What is the evidence for safety and efficacy of metronidazole 0.75% gel for use in minimizing odor with a chronic wound?

What is the evidence for safety and efficacy of metronidazole 0.75% gel for use in minimizing odor with a chronic wound?

Comment by InpharmD Researcher

Data regarding the safety and efficacy of topical metronidazole gel for the management of wound malodor are limited and largely derived from small, dated studies. Available studies evaluating 0.75% to 0.8% metronidazole gel generally reported reductions in wound odor with few reported adverse effects. However, treatment duration, time to response, wound characteristics, and prior management strategies varied considerably across studies. Therefore, additional research is needed to determine the optimal role and treatment regimen of 0.75% metronidazole gel in this clinical setting.

Background

A 1998 article explored the efficacy of topical metronidazole gel as an antimicrobial agent for managing malodorous wounds. Wound odors caused by anaerobic bacterial activity are the result of volatile fatty acids produced during the breakdown of lipid by anaerobic bacteria present in devitalized and necrotic tissue. The wounds frequently associated with such malodour include fungating lesions, leg ulcers, pressure sores, and decubitus ulcers. Clinical research over the past two decades has consistently shown that topical application of metronidazole is effective against anaerobic infections, providing notable control of wound-related odors. The piece cites multiple studies, including a notable 1989 investigation by Newman et al. (Table 4), which treated 68 patients with malodorous wounds, achieving complete odor control in 34 patients and reasonable control in 31 others. While systemic metronidazole treatments may present side effects, the topical application in Metrotop has demonstrated minimal adverse reactions, making it a preferable option for patients and health professionals managing the complexities of malodorous wounds. [1]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What is the evidence for safety and efficacy of metronidazole 0.75% gel for use in minimizing odor with a chronic wound?

Level of evidence

D - Case reports or unreliable data Read more→

Please see Tables 1-4 for your response.

A topical metronidazole gel used to treat malodorous wounds
Design	Randomized, placebo-controlled double-blind study N= 41
Objective	To compare the efficacy of a metronidazole gel with a placebo in reducing the self-perception of odor for patients with malodorous wounds
Study Groups	Metronidazole gel (n= 20) Placebo (n= 21)
Inclusion Criteria	Patients with malodorous wounds who were able to rate the odor of their wound at more than 6 on a 10-point scale
Exclusion Criteria	Not specified
Methods	Patients were randomized to receive either topical metronidazole gel or placebo gel. The study gel was applied directly to the wound once daily with secondary dressings and appropriate bandaging. Wound odor was assessed using a 10-point scale at baseline and on days 1, 3, and 7, or until odor resolution, whichever occurred first. Patients could be withdrawn at day 3 if both the patient and nurse agreed there was no improvement in odor.
Duration	Treatment duration: 7 days
Outcome Measures	Resolution of odor
Baseline Characteristics		Metronidazole gel (n= 20)	Placebo (n= 21)
	Venous leg ulcer	12	10
	Arterial leg ulcer	2	0
	Pressure ulcer	1	4
	Other, e.g. surgical	5	7
	Mean length of wound duration, months	58.05	46.29
	Mean wound size (surface area), cm2	78.39	39.12
Results		Placebo (n= 21)	Metronidazole gel (n= 20)
	Patient odor score at Day 0	6.0	8.0
	Patient odor score at Day 1	5.0	3.5
	Patient odor score at Day 3	1.0	1.0
	Study nurse odour score at Day 0	7.0	7.5
	Study nurse odour score at Day 1	5.0	3.5
	Study nurse odour score at Day 3	2.0	1.0
	Odor scores decreased significantly in both groups according to patient, nurse, and caregiver assessments (p< 0.01). Patients receiving metronidazole reported more rapid odor improvement, with median odor scores decreasing from 8 at baseline to 3.5 on day 1 and 1 by day 3; patient-assessed odor reduction was significantly greater than placebo (p< 0.05). Nurse and caregiver odor ratings showed a similar pattern and correlated significantly with patient ratings. There were no significant differences between groups in sleep, leakage, mood (Semantic Differential Scale), or anxiety (State-Trait Anxiety Inventory) scores. Pain scores decreased significantly by day 3 in the metronidazole group according to patient (p< 0.001) and nurse (p< 0.01) assessments, with a significant between-group difference observed only for patient assessments (p< 0.05). By day 7, no significant differences between groups were observed, and 26 of 41 patients had completed the study early due to odor resolution.
Adverse Events	No adverse events reported
Study Author Conclusions	The study provides some evidence to support the use of metronidazole gel in the treatment of patients with malodorous wounds, but indicates the need for further research in this area.
Critique	The study was well-designed with a randomized, placebo-controlled double-blind approach. However, the unexpectedly high placebo effect and small sample size may have limited the ability to detect significant differences between groups. The subjective nature of odor assessment and the short follow-up period are additional limitations.

References:
[1] [1] Bale S, Tebbie N, Price P. A topical metronidazole gel used to treat malodorous wounds. Br J Nurs. 2004;13(11):S4-S11. doi:10.12968/bjon.2004.13.Sup2.13233

The Effect of Topical 0.75% Metronidazole Gel on Malodorous Cutaneous Ulcers
Design	Open, multicenter study N= 47
Objective	To assess the subjective and bacteriological response to 0.75% metronidazole gel in decreasing odor from malodorous cutaneous lesions and to evaluate bacterial contamination of gel tubes during use
Study Groups	All patients (N= 47)
Inclusion Criteria	Patients with benign or malignant cutaneous lesions associated with a foul smell, after simple cleansing and necessary debridement
Exclusion Criteria	Patients on systemic antibiotics, currently receiving radiotherapy or chemotherapy
Methods	Patients with malodorous cutaneous lesions received 0.75% metronidazole gel applied directly to the lesion once daily for 14 days. Lesions were cleansed with 0.9% sterile saline before application and covered with a nonadherent silicone dressing. Odor, lesion appearance, and pain were assessed on days 0, 7, and 14, and bacteriologic swabs were obtained at baseline and day 14. Odor was evaluated by the patient, nurse, and independent physician using a 0–4 scale, while pain was assessed using a 100-mm visual analog scale.
Duration	14 days
Outcome Measures	Rduction in smell, pain, discharge, surrounding cellulitis, and bacterial colonization
Baseline Characteristics		All patients (N= 47)
	Age, years (range)	25-93
	Mean age, years	61
	Female	36
	Malignant lesions	20
	Non-malignant lesions	27
Results	Malodor improved substantially during treatment, with the proportion of patients reporting moderately or extremely offensive odor decreasing from 64% at baseline to 11% at day 7 and 4% at day 14. Median pain scores decreased significantly from 3.7 at baseline to 2.0 at day 7 and 1.0 at day 14 (p< 0.001). Cellulitis and discharge scores also decreased significantly over the 14-day treatment period (p< 0.0001 for both). Anaerobic organisms were isolated from 25 wound swabs at baseline and from only 1 wound swab after 14 days of treatment. The reduction in anaerobic organism cultures was statistically significant (p= 0.0006), while no significant reduction in aerobic organisms was observed. No significant differences were observed between patients with malignant and nonmalignant lesions for clinical or bacteriologic outcomes.
Adverse Events	One patient withdrew due to a burning sensation after gel application, one additional patient reported mild stinging but continued treatment, and two patients experienced slight bleeding during dressing changes.
Study Author Conclusions	We conclude that the previously described deodorizing effect of topical metronidazole gel is accompanied by a decrease in lesion pain, in discharge surrounding cellulitis, and in wound colonization by anaerobic bacteria. The use of 0.75% metronidazole gel appears effective and there is no evidence of bacterial contamination posing a problem when a tube remains in use for several days. The patient's awareness of smell underlines the need for sensitive psychological care of patients with fungating wounds.
Critique	The study's open design and lack of a control group limit the ability to attribute improvements solely to the treatment. The subjective nature of smell assessment and the small sample size may affect the reliability of the results. However, the study provides valuable insights into the practical application of topical metronidazole gel for managing malodorous lesions in a clinical setting.

References:
[1] Finlay IG, Bowszyc J, Ramlau C, Gwiezdzinski Z. The effect of topical 0.75% metronidazole gel on malodorous cutaneous ulcers. J Pain Symptom Manage. 1996;11(3):158-162. doi:10.1016/0885-3924(95)00164-6

A Double-blind Study of the Efficacy of Metronidazole Gel in the Treatment of Malodorous Fungating Tumours
Design	Double-blind placebo-controlled trial N= 11
Objective	To assess the value of topical metronidazole gel preparation in the palliation of the offensive odour of fungating tumours
Study Groups	Metronidazole gel (n= 4) Placebo gel (n= 5)
Inclusion Criteria	Patients with open fungating primary or metastatic tumours producing an offensive odour graded at least 6/10 on a visual analogue scale by both the patient and medical staff
Exclusion Criteria	Not specified
Methods	Patients were randomized to receive either 0.8% metronidazole gel or placebo gel applied once daily for 6 days in a double-blind, placebo-controlled trial. This was followed by a 5-day open-label phase during which all patients received metronidazole gel. Doses ranged from 3.75 to 15 g/day based on lesion size and remained constant for each patient. Lesion odor was assessed daily by both the patient and an investigator using 0–10 visual analogue scales.
Duration	11 days total (6 days double-blind phase, 5 days open assessment phase)
Outcome Measures	Subjective odour assessments by patients and medical staff
Baseline Characteristics		All patients (N= 11)
	Mean age, years (range)	68 (51-85)
	Female	10
Results	Among 11 enrolled patients (9 evaluable), mean odor scores in the placebo group remained above 6 during the initial 6-day treatment period. In the metronidazole group, mean patient-assessed odor scores decreased from 7.8 to 5.0 and mean staff-assessed scores decreased from 8.5 to 4.3 by day 6. During the subsequent 5-day open-label phase, patients initially assigned to placebo experienced reductions in mean odor scores from 6.8 to 1.2 (patient assessment; p< 0.005) and from 6.6 to 1.1 (staff assessment; p< 0.005) after receiving metronidazole gel. Patients who received metronidazole throughout the study continued to improve, with mean odor scores decreasing to 2.3 (patient assessment) and 1.5 (staff assessment) by day 11. Overall, odor improvement from baseline to day 11 was significant by both patient and staff assessment (p< 0.001).
Adverse Events	No treatment-related adverse events or side effects were reported.
Study Author Conclusions	The results of this small double-blind randomized study indicate a trend in favor of topical 0.8% metronidazole gel over placebo in palliation of offensive smelling tumors. Metronidazole gel is safe, effective and less toxic than orally administered metronidazole. We recommend daily cleaning and redressing for 7 days followed by a 5-day course of topical 0.8% metronidazole gel applied daily at a dose of 1 g/cm2.
Critique	The study's small sample size limits the statistical significance of the findings. The moderate improvement in patients treated with placebo gel may relate to daily cleaning and redressing of tumours. The trial was ethically halted due to significant improvement in the treatment group, which may introduce bias in the results.

References:
[1] [1] Bower M, Stein R, Evans TR, Hedley A, Pert P, Coombes RC. A double-blind study of the efficacy of metronidazole gel in the treatment of malodorous fungating tumours. Eur J Cancer. 1992;28A(4-5):888-889. doi:10.1016/0959-8049(92)90142-o

The use of metronidazole gel to control the smell of malodorous lesions
Design	Open, uncontrolled study N= 68
Objective	To evaluate the effectiveness of topical 0.8% metronidazole gel in controlling the smell of malodorous lesions
Study Groups	All patients (N= 68)
Inclusion Criteria	Patients with malodorous lesions treated with topical 0.8% metronidazole gel
Exclusion Criteria	Not specified
Methods	Patients with malodorous lesions were treated with topical 0.8% metronidazole gel. Treating clinicians completed a questionnaire documenting patient diagnosis, previous treatments for malodor, treatment duration, time to response, and overall treatment effectiveness (completely successful, reasonably effective, or ineffective), as well as comparison with prior therapies.
Duration	Treatment periods varied from four days to 15 months
Outcome Measures	Control of foul smell
Baseline Characteristics	Treatment duration ranged from 4 days to 15 months, with most patients treated for 1–2 months. Additional baseline patient characteristics were not reported.
Results		All patients (N= 68)
	Completely controlled smell	34 (50%)
	Reasonably effective	31 (46%)
	Ineffective	3 (4%)
	Onset of effectiveness ranged from 1 to 30 days, with most patients reporting benefit within 2 days. Thirty-six assessments reported the gel compared favorably with previous treatments, while two reported it was less favorable.
Adverse Events	One patient with an infected leg ulcer experienced skin irritation after seven days of treatment. No other adverse events were reported.
Study Author Conclusions	The malodorous smell associated with fungating tumours and sloughy lesions can be a very distressing additional problem, particularly for terminally-ill patients. It appears to be reduced, and in this study often eliminated, by topical metronidazole gel. Comparison with other previously used treatments was very subjective, but also seemed to favour the gel.
Critique	The study's open, uncontrolled design limits the ability to draw definitive conclusions about the gel's effectiveness. The subjective nature of odor assessment and lack of monitoring of lesion appearance are limitations. However, the study suggests potential benefits of metronidazole gel in managing malodorous lesions.

References:
[1] [1] Newman V, Allwood M, Oakes RA. The use of metronidazole gel to control the smell of malodorous lesions. Palliat Med. 1989;3(4):303-305. doi:10.1177/026921638900300412