Serious foot infections result from a combination of factors including disease, injury, neuropathy, vascular impairment and insufficient wound healing. Diabetic patients, in particular, are at high risk of developing serious complications in lower extremities that can lead to amputation. Of the estimated 17 million people who have Type 1 and Type 2 diabetes, almost 15 percent will undergo lower extremity amputation during their lifetime.1,2 Approximately 80 percent of diabetes-related amputations are preceded by chronic foot ulcers.3-5 Many chronic foot ulcers in diabetics are the result of lower extremity infections. In addition to patients with diabetes, immunocompromised patients and those who have peripheral vascular disease frequently suffer lower extremity complications because of fungal and bacterial infections. Fungal infections of the skin and nails are commonly seen as the underlying basis for tinea pedis and other fungal and bacterial infections.6 Approximately 30 percent of patients with diabetes have disease-related dermatologic problems.7 Fungal and bacterial infections, as well as candidiasis, most often occur as opportunistic or secondary infections in patients who are already compromised or susceptible to infection. One of the most common fungal infections we see is tinea pedis.8 More common in adolescents and adults than in children, this superficial skin infection typically involves the interdigital spaces and may present as dermatophytosis simplex or dermatophytosis complex with a possible secondary bacterial infection.9-11 We also see quite a bit of chronic paronychia, onycholysis and onychomycosis, common dermatological nail disorders that require a comprehensive and prophylactic management approach to arrive at optimal clinical outcomes and reduce the risk of chronic presentation.12,13 Although nail infections are preceded by a dermatophyte, the symptomatic patient may have a more complex infection that may be complicated by pyogenic bacteria or other fungal species.7 What About Using A Shampoo As A Preventive Foot Wash? One novel approach for treating tinea pedis and other fungal and bacterial infections is using ciclopirox in the shampoo formula as a foot wash to curb infection and using it prophylactically as well to prevent recurrence. I have used the shampoo as a foot wash in a clinical setting, both as part of a treatment regimen and prophylactically. Although there are no good studies to prove the specific effectiveness of Loprox® (ciclopirox) Shampoo as a foot wash, some authors have concluded that ciclopirox in the shampoo formula makes an effective foot wash if it is used daily, and it appears to decrease the chance of relapse and reinfection after one treats tinea pedis topically.14 Anecdotally, I have found that foot infections resulting from fungal and bacterial pathogens can be effectively controlled with ciclopirox shampoo. The process involves having the patient put a small amount of the shampoo on both feet and washing the lower leg and foot completely. Patients may do this at the beginning of a shower or at the end. They should rub in the shampoo with a small amount of water, leave the shampoo lather on for a few minutes and then rinse it off. There are alternatives for patients who may have difficulty reaching their feet in the shower. One option is to use a soft-bristled back brush with a small amount of shampoo to wash both feet. Another option is to telling the patient to sit in an empty tub, wet his or her feet and then wash them with the shampoo as described. After a few minutes, the patient can rinse off the shampoo and dry his or her feet before leaving the tub. Patients should repeat this process daily in order to prevent the recurrence of bacterial and fungal foot infections. Recommendations for reducing the incidence of reinfection by fungal or bacterial pathogens include: bathing daily and drying feet well between the toes; wearing socks that absorb moisture and wick it away from the skin; changing shoes daily; wearing sandals or shoes that allow air to circulate; and using antifungal and antibacterial agents to prevent recurrence.15,16 According to Gupta, et. al., ciclopirox offers advantages in treating tinea pedis with its antifungal, antibacterial, and antiinflammatory properties.10,11 In a double-blind, randomized, vehicle controlled study by Aly et. al., they found daily use of ciclopirox gel for four weeks effective and safe for treating moderate to severe tinea pedis interdigitalis.17 Ciclopirox in gel formula is indicated for the treatment of interdigital tinea pedis as well as seborrheic dermatitis of the scalp and tinea corporis.18 In addition to addressing issues of chronic nail trauma and avoiding irritants associated with paronychia and onycholysis, eliminating possible exacerbating pathogenic fungi with a broad-spectrum antifungal agent has been associated with positive treatment outcomes.19 Taking A Closer Look At Ciclopirox And Its Mechanism Of Action Ciclopirox (Loprox) is currently indicated for topical treatment of a broad range of dermal fungal infections including: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum, and Microsporum canis. It is also indicated for candidiasis due to Candida albicans and tinea versicolor due to Malassezia furfur.18 Ciclopirox also has in vitro activity against many gram positive and gram negative bacteria including Proteus species, Pseudomonas species, Proprionibacteria acnes, and Cornybacterium minutissimum.20 Researchers have also shown that ciclopirox may exhibit better antiinflammatory activity than 2.5% hydrocortisone.21 Ciclopirox is a synthetic, broad-spectrum hydroxypyridone antifungal, antibacterial and antiinflammatory agent that differs chemically and mechanistically from other antifungal drugs in the azoles and allylamine classes.21-24 Ciclopirox kills fungi via chelation of polyvalent cations and inhibition of metal dependent enzymes, including those responsible for degradation of peroxides.22-24 Other antimycotics only alter steps in the sterol biosynthesis of fungal membrane. Ciclopirox primarily affects iron-dependent enzyme systems such as cytochromes, catalase and peroxidase. It also impairs the activity on mitochondrial hemoproteins by binding with iron, thus killing the cell organism. Ciclopirox affects the cytoplasmic membrane as well as it appears to impair active transport mechanisms, cell respiratory processes and membrane integrity. It also negatively influences the macromolecular synthesis of nucleic acids and proteins.21-24 Ciclopirox’s antifungal, antibacterial and antiinflammatory effects suggest a strong proclivity for daily prophylaxis use by patients susceptible to fungal and bacterial infections that can lead to decreased significant lower extremity problems. Using the shampoo as a foot and lower leg wash has several advantages including the fact that it is an ideal topical broad-spectrum agent, which is very efficacious in low concentrations. It is both keratinophilic and lipophilic, allowing for better penetration and fungicidal activity. There is a reservoir effect in the stratum corneum, resulting in high mycologic and clinical cure rates, a lack of microbial resistance, a very low relapse rate and a low overall incidence of adverse effects.25 Clinically, ciclopirox demonstrates powerful antifungal activity.21,24 Researchers have shown that a 1% preparation of ciclopirox penetrates all layers of the stratum corneum of human skin and inhibits the growth of Trichophyton mentagrophytes. It also has proven in vitro fungicidal activity against Trichophyton rubrum, Epidermophyton floccosum, Candida albicans, and Microsporum canis.26 In Conclusion Therefore, it is reasonable to propose that ciclopirox’s antifungal, anti-inflammatory and antibacterial properties can reduce the number of foot infections by inhibiting potential pathogen colonization and reducing the likelihood of their recurrence in patients with diabetes. As the number of people who constitute “at-risk” population increases, fungal and bacterial skin infections will rapidly increase and impact the pharmacoeconomic concern of health care.31 Early recognition and treatment of lower extremity problems will help prevent direct morbidity and other complications. Given its antifungal, antibacterial and antiinflammatory properties, ciclopirox shampoo may be used as an ancillary therapy to control pathogens and help promote rapid healing.15,19,22,27 Using the shampoo formulation of ciclopirox as a specific foot wash treatment regimen and prophylacticaly could have a significant impact on reducing morbidity in specific populations and reducing complications. Dr. Dockery is a Fellow of the American Society of Podiatric Dermatology and the American College of Foot and Ankle Surgeons. He is the Founder and Director of Scientific Affairs of the Northwest Podiatric Foundation Education and Research, USA in Seattle. Dr. Steinberg (pictured) is an Assistant Professor in the Department of Orthopaedics/Podiatry Service at the University of Texas Health Science Center.
References 1. American Diabetes Association: Diabetes Facts: The Dangerous Toll of Diabetes. Alexandria, Virginia. 1996. 2. Reiber GE, Boyko EJ, Smith DG: Lower extremity foot ulcers and amputations in diabetes. Diabetes in America, 2nd Edition. Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, eds. U.S. Government Printing Office. Washington, DC,1995:409-428. 3. Armstrong DG: Is diabetic foot care efficacious or cost effective? Ostomy Wound Manage. 2001;47(4):28-32. 4. Grunfeld C: Diabetic foot ulcers: etiology, treatment, and prevention. Adv Intern Med. 1991;37:103-132. 5. Pecoraro RE, Reiber GE, Burgess EM: Pathways to diabetic limb amputations: basis for prevention. Diabetes Care. 1990;13(5):513-521. 6. Dockery GL: Fungal, Skin and Nail Infections. Cutaneous Disorders of the Lower Extremity. WB Saunders Co., 1997: (Chapter 6)52-65. 7. Aye M. Masson EA: Dermatological care of the diabetic foot. Am J Clin Dermatol. 2002;3(7):463-74. 8. Odom R: Pathophysiology of dermatophyte infections. J Am Acad Dermatol. 1993;28(5 pt 1):S2-7. 9. Masri-Fridling GD: Dermatophytosis of the feet. Dermatol Clin. 1996;14(1):33-40. 10. Gupta AK, Skinner AR, Cooper EA: Interdigital tinea pedis (dermatophytosis simplex and complex) and treatment with ciclopirox 0.77% gel. Int J Dermatol. 2003;42 (Suppl):23-27. 11. Gupta AK, Chow M, Daniel CR, Aly R: Treatments of tinea pedis. Dermatol Clin. 2003;21(3):431-62. 12. Daniel CR: Nails. Common Problems in Dermatology. Greer KE, ed. Year Book Medical Publishing. Chicago, Ill.1988:249-255. 13. Daniel CR: Onycholysis: an overview. Semin Dermatol. 1991;10(1):34-40. 14. Bell FE, Daniel CR, Daniel MP: Ciclopirox olamine: head to foot. J Drugs Dermatol. 2003;2(1):50-51. 15. Ramsey ML: Athlete’s foot: clinical update. Physician Sports Med. 1989;17:83. 16. Davis DM, Garcia RL, Riordon JP, Taplin D: Dermatophytes in military recruits. Arch Dermatol. 1972;105(4):558-60. 17. Aly R, Fisher G, Katz HI, et al: Ciclopirox gel in the treatment of patients with interdigital tinea pedis. Int J Dermatol. 2003;42(Suppl):29-35. 18. Gupta AK: Ciclopirox gel: an update. Int J Dermatol. 2003;42(Suppl):1-2. 19. Daniel CR, Daniel MP, Daniel CM, Sullivan S, Ellis G: Chronic paronychia and onycholysis: a thirteen-year experience. Cutis. 1996;58(6):397-401. 20. Gupta AK: The spectrum of utility of ciclopirox for the treatment of superficial fungal and bacterial infection. Ann Dermatol Venereol. 2002;129:IS607-IS842. 21. Rosen T, Schell BJ, Orengo I: Anti-inflammatory activity of antifungal preparations. Int J Dermatol. 1997;36(10):788-92. 22. Markus A: Hydroxy-pyridones: Outstanding biological properties. Hydroxy-pyridones as Antifungal Agents with Special Emphasis on Onychomycosis. Shuster S, ed. Springer. New York. 1999:Chapter 1. 23. Lassus A, Nolting KS, Savopoulos C: Comparison of ciclopirox olamine 1% cream with ciclopirox 1%-hydrocortisone acetate 1% cream in the treatment of inflamed superficial mycoses. Clin Ther. 1988;10(5):594-599. 24. Abrams BB, Hanel H, Hoehler T: Ciclopirox olamine: a hydroxypyridone antifungal agent. Clin Dermatol. 1992;9:471-477. 25. Gupta AK, Daniel CR: Onychomycosis: strategies to reduce failure and recurrence. Cutis. 1998;62(4):189-191. 26. Aly R, et al: Ciclopirox olamine lotion 1%: bioequivalence to ciclopirox olamine cream 1% and clinical efficacy in tinea pedis. Clin Ther. 1989;11(3):290-303. 27. Gupta AK: Types of onychomycosis. Cutis. 2001;68(2 Suppl):4-7.