JH, Pfeifer MA. Sixth ed. 2001.