How should metronidazole be used for chronic wound odor?

Introduction
Approximately 2.5% of the United States population is affected by chronic wounds which can have a significant impact on quality of life due to the need for frequent dressing changes and complications such as pain, infection, and odor.1,2 Fungating wounds, a type of chronic wound resulting from tumors under the skin, can be especially malodorous and distressing to the patient.

Odor control of chronic wounds is often attempted with mechanical debridement, topical antibiotics (due to the known contribution of anaerobic organisms), odor-absorbing dressings, and/or soaks with dilute acetic acid, hypochlorous acid, or Dakin solution.3,4 Although there are several potential treatment options for odor control in patients with chronic wounds, metronidazole is a long-standing treatment option. Literature supporting the use of metronidazole for controlling odor in chronic wounds dates to the 1960s; however, questions remain regarding the efficacy, optimal dose, and administration.

Guideline recommendations
The 2023 update of the Wound Healing Society guidelines for pressure ulcers include recommendations for odor control.5 They recommend use of topical metronidazole and/or antiseptics, or charcoal/activated charcoal based on low-level evidence due to a lack of well-designed clinical trials. The guidelines consider metronidazole formulations including gel, cream, or tablets to have equal efficacy.

Literature review
Systematic reviews
Several systematic reviews have evaluated metronidazole for odor control in a variety of wound types.2,6-8 A 2023 systematic review identified 4 clinical trials evaluating metronidazole and 1 trial evaluating silver for odor control in chronic or malignant fungating wounds.2 All included metronidazole studies had small sample sizes (N=11 to 41) and were of short duration (7 or 8 days). No meta-analysis could be conducted due to large variability in interventions, study design, and treatment. All studies from the systematic review are summarized in the Table.9-12 Only Bale et al (2004; N=41) included patients with venous, arterial, pressure, or other wound types while the remaining studies were limited to malignant fungating wounds. Other, older systematic reviews for odor control in chronic wounds did not identify any additional clinical trials for metronidazole.6-8

Clinical trials and case reports
Randomized controlled trials (RCTs), observational studies, and case reports have evaluated various metronidazole regimens for chronic or malignant fungating wound odor; however, there are few adequately powered, well-designed randomized controlled trials.9-19 Summaries of studies or case series describing clinical outcomes with topical metronidazole are summarized in the Table.

Table. Metronidazole for odor control in patients with chronic wounds.9-19 
CitationStudy design SubjectsInterventionsKey clinical outcomes
Clinical Trials
Al-arjeh et al (2020)13SC, single-arm trialN=15 patients with cancer and nonsurgical malodorous wounds up to 225 cm2Metronidazole 500 mg crushed tabletsMean odor scores on a 0 to 10 scale were significantly reduced in the first 24 hours as rated by nurses (7.2 on day 1 to 4.6 on day 2) and patients (7 on day 1 and 4.4 on day 2)

By day 5, mean odor scores decreased 5.9 points per nurse report and 6.1 points per patient report
Peng and Dai (2020)14SC, RCTN=73 patients with fungating wounds up to 25 x 20 cmMetronidazole powder with debridement gel (n=36)

Sulfadiazine silver ion dressing with debridement gel (n=37)

Dressings were changed as needed		Odor control on day 12 was improved to a greater extent with metronidazole than sulfadiazine silver with only1 serious malodor versus 6 in the sulfadiazine silver group
Villela-Castro et al (2018)9SC, DB, RCTN=24 patients with fungating woundsMetronidazole 0.8% topical solution (n=12)

Polyhexanide (PHMB) 0.2% solution (n=12)

With dressing changes at least twice daily		A total of 83.3% of patients had no odor at 4 days and 100% were odor free by day 9

No difference between groups
Watanabe et al (2016)15MC, single-arm trialN=21 patients with breast cancer and fungating woundsMetronidazole 0.75% gel applied once or twice daily up to a maximum daily dose of 30 g for 14 daysOn day 14, 95.2% of patients had an odor score of 0 or 1 (on a 5-point scale)

71.4% of patients reported satisfaction with metronidazole gel
Lian et al (2014)10SC, RCTN=30 patients with cancer and fungating woundsMetronidazole powder (n=15) from crushed tablets at a dose of 400 mg per 50 cm2 wound size

Green tea (n=15) irrigation solution followed by dry green tea bag inserted after irrigation

Both interventions applied daily with dressing change		Median odor scores on a 0 to 10 scale were similar between groups at baseline with patient ratings of 6 and nurse ratings of 5

Both groups had decreases in odor scores by day 7 with a median of 0 in the metronidazole group and 1 in the green tea group by both patient and nurse ratings
Bale et al (2004)11DB, PC, RCTN=41 patients with malodorous wounds (scoring at least 6 on a 10-point scale of 1-10)Metronidazole gel (n=20)

Placebo gel (n=21)

Daily with dressing changes for a duration of 7 days		Baseline median odor scores ranged from 6 to 8 in both groups

By day 7, median odor scores reported in the metronidazole group by the patient, study nurse, and caregiver were 1, 1, and 1, respectively which were similar to median odor scores in the placebo group (1, 1, and 2)
Finlay et al (1996)12MC, single-arm trialN=47 patients with foul smelling cutaneous lesionsMetronidazole gel 0.75% applied to silicone dressing after daily cleaning with normal salineAt baseline, 64% of patients had smell scores of mild, moderate, or extremely offensive which decreased to 11% by day 7 and 4% by day 14

25 patients had anaerobic colonization at baseline, but by day 14 only 1 patient had anaerobic organisms
Bower et al (1992)16DB, PC, RCTN=11 patients with fungating wounds and an odor score of at least 6 on a 0- to 10-point scaleMetronidazole gel 0.8% 1 g/cm2 (doses varied from 3.75 to 15 g per day depending on lesion size)

Placebo gel

Administered for 6 days followed by 5 days of open-label treatment of active metronidazole gel		Through day 6, patients in the placebo group maintained an odor score above 6 by both patient and medical staff observation while the metronidazole group decreased from 7.8 on day 0 to 5.0 on day 6 as graded by the patient and from 6.5 to 4.3 as graded by the medical staff

At the end of the open-label period, all patients had improvement in odor and no patients reported adverse events
Case reports/series
Harano et al (2024)17Case reportN=1 patient with gingival cancerMetronidazole spray (500 mg/100 mL) solution to the oral cavity after every meal (estimated dose of 2.4 to 3.2 mg per dose)Baseline odor on a 0 to 10 scale was 7 which was reduced to 1 after 7 days of treatment

Odor control was maintained through discharge
Hu et al (2019)18Case reportN=2 patients with cancer and fungating tumorsCase 1: A single 500 mg metronidazole tablet crushed and sprinkled into the 2 largest (about 35 cm2) tumors twice daily

Case 2: A single 500 mg metronidazole tablet crushed and sprinkled into the tumors twice daily		Case 1: Patient reported complete odor improvement after 24 hours; however, after discharge 1% metronidazole gel was ineffective for odor control

Case 2: Immediate reduction in malodor and reduced tumor exudate after several days
Kuge et al (1996)19Case seriesN=5 patients with breast cancer and fungating woundsMetronidazole gel 0.8%Odor disappearance was reported in 4 patients in a median of 4 days after metronidazole treatment; 1 patient died prior to odor disappearance on day 7 of treatment
Abbreviations: DB=double-blind; MC=multicenter; PC=placebo-controlled; RCT=randomized controlled trial; SC=single-center.

Conclusion
The evidence base for topical metronidazole includes a range of study designs from case reports to RCTs. Studies are limited by small sample sizes, largely single-center designs, and lack of a control group or controlled with unestablished therapy. Most studies lack full details regarding dressings, irrigation, and metronidazole application. Metronidazole administration was heterogenous with most of the evidence for metronidazole gel. However, the use of crushed tablets has been studied and recently use of a metronidazole spray was reported. In some reports, the frequency of metronidazole administration was unclear; when reported, it was commonly administered once or twice daily.

Despite the varied and limited literature, metronidazole gel and powder from crushed tablets appear to be effective for malodorous wounds likely due to its anaerobic properties. Currently. there is no consensus on the preferred dose or dosage form.

References

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  3. Evans K, Kim PJ. Overview of treatment of chronic wounds. UpToDate. Updated November 8, 2024. Accessed March 6, 2025. https://www-uptodate-com.proxy.cc.uic.edu/contents/overview-of-treatment-of-chronic-wounds?search=chronic%20wound&source=search_result&selectedTitle=1%7E150&usage_type=default&display_rank=1#H3325763073
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  9. Villela-Castro DL, Santos VLCG, Woo K. Polyhexanide Versus Metronidazole for Odor Management in Malignant (Fungating) Wounds: A Double-Blinded, Randomized, Clinical Trial. J Wound Ostomy Continence Nurs. 2018;45(5):413-418. doi:10.1097/WON.0000000000000460
  10. Lian SB, Xu Y, Goh SL, Aw FC. Comparing the effectiveness of green tea versus topical metronidazole powder in malodorous control of fungating malignant wounds in a controlled randomised study. Proc Singapore Healthcare. 2014;23(1):3-12. https://doi.org/10.1177/201010581402300102
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Prepared by:
Courtney Krueger, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

April 2025

The information presented is current as March 10, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.