DO NOT DUPLICATE. Topical Metronidazole for the Treatment of Wound Odor:

CE Article Topical Metronidazole for the Treatment of Wound Odor: A Review of the Literature Julia C. Paul, MSN, CCRN, CS, NP, CWS, RN; and Barbara A. Pieper, PhD, APRN, BC, CWOCN, FAAN CE information Topical Metronidazole for the Treatment of Wound Odor: A Review of the Literature Release date: March 1, 2008 Expiration date: February 28, 2009 Learning Objectives: Upon completion of this educational activity, participants should be able to: Discuss the impact of wound odor on patients quality of life Describe positive effects of topical metronidazole on wounds Credits: Nurses: 1 Contact Hour(s) Method of Participation: Read the article, complete the post-activity test and evaluation, and submit to: North American Center for CME 83 General Warren Blvd. #100 Malvern, PA 19355 Fax: (610) 560-0501 Successful Completion: Successful completion entails participants obtaining a score of at least 70% on the post-test. A certificate of completion will be mailed to the address listed on the participant s post-test/evaluation form within 6 weeks of receipt of the documents. Nurses: ANCC: North American Center for Continuing Medical Education is an approved provider of continuing nursing education by the Pennsylvania State Nurses Association, an accredited approver by the American Nurses Credentialing Center s Commission on Accreditation. This continuing nursing education activity was approved by the PA State Ms. Paul is a Doctoral Student and Dr. Pieper is a Professor/Nurse Practitioner, Wayne State University, College of Nursing, Detroit, Mich. Please address correspondence to: Julia C. Paul, MSN, CCRN, CS, NP, CWS, RN, College of Nursing, Wayne State University, 5557 Cass Avenue, Detroit, MI 48202; email: juliapaul@wayne.edu. 18 OstomyWound Management Nurses Association for 1 contact hour(s). Provider #: 110-3-E-03. Provider approved by the California Board of Registered Nursing, Provider Number 13255 for 1 contact hour(s). Faculty Disclosures: All faculty participating in Continuing Education programs sponsored by the North American Center for Continuing Medical Education are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation. It is not assumed that these financial interests or affiliations will have an adverse impact on faculty presentations; they are simply noted here to fully inform participants. Dr. Pieper has disclosed that she has received grant/research support from NIH/HINR. Editor: Ms. Zeiger has disclosed that she has no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the context of the subject of this article. All NACCME employees involved in the planning and editing of this educational activity have disclosed that they have no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the context of this educational activity. Off-Label/Unapproved Usage Discussion: This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither NACCME nor the manufacturers of products mentioned in this article recommends the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Sponsor: North American Center for Continuing Medical Education

Unpleasant odor is a frequent and distressing concern of persons who have wounds, as well as their family members and caregivers. In some instances, standard nursing interventions such as increasing the frequency of dressing changes will not be sufficient to address wound malodor. A review of the literature to summarize research findings about topical metronidazole used to decrease wound odor was conducted. Fifteen (15) studies were identified: seven case reports/series; six descriptive longitudinal studies; and two controlled clinical trials. Metronidazole was used as a 1% solution or, more frequently, as a 0.75% or 0.80% gel. Two reported adverse effects were skin irritation and a burning sensation. Generally, topical metronidazole was reported to result in a reduction or eradication of wound odor, decrease in wound drainage, improvement in wound appearance, decrease in surrounding cellulitis, halting of tissue necrosis, and decrease in pain. Although nurses report success with sprinkling crushed metronidazole pills on wounds, no published reports of this method of topical application are available. Topical metronidazole may be considered as an option for the management of malodorous wounds and additional randomized controlled trials with adequate sample sizes and comparison to products noted to decrease odor are warranted. While topical metronidazole for the treatment of malodorous wounds presently is off-label, perhaps such studies will result in the addition of malodorous wounds to the list of its indications. KEYWORDS: wound odor, metronidazole Ostomy Wound Management 2008;54(3):18 27 Western society promotes pleasant fragrances. application of metronidazole. Because topical metronidazole for wound odor is generally not presented in Cleaning products, soaps, perfumes, deodorants, and the like are formulated to evoke pharmacology books and clinicians often are asked to positive thoughts and feelings. In contrast, unpleasant odors are distressing. Consciously or unconsciously, unpleasant odors cause avoidance, a primordial, protective provide evidence-based research for a treatment, a search of the literature was conducted of PubMed and CINAHL using terms including metronidazole, Flagyl reaction to potentially dangerous substances. (G.D. Searle, LLC, Chicago, Ill), MetroGel (Galderma Unfortunately, wounds often have an unpleasant odor. Malodorous wounds are defined as those identified by patients, family or practitioners as having an offensive smell 1 ; malodor may be the most devastating aspect of having a wound. Odor is a constant reminder that something is wrong with the body and may be associated with infection, presence of necrotic material, devitalized tissue, Production Canada, Inc., Montreal), wound odor, and wound malodor. Restrictions were not placed regarding years of inclusion. References at the end of published papers about wound odor also were searched. Research relevant to the topical application of metronidazole to decrease wound odor summarized in this article includes papers/letters that reported case studies and patient- fungating malignant tumors, and poor wound care related research versus product descriptions. practices. Odor can permeate clothing, furniture, and living Examining research findings about a product can help quarters. The person who has wound odor may experience embarrassment; anxiety; fear; revulsion from family, friends, and healthcare Ostomy Wound Management 2008;54(3):18 27 providers; social isolation; depression; decreased KEY POINTS appetite; and nausea, typically at a time when the person needs supportive care the most. 2 4 In For some patients, wound odor is a constant and distressing companion. the last 6 months of life, 5% to 10% of persons The literature summarized here suggests that metronidazole may with metastatic disease develop skin involvement that can lead to wound odor. 5 Aside from help reduce wound odor and improve wound status. While additional research is needed, the authors suggest consideration of this treatment when the problem of wound odor cannot be treating its cause, wound odor may be alleviated by applying various dressings and substances to addressed using standard nursing care interventions. the wound. One such treatment is the topical March 2008 Vol. 54 Issue 3 19

the clinician select the best options for odor control. Although the focus of this paper is topical metronidazole, a summary of systemic metronidazole for wound odor also is presented. Wound Odor Malodorous wounds are generally polymicrobic, containing anaerobes and aerobes; the level and type of bacteria affect the wound environment. 6 Anaerobic bacteria that cause infection and generate odor include bacteroides such as Bacteroides fragiles, Prevotella, Fusobacterium nucleatum, Clostridium perfringens, and anaerobic cocci. 1,6 The anaerobes emit putrescine and cadaverine, two ulcer-linked smells. 6 People who are not accustomed to odor produced by putrescine or cadaverine tend to gag or vomit from the odor. 7 Aerobic bacteria also produce offensive odor and include species of Proteus, Pseudomonas, and Klebsiella. 6 Cutting and Harding 8 suggested that abnormal wound smell should be considered a criterion for identifying wound infection. Devitalized tissue, strike-through drainage, inappropriate dressing selection, dressings left on too long, and general poor hygiene are other causes of wound odor. 6 Odor assessment is subjective. Molecules of various odors are breathed into the nose; they reach and match the olfactory receptors that register the smell as ranging from pleasant to unpleasant. 1,9 Wound odor may be so foul that it leads to repulsive movements and uncontrollable reaction by others. 9 Descriptive terminology for wound odor is important because wound odor is likely to change over time. Baker and Haig 10 presented a subjective assessment tool for scoring wound odor: strong odor noted in room even when dressings are in situ (score 4), moderate odor detected at six feet with the dressing removed (score 3); faint odor detected only at close range with dressing removed (score 2); no odor even at close range (score 1). Others have used 10- or 11- point visual analogue scales ranging from 0 or 1 (no/slight odor) to 10 (worst odor). 1,11,12 Patient and Wound Considerations Assessment. If wound odor is present, the patient s overall health status and the wound need to be assessed. The assessment should include the person s comorbid health problems, medications, nutritional status, and diagnostic test findings as well as psychosocial implications. Wound assessment should follow a typical protocol that addresses wound location, size, depth, undermining, edema, tunneling, pain, necrotic tissue, granulation tissue, and epithelialization. The cause of the wound is critical because odor has been associated with typical wounds such as pressure ulcers and lower extremity ulcers as well as malignant tumors (ie, fungating wounds). 13 If necrotic tissue is causing the odor, debridement by a method appropriate for the patient s overall health status and wound should be considered. Routine cultures of clinically uninfected chronic wounds are not recommended. 14 Systemic antibiotics may be used to eradicate the infection. The wound care protocol should be evaluated. For example, wound cleansing is a process that removes loose bacteria and foreign material from the wound surface; the pressure needed for wound cleansing has been found to vary from 5 psi to 15 psi. 15 Dressings should be evaluated in terms of ability to contain drainage and the frequency of change. If the dressing is inappropriate or the patient or family is not providing adequate wound care, the reason(s) for inappropriate/inadequate care needs to be identified and corrected. Problems in this area may be related to the cost of dressing supplies, the unavailability of sufficient dressing supplies, the lack of assistance in the home, or the fear of changing a dressing. Leakage of wound drainage from under the dressing may be a problem; protocols regarding dressing supplies and dressing change frequency need to be developed to prevent this leakage from occurring. Because malodor is sensed by olfactory receptors in the recess behind the nose, at a conscious and subconscious level, odor can affect taste and flavor; thus, appetite may be reduced. 16 In addition to the impact of the wound odor on the patient s quality of life, caregiver/family concerns also must be addressed. Patients at the end of life or persons living in shelters or group homes/settings may have unique needs. Wilkes et al 17 examined palliative care nurses (N = 26) experiences caring for patients with malignant malodorous wounds. Nurses were challenged to lessen the impact of the wounds, obtain the right products, and consider costs for the family. Using qualitative analysis, two themes were identified describing the nurses experiences: supporting 20 OstomyWound Management

Author/Year Jones, Willis, Ferguson/ 1978 20 Gomolin, Brandt/1983 25 Pierleoni/ 1984 26 Allwood, Henderson, Hunt/ 1986 27 Burnakis/ 1989 37 Sample Size None stated N = 4; ages 83 88 years; three men and one woman N = 2; ages 76 and 85 years More than 50 patients over a 2- year period (specific number not stated). Age and sex of patients not stated N = 1; age not stated. Continued use with 15 to 20 patients TABLE 1 TOPICAL METRONIDAZOLE FOR WOUND ODOR: SUMMARY OF PUBLICATIONS Metronidazole Dose/Route 1% solution in 0.6% saline; sterilized by autoclaving at 121 C for 20 minutes Crushed metronidazole tablet or powder for laboratory use mixed with sterile water for a 1% solution Crushed metronidazole tablet in sterile water as a 1% solution Gel (% not stated). Supplemented with metronidazole irrigation Prepared 1% solution from crushed oral tablets in normal saline; autoclaved mixture 121 C for 20 minutes. Revised: two vials each 500 mg/5 ml in 100 ml normal saline Topical 0.8% gel Type of Study Letter to editor; case report Case report Case report Letter to editor; case report Case report; no description of patient Protocol Apply as a wet dressing Solution applied to sterile gauze; dressing packed; changed every 8 hours Solution applied to sterile gauze; dressing changed every 8 hours Wound irrigated with metronidazole; gel applied and covered with dressing; changed one time per day Solution applied once per shift on 4 cm x 4 cm sterile gauze. Revised: 10 ml solution to 4x4; packed into wound; allowed to dry; removed; heat lamp applied 20 to 30 minutes Wound Type Pressure ulcers, diabetic foot ulcers, venous ulcers, abscesses Pressure ulcers; Stage II to Stage IV Pressure ulcers; Stage III and Stage IV Wound type not stated; all patients at a terminal care center Pressure ulcer (stage and description not given) Results No statistics. Odor no longer present within few hours. Within 24 hours, ulcers were clean and free of anaerobes and surrounding marginal cellulitis was resolving No statistics. Some wound descriptions given. Odor and drainage decreased in 2 to 7 days and granulation tissue appeared. Percutaneous absorption not measured but estimated in a large ulcer to be no more than 300 mg daily. The authors did not believe the effectiveness was due to increased nursing attention because all wounds received similar nursing care prior to the treatment No statistics. Highly effective in controlling drainage and odor and clearing surrounding cellulitis No statistics. Odor decreased No statistics. Odor disappeared in 24 to 48 hours. Ulcer progression stabilized. Necrosis was halted. Granulation tissue beginning at edges March 2008 Vol. 54 Issue 3 21

Odor completely controlled in 34 lesions (50%), reasonable odor reduction in 31 lesions (46%), and ineffective for three. Gel effective in a majority of wounds in 2 days, but ranged from 1 to 30 days. One adverse event of skin irritation after 7-day treatment of infected leg ulcer. No control group; the impact of controlling exudate and the wound care protocol are not known 32 patients breast cancer; 24 patients other cancers; 12 patients pressure ulcers and other lesions Gel applied to the lesions. Medical staff assessed effectiveness as completely successful, reasonably effective, or ineffective Descriptive longitudinal. Variable follow up: 4 days to 15 months. Multicenter, nonrandomized trial N = 68 (age not stated) Newman, Allwood, Oakes/1989 28 26 isolates were cultured before treatment. Cultures negative for anaerobes in 5 days for Sacral pressure ulcers Stage III and Stage IV Irrigated with normal saline, thin layer of gel applied to wound base, walls, and under overhanging margins of the ulcer. This was packed with fluff gauze and covered with abdominal dressing pad. Treatment repeated every 12 hours Descriptive, longitudinal. Followed 5 days Topical gel (% not stated) N = 10; mean age 79 years. All patients had serious acute and chronic illnesses. Ulcers were cultured. Necrotic debris superficially debrided Witkowski, Parish/1991 29 metronidazole. Odor eliminated in all wounds in 36 hours. Decreased drainage; tissue necrosis stopped; granulation present. Concluded the metronidazole must come in contact with entire wound surface Within 24 hours, no odor except at close range. Odor completely eliminated in 5 days. Pain decreased; wound appearance improved. No adverse events Four patients with cancer lesions; Two patients with radiation necrosis; two with fistulas; three with pressure ulcers Gel applied to the wound and covered with telfa; dressing changes one to two times per day. Fistulas were irrigated with solution Descriptive longitudinal; followed 7 days Topical 0.75% gel for wounds or 1% solution for fistula irrigation N = 11; ages 31 to 86 years; seven men, four women McMullen/ 1992 30 and maintaining the patient as a person considering the horrific nature of the wound and the personal challenge to care. Continuity of holistic care is paramount. Treatment. After the person and the wound are assessed, appropriate treatment for the odor can be determined. Silver preparations or cadexomer iodine wound products may decrease the bacterial burden or infection in a wound. Activated charcoal dressings filter wound odor. Oral and/or topical metronidazole may be considered. Some patients may desire alternative therapies such as sugar, honey, and plain yogurt with live cultures to control odor. 4,9,18,19 Room deodorizers and linen and clothing changes may be helpful. Deodorants, incense, chemical wicks, scented flowers and plants, and perfume only mask the odor and may cause an aversion to the product in the future. Thus, more than one treatment strategy usually is involved in the plan to eradicate or decrease wound odor. Metronidazole Metronidazole (Flagyl, G.D. Searle, LLC, Chicago, Ill) is in the pharmacologic drug class nitroimidazole and the therapeutic classes antibacterial, antiprotozoal, and amebicide. It is listed as a 22 OstomyWound Management

Odor scores improved (not statistically significant) in the treatment group (patients odor scores decrease from7.8 to 5; medical staff, 6.5 to 4.3). Phase 2: placebo group significantly decreased odor (patient 6.8 to 1.2; medical staff, 6.6 to 1.1); treatment group continued to improve. No adverse events or side effects. Some improvement in placebo group probably related to daily cleansing and dressing of wound. Recommended daily cleansing and dressing for 7 days followed by metronidazole for 5 days All had fungating tumors Daily cleansing and dressing. Metronidazole applied 3.75 to 15 g/day. Smell assessment limited to the researcher and patient on 0 to 10 visual analogue scale Double-blind, placebo-controlled trial. Two phases: Phase 1 days 0 to 7 and Phase 2 days 7 to 11 (all received metronidazole). Treatment group received metronidazole entire time. Control group received metronidazole in Phase 2. Topical 0.8% gel N = 11; 10 women, one man; Mean age = 68 years. Could not be receiving systemic antibiotic or antitumor therapy during the trial. Two patients withdrew for chemotherapy or antibiotics. Five were in placebo group and four in treatment group Bower, Stein, Evans, Hedley, Pert, Coombes/ 1992 11 No statistics; odor decreased subjectively after day 1. Eight patients showed clinical improvement in terms of decreased pain, decreased drainage, and increased granulation tissue Five fungating malignant tumors,eight pressure ulcers Stage III and Stage IV Gel applied to wound and covered with moist normal saline or Cara Klenz (Carrington Laboratories, Tex) one time per day Descriptive longitudinal; followed 9 days. Used Baker and Haig odor assessment tool Topical 0.75% gel N = 13; age range 44 to 94 years Poteete/1993 31 No statistics Odor disappeared, necrotic tissue removed, and healthy granulation tissue present within 48 hours of using metronidazole. Recommend 5- day course of metronidazole 0.8% gel applied daily. Arterial insufficiency of the left foot and necrotic ulcers Wet-to-dry dressing change two times per day. Also receiving whirlpool therapy and intravenous antibiotic ciprofloxacin two times per day Case study; followed for 19 days (5 days in hospital and 2 weeks at home) Topical solution made with 2.5 g of metronidazole per L of 0.6% hypotonic saline solution N = one man Kaplan, Gibson/ 1995 35 Pregnancy Category B drug. It disrupts DNA and protein synthesis of susceptible organisms. With anaerobic bacteria, the nitro group of the drug is chemically reduced to ferredoxin, which is bactericidal by reacting with intracellular macromolecules. 20 The product may be administered using oral, intravenous, and/or topical routes. Oral metronidazole. Oral metronidazole is readily absorbed and widely distributed in most tissues and fluids; plasma peak levels are reached in 1 to 3 hours. It is partially metabolized by the liver and excreted in feces and urine. Common adverse drug reactions, which tend to be mild and transient, include anorexia, nausea, abdominal pain, dizziness, and headache. 20 A dry mouth and a metallic taste also may occur. Taking the drug with meals lessons the gastrointestinal irritation. March 2008 Vol. 54 Issue 3 23

Finlay, Bowszyc, Ramlau, Gwiezdzinski/ 1996 32 Kuge, Tokuda, Ohta, et al/1996 33 Bale, Tebble, Price/2004 1 N = 48 patients consented. Mean age = 61 years (range 25 to 93). 12 men and 36 women. One excluded (no odor); one withdrew due to burning sensation from gel on day 2; three did not complete study (one transferred; two died from advanced cancer) N = five women; median age 59 years N = 41; 26 women and 15 men. Inclusion: able to rate odor at >6 on 10-point scale. Patient, two study nurses, and relative/caregiver completed odor ratings Topical 0.75% gel They formulated 0.8% metronidazole gel Topical gel (% not given). Statement of dressing protocol not given Multicenter, longitudinal open study design, no control group. Four centers. Patients assessed three times entry, day 7, and day 14. Assessed wound smell (0 to 4 scale), pain, appearance (0 to 3 scale), and bacteriological profile Descriptive Prospective placebo-controlled, randomized double blinded Assessed four times: entry into study and days 1, 3, 7. 21 in placebo group; 20 in metronidazole group. Remained in study until resolution of odor or 7 days. Power stated as 90% Cleansed with normal saline. Silicone dressing smeared with 0.75% gel and covered with sterile gauze Dressing with gel spread on it and applied one to two times per day. Systemic antibiotics not allowed during study. Cultures done. Gel used 6 to 131 days, median 37 days Odor, leakage, pain, and sleep rated on 10-point scales. Semantic Differential Scale and State Trait Anxiety Inventory administered 20 patients with fungating malignancy lesions; 27 patients with leg ulcers without malignancy Breast cancer 22 venous leg ulcers; two arterial leg ulcers; five pressure ulcers; 12 other Smell scores decreased but not significantly. Significant decrease in cellulites, discharge scores, pain scores, organisms on anaerobic culture. No significant decrease in aerobic organisms. No difference in scores by lesion type. One patient withdrew (burning sensation). Two patients had slight bleeding during dressing change Four patients odor disappeared in median 4 days. Aerobes and facultative bacteria did not change; anaerobes disappeared or decreased. No adverse reactions Metronidazole group had faster odor reduction by day 1 and near complete odor resolution by day 3. Odor significantly decreased in both groups. Days 1 and 3 no significant difference between groups in sleep, pain, or leakage. By day 3, pain significantly decreased in metronidazole group. Nurses and patients symptom ratings were positive and significant. No difference in mood states of the two groups over time. No adverse events 24 OstomyWound Management

Fungating cancer Statistically significant decrease in odor in 24 hours (and days 7 and 14) complete elimination of odor in 10 patients; six had significant odor control. Decrease in wound exudates, but not statistically significant. No adverse events noted Nonadherent primary dressing changed one to two times per day with absorbent gauze secondary dressing Topical 0.75% gel Prospective, descriptive, longitudinal, single center, no control group; followed 14 days. Wound odor scored 0 to 10 N = 16 No debridement done. Excluded patients on systemic antibiotics or current chemotherapy or radiotherapy or with sensitivity Kalinski, Schnepf, Laboy, et al/2005 12 Infrequent adverse reactions include diarrhea, glossitis, rashes, leucopenia, peripheral neuropathy, and (the most serious) seizures. The maximum daily dose for adults is 4 g and may be reduced in patients with severe hepatic impairment. Alcoholic beverages should be avoided during therapy and for 48 hours after completing therapy. Metronidazole potentiates the effects of some drugs including barbiturates, warfarin, lithium, phenobarbital, phenytoin, cimetidine, and disulfiram; thus, a review of a patient s medications is important. Metronidazole tablets are available in doses ranging from 200 mg to 500 mg and an extended release tablet of 750 mg. Topical treatment. Metronidazole (MetroGel, Galderma Production Canada, Montreal) 0.75% or 1% gel is a topical treatment. The 1% topical gel was tested for safety and efficacy in patients with acne rosacea. 21 Safety studies using patch testing demonstrated no significant evidence of irritation, sensitization, phototoxicity, or photoallergy. 21 Patients are instructed to use metronidazole gel externally as directed for the prescribed condition, avoid contact with the eye, cleanse the affected area before applying, and report any adverse reactions. 21 Although topical metronidazole gel can be absorbed in sufficient amounts to produce systemic effects, no reports of human experiences with overdose have been noted. 21 Pharmacologic references do not present information about its topical use for wound odor. Use of Metronidazole for Wound Odor Ashford et al 22 reported they were the first to use oral metronidazole 200 mg three times per day to decrease odor for a patient with an offensive-smelling breast cancer lesion. Odor during dressing changes was present but markedly reduced. The authors continued their work with a double-blind, cross-over trial comparing oral metronidazole 200 mg three times per day for 14 days to placebo. 2 Nine persons were initially enrolled; six patients completed the trial. Odor was scored as absent, not offensive, offensive but tolerable, or offensive and intolerable. Odor and the presence of anaerobic isolates on culture were significantly less with the metronidazole treatment. Doll and Doll 23 published a letter about two patients with ulcerating breast cancer; the patients were given oral metronidazole 250 mg three times per day for 10 days with complete amelioration of their wound odor. Baker and Haig 10 examined the effects of oral metronidazole 400 mg three times per day among 53 pressure ulcer and venous ulcer patients on speed of healing, wound odor, pain, and wound appearance. Metronidazole was associated with a visible reduction in wound size but odor was not significantly affected. These studies of oral metronidazole lacked nursing care standardization (wound cleansing, care techniques), and solutions used. The PRODIGY guidance of the United Kingdom (part of the Clinical Knowledge Summaries of the National Library for Health) for palliative care recommends metronidazole use for wound odor ie, starting with oral metronidazole 400 mg three times per day and reducing the dose to 200 mg three times a day or 400 mg once per day if the person experiences nausea and vomiting. 24 Research findings are summarized in Table 1 and are limited to publications that could be accessed (not all articles could be located). Of the 15 articles analyzed, 10 had small sample sizes ranging from 1 to 16. March 2008 Vol. 54 Issue 3 25

Most studies were descriptive and/or case study reports the exceptions include Bower et al 11 (a double-blind, placebo-controlled study) and Bale et al 1 (a placebo-controlled, randomized, double-blinded study). Bower et al 11 recognized such obvious benefits with the use of topical metronidazole compared to a placebo they felt ethically obligated to give up randomization of the study and treat all participants with metronidazole. Statistical comparisons were generally not included in most reports of use of topical metronidazole and the majority lacked detailed descriptions of the wounds. Wound types most reported were pressure ulcers, fungating cancer lesions, venous ulcers, and arterial ulcers of the lower extremity. Wound care often was not presented in detail (ie, the amount of gel used, the amount of absorption of the gel into the dressing thus affecting availability to the wound, the impact of wound size and heavy exudates on effectiveness, and the amount of necrotic tissue). Trials comparing the oral and the gel administration have not been performed. Although nurses describe sprinkling crushed metronidazole pills on a wound, research regarding this practice was not found. Studies showed desirable results using either 0.75% gel or 0.80% gel. The gel was most frequently spread into the wound base and covered with saline-moistened or dry gauze dressing. Dressings using metronidazole as solution were typically applied every 8 hours 25,26 ; gel dressings were typically changed one to two times per day. 11,12,27-33 In one report, topical metronidazole treatment regimen was used for up to 15 months. 28 Bower et al 11 recommend daily wound cleansing and dressing changes for 7 days followed by a 5-day course of topical metronidazole. In contrast to the positive reports about topical metronidazole, Davies 34 published a case study in which topical metronidazole was rated ineffective for controlling odor. A 59-year-old woman suffered with a wound from adenocarcinoma of the descending colon and carcinomatosis; the wound was treated with 0.8% metronidazole gel covered with adhesive foam. When odor persisted, the dressing protocol was changed. The length of time of use was not presented. Kaplan and Gibson 35 note that topical metronidazole did not appear to be appreciably absorbed systemically. Gomolin and Brandt 25 estimated that large ulcers (approximately 10 cm x 10 cm) treated three times daily with 1% solution would receive about 300 mg metronidazole. Only two adverse effects of topical metronidazole were reported in the studies: skin irritation after 7 days of treatment of an infected leg ulcer 28 and a burning sensation on the second day of treatment. 32 Topical metronidazole had desirable results, including: decreased or eradicated wound odor, 1,11,12,26-33,35,36 decreased wound drainage, 25,26,29,31,32 improved wound appearance, 25,29-31 decreased surrounding cellulitis, 26,32 cessation of tissue necrosis, 29,35,37 and decreased pain. 29-32 Clinical Implications Topical metronidazole appears to be a safe and effective treatment for management of wound odor. Its use to treat wound odor needs to be considered in relation to the wound type, description, and other treatment options. It may be most effective where devitalized tissue cannot be penetrated by systemic therapy, as in cancerous lesions and fungating tumors. Although use of topical antibiotic solutions has been avoided because of the possibility of antibiotic resistance, treatment with topical as well as systemic metronidazole may reduce the possibility of antibiotic resistance. 4 Although systemic absorption of topical metronidazole has not been studied extensively, it does not appear to be a problem. However, clinicians should be cognizant of possible adverse effects that have occurred with systemic administration, including increased effects of oral anticoagulation, 13 alcohol intolerance, nausea, and neuropathy. 38.39 Some patients may not be candidates for the use of metronidazole because of hypersensitivity to the formulation. Some patients (approximately 2% according to Hampson 38 ) may experience skin irritation related to metronidazole; skin needs to be assessed for irritation and product use discontinued if it develops. Based on their findings from a longitudinal study of patients with malodorous cutaneous wounds, Finlay et al 32 estimated that the use of metronidazole gel is ten-fold the cost of metronidazole tablets; thus, product cost may be a deterrent to use. Additional research is needed regarding the topical use of metronidazole, especially crushed pills, because literature is lacking. Dressing protocols for topical metronidazole need to be re-examined and relevant options provided. Recommended length of therapy for topical metronidazole also needs further study. 26 OstomyWound Management

Systemic absorption from topical application should be determined and potential side effects considered. Use in children has yet to be studied. Conclusion Wound odor is distressing for the patient, family, and clinician. It is associated with infection, necrotic material, devitalized tissue, fungating malignant tumors, and poor wound care practices. Because odor can permeate clothing, furniture, and living quarters and interfere with quality of life, it must be controlled. Topical metronidazole has been shown to effectively manage odor associated with a variety of wounds. Case reports, longitudinal descriptive studies, and two randomized controlled studies support its use in controlling wound odor as well as cleaning the wound base. As with any treatment, topical metronidazole needs to be considered in relation to individual wound/patient characteristics and available dressings. The lack of data regarding use of crushed metronidazole pills applied topically for wound odor is regrettable because this approach has been shown to reduce the cost of topical metronidazole therapy. Additional studies to further elucidate optimal use of topical metronidazole are needed. - OWM References 1. Bale S, Tebbie N, Price P. A topical metronidazole gel used to treat malodorous wounds. Br J Nurs. 2004;13(11):S4-S11. 2. Ashford R, Plant G, Maher J, Teare L. Double-blind trial of metronidazole in malodorous ulcerating tumours. Lancet. 1984;1(8388):1232 1233. 3. Neal K. Treating fungating lesions. Nurs Times. 1991;87(23):84,86. 4. Benbow M. Malodorous wounds: how to improve quality of life. Community Nurse. 1999;5(1):43 46. 5. Haisfield-Wolfe ME, Rund C. Malignant cutaneous wounds: a management protocol. Ostomy Wound Manage. 1997;43(1):56 65. 6. Holloway S. Recognizing and treating the causes of chronic malodorous wounds. Professional Nurse. 2004;19(7):380 384. 7. Van-Toller S. 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