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Table of Contents 
Year : 2012  |  Volume : 57  |  Issue : 4  |  Page : 279-281
Efficacy of 2% metronidazole gel in moderate acne vulgaris

1 Department of Dermatology, Sina Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
2 Researcher, Tabriz University of Medical Sciences, Medical Faculty, Tabriz, Iran
3 Department of Pharmaceutics, Sina Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

Date of Web Publication29-Jun-2012

Correspondence Address:
Rohollah F Fouladi
Researcher, Tabriz University of Medical Sciences, Faculty of Medicine, Tabriz
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.97666

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Background: Acne vulgaris is an inflammatory disease of the pilosebaceous units. Various systemic and topical options are available for its treatment. Aims: This study aimed to evaluate the efficacy of 2% metronidazole gel in acne vulgaris. Materials and Methods: Double-blind, randomized, placebo-controlled, split-face clinical trial. Seventy young adults with moderate acne vulgaris received 2% metronidazole gel on the right side of their face and placebo on the left side of their face twice daily for 8 weeks. The number of inflamed and noninflamed facial lesions and side effects of treatment were documented on weeks 1, 2, 4, and 8. The patients' overall satisfaction was recorded at the end of the study. For statistical analysis we used the repeated-measures analysis, the chi-square test, Fisher's exact test, and the independent-samples t-test as appropriate. Results: Counts of inflamed and noninflamed facial lesions were comparable between the two sides at baseline. The number of the lesions was significantly lower on the metronidazole-treated side at all follow-up visits. Erythema and oily face decreased by 85.7% and 87.1%, respectively, on the metronidazole-treated side. Mild burning sensation and dryness on the metronidazole-treated side was reported by 3.4% and 22.9% of the patients, respectively. Eighty-eight percent of the patients were satisfied with the results of treatment on the metronidazole-treated side. Conclusions: Metronidazole gel (2%) is an effective, safe, and well-tolerated topical medication for moderate acne vulgaris.

Keywords: Acne vulgaris, efficacy, 2% metronidazole gel

How to cite this article:
Khodaeiani E, Fouladi RF, Yousefi N, Amirnia M, Babaeinejad S, Shokri J. Efficacy of 2% metronidazole gel in moderate acne vulgaris. Indian J Dermatol 2012;57:279-81

How to cite this URL:
Khodaeiani E, Fouladi RF, Yousefi N, Amirnia M, Babaeinejad S, Shokri J. Efficacy of 2% metronidazole gel in moderate acne vulgaris. Indian J Dermatol [serial online] 2012 [cited 2023 Oct 3];57:279-81. Available from:

What was known? 1. There is only limited number of studies with application of topical metronidazole in acne vulgaris with heterogeneous results. 2. Propionibacterium acnes has traditionally been considered a metronidazole-resistant microorganism.

   Introduction Top

Acne vulgaris is a common dermatologic disease that is usually managed by application of topical preparations, systemic medications, or a combination of the two. [1],[2],[ 3] Antibiotics play a pivotal role in treatment. However, the emergence of new resistant strains or cross-resistance, development of various side effects, and poor tolerability are factors that sometimes limit their usefulness. [4],[5],[6],[7],[8] Successful management of acne needs careful selection of anti-acne agents according to clinical presentation and individual patient needs. [9] Today, different topical therapies are available for patients with acne vulgaris, including comedolytic agents, anti-inflammatory medications, antibiotics, and even herbal preparations. [10],[11],[12],[13],[14],[15],[ 16] Metronidazole is an antibacterial agent that is available in the form of an aqueous gel for topical application. Its mechanism of action in acne vulgaris is thought to be associated with its anti-inflammatory, immunosuppressive, and/or antimicrobial properties. [17],[18] There is a very limited number of studies on the topical use of metronidazole in acne vulgaris. [19],[20] This study aimed to evaluate the efficacy of 2% metronidazole gel in moderate facial acne vulgaris.

   Materials and Methods Top

Study design and participants

In this double-blind, placebo-controlled, split-face clinical trial conducted at a referral teaching clinic of dermatology, 78 young adults (age range: 18-30 years) with moderate facial acne vulgaris (acne grade III) [21] were recruited from September 2010 through July 2011. Reasons for exclusion were: acne secondary to other problems; pregnancy or intention to become pregnant; breastfeeding; another dermatological disease of the face; significant systemic disease, especially colitis; treatment with oral isotretinoin within the previous 1 year; taking any other acne treatment; history of having taken any medication that could interact with metronidazole within the previous 3 months; and known hypersensitivity to the study medication. The study protocol was approved by the Ethics Committee of Tabriz University of Medical Sciences. The study was conducted in accordance with the Declaration of Helsinki and good clinical practices guidelines. All patients provided written informed consent before participation.


Type of facial skin was determined by a Sebumeter® SM 815 (Courage and Khazaka, Cologne, Germany) on five different sites of the face and, according to previously established criteria, [22] The patients were classified into two groups based on their skin type; with normal/dry (non-oily) skin or with oily skin. Topical 2% metronidazole gel was applied on the right side of the face twice daily for 8 weeks in all patients, while a similar-appearing water-based neutral gel (placebo) was simultaneously applied on the left side of the face in the same fashion. The metronidazole gel and placebo were filled in similar tubes that were marked 'right' or 'left,' indicating the side on which they should be applied. During the study period, only a caregiver who was not involved in the experiment was aware of the contents of the tubes; the patients and the examiner were blind to the topical compounds.

The 2% metronidazole gel was prepared in the Tabriz University Department of Pharmacy. Carbomer, as the gelifiant, was added to preserved water with methyl alcohol and propylparaben. Twenty-four hours later, the other components, including glycerin and polyethylene glycol, as well as metronidazole, were added to the prepared solution. The organoleptic and physical stability of both preparations were tested and confirmed.

The patients came for follow-up examinations on day 2 and weeks 1, 2, 4, and 8. All patients completed the study period. Counts of inflamed and noninflamed lesions, presence of erythema, the facial skin type (oily or not), and any possible complications/side effects were assessed and documented on each visit by a skilled dermatologist. On the last visit, the patients were asked about their satisfaction with the treatment.

Statistical analysis

Statistical evaluation was done using SPSS® for Windows v 18.0 (SPSS Inc., Il, USA). Data were shown as frequency (percentage) or mean±standard deviation (SD). The repeated-measures analysis, the Chi-square test, Fisher's exact test, or the independent-samples t-test were used as appropriate. P≤0.05 was considered statistically significant.

   Results Top

Seventy patients, 26 males (37.1%) and 44 females (62.9%), with a mean age of 22.6±4.28 years (range: 18-30 years) were enrolled in this study. The mean duration of acne in the study population was 3.03±1.54 years (range: 2-5 years). Counts of inflammatory, noninflammatory, and overall (inflammatory plus noninflammatory) facial lesions are summarized and compared between the two sides on different occasions in [Table 1]. The two sides were comparable with regard to the baseline counts. On the other occasions, decrease of the mean lesion counts was significantly more on the right side of the face than on the left side (repeated-measures analysis, P<0.001 on all occasions). At the last visit, the number of cases with erythema and oily skin on the metronidazole-treated side had decreased by 85.7% and 87.1%, respectively (P<0.001), whereas there was no change on the contralateral side. The side effects on the metronidazole-treated side were mild burning sensation in 22 patients (31.4%) and mild dryness of skin in 16 other patients (22.9%). However, none of these side effects led to discontinuation of treatment and all the participants completed the study. At the last visit, 88% of the patients stated that they were satisfied with the results of treatment on the right side, whereas none reported satisfaction with the treatment results on the left side (P <0.001).
Table 1: Counts of the lesions on both sides of the face at the different visits

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   Discussion Top

In the present study, 2% metronidazole gel was shown to be an effective and safe topical medication for treating moderate acne vulgaris. There are only limited numbers of studies that have similarly examined the effect of metronidazole topical application on acne vulgaris, and the results have been variable. While Tong et al. found no significant benefit of 0.75% metronidazole gel over placebo in reducing counts of inflamed and noninflamed lesions in mild to moderate acne vulgaris, [19] Bannatyne reported significant efficacy of the drug in a similar setting. [20] Nielsen compared 2% metronidazole and 5% benzoyl peroxide cream in acne vulgaris and reported that 2% metronidazole cream was significantly better than the 5% benzoyl peroxide gel. It was also shown that 2% metronidazole and 5% benzoyl peroxide cream were both equal in efficacy to systemic oxytetracycline therapy. [23] Our findings are in concordance with the results of Nielsen's study. The high efficacy of 2% metronidazole gel is despite the fact that Propionibacterium acnes has traditionally been considered a metronidazole-resistant microorganism. [24],[25],[26],[ 27] So, mechanisms other than microbicidal action may underlie the therapeutic effect of metronidazole, such as anti-inflammatory, immunosuppressive, and anti-itching actions, as well as the inhibition of free radical generation by human neutrophils. [28] Nevertheless, development of resistant strains is always a worry and the use of therapeutic regimens that incorporate agents with complementary but different mechanisms of action is a possible strategy in this regard. [29] Recurrence of acne after drug withdrawal is another important issue that should be examined in future studies.

   References Top

1.Hsu P, Litman GI, Brodell RT. Overview of the treatment of acne vulgaris with topical retinoids. Postgrad Med 2011;123:153-61.  Back to cited text no. 1
2.Kraft J, Freiman A. Management of acne. CMAJ 2011;183:E430-5.   Back to cited text no. 2
3.Smith EV, Grindlay DJ, Williams HC. What's new in acne? An analysis of systematic reviews published in 2009-2010. Clin Exp Dermatol 2011;36:119-22.  Back to cited text no. 3
4.Ingram JR, Grindlay DJ, Williams HC. Management of acne vulgaris: An evidence-based update. Clin Exp Dermatol 2010;35:351-4.   Back to cited text no. 4
5.Cook D, Krassas G, Huang T. Acne-best practice management. Aust Fam Physician. 2010;39:656-60.  Back to cited text no. 5
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7.Hassanzadeh P, Bahmani M, Mehrabani D. Bacterial resistance to antibiotics in acne vulgaris: An in vitro study. Indian J Dermatol 2008;53:122-4.  Back to cited text no. 7
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10.Percy SH. Safety and efficacy of adapalene gel 0.1% in acne vulagaris: Results of post-marketing surveillance study. Indian J Dermatol Venereol Leprol 2003;69:277-80.  Back to cited text no. 10
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18.Nishimuta K, Ito Y. Effects of metronidazole and tinidazole ointments on models for inflammatory dermatitis in mice. Arch Dermatol Res 2003;294:544-51.   Back to cited text no. 18
19.Tong D, Peters W, Barnetson RS. Evaluation of 0.75% metronidazole gel in acne-a double-blind study. Clin Exp Dermatol 1994;19:221-3.  Back to cited text no. 19
20.Bannatyne RM. Metronidazole, its bioactive metabolites and acne. Curr Med Res Opin 1999;15:298-9.  Back to cited text no. 20
21.Burke BM, Cunliffe WJ. The assessment of acne vulgaris-the Leeds technique. Br J Dermatol 1984;111:83-92.  Back to cited text no. 21
22.Youn SW, Kim SJ, Hwang IA, Park KC. Evaluation of facial skin type by sebum secretion: Discrepancies between subjective descriptions and sebum secretion. Skin Res Technol 2002;8:168-72.  Back to cited text no. 22
23.Gamborg Nielsen P. Topical metronidazole gel. Use in acne vulgaris. Int J Dermatol 1991;30:662-6.  Back to cited text no. 23
24.Bannatyne RM, Harnett NM. Metronidazole and acne. Acta Derm Venereol 1976;56:307-8.  Back to cited text no. 24
25.Smith MA, Alperstein P, France K, Vellozzi EM, Isenberg HD. Susceptibility testing of Propionibacterium acnes comparing agar dilution with E test. J Clin Microbiol 1996;34:1024-6.  Back to cited text no. 25
26.Werner H, Krasemann C, Kandler R, Wandmacher G. Metronidazole sensitivity of anaerobes. A comparison with other chemotherapeutics. MMW Munch Med Wochenschr 1980;122:633-6.  Back to cited text no. 26
27.Denys GA, Jerris RC, Swenson JM, Thornsberry C. Susceptibility of propionibacterium acnes clinical isolates to 22 antimicrobial agents. Antimicrob Agents Chemother 1983;23:335-7.  Back to cited text no. 27
28.Akamatsu H, Oguchi M, Nishijima S, Asada Y, Takahashi M, Ushijima T, et al. The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: A possible mechanism of action of metronidazole in rosacea and acne. Arch Dermatol Res1990;282:449-54.  Back to cited text no. 28
29.Gamborg Nielsen P. Topical metronidazole gel. Use in acne vulgaris. Int J Dermatol 1991;30:662-6.v  Back to cited text no. 29

What is new? In patients with moderate acne vulgaris, 2% metronidazole gel is an effective, safe and well-tolerated topical medication.


  [Table 1]

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