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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 37-40

Comparison of efficacy of oral azithromycin with oral minocycline in the treatment of acne vulgaris


1 Department of Dermatology, Venereology and Leprosy, Bharati Vidyapeeth University Medical College, Pune, Maharashtra, India
2 Department of Dermatology, James Paget University Hospital, Gorleston-on-Sea, Great Yarmouth, NR31 6LA, UK

Date of Web Publication28-Jul-2017

Correspondence Address:
Vidyadhar R Sardesai
102 Alliance Nakshatra, 48 Tulshibagwale Colony, Sahakar Nagar No. 2, Pune - 411 009, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_2_17

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  Abstract 


Background: Acne vulgaris is a common skin disease seen primarily in adolescents and young adults. As the treatment involves long-term therapy with antibiotics, an agent with a long half-life can be very useful in increasing the compliance. Objectives: The objective of this study was to evaluate the efficacy of a pulse dose of azithromycin and compare it with daily dose of minocycline in the treatment of acne vulgaris. Materials and Methods: This prospective, randomized, open-label, comparative study was conducted on sixty patients with moderate-to-moderately severe (Grade II and III) acne vulgaris. Patients were randomly assigned to two treatment groups, A and B. Patients in Group A received 50 mg minocycline orally daily whereas patients in Group B were given 500 mg azithromycin orally once a day for 3 consecutive days/week. Both the groups were advised topical application of 2.5% topical benzoyl peroxide gel in the night. The total duration of treatment was 3 weeks. All the patients were evaluated at the end of 3 weeks. Statistical analysis was done using Wilcoxon signed-rank test and Mann–Whitney U-test. Results: Group A showed a reduction in lesional count of 39.7% for noninflammatory papules, 65.11% for inflammatory papules, and 52.22% for pustules. Similarly, Group B showed 30.39%, 54.69%, and 57.76% reduction in lesional count for noninflammatory papules, inflammatory papules, and pustules, respectively. Conclusions: Both minocycline and azithromycin were equally effective and safe for the treatment of acne vulgaris.

Keywords: Acne, azithromycin, minocycline


How to cite this article:
Sardesai VR, Deka YT. Comparison of efficacy of oral azithromycin with oral minocycline in the treatment of acne vulgaris. Clin Dermatol Rev 2017;1:37-40

How to cite this URL:
Sardesai VR, Deka YT. Comparison of efficacy of oral azithromycin with oral minocycline in the treatment of acne vulgaris. Clin Dermatol Rev [serial online] 2017 [cited 2017 Sep 26];1:37-40. Available from: http://www.cdriadvlkn.org/text.asp?2017/1/2/37/211780




  Introduction Top


Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit that affects predominantly adolescents and young adults. It is characterized by noninflammatory, open or closed comedones and inflammatory papules, pustules, and nodules. It results from androgen-induced increased sebum production, altered keratinization, inflammation, and bacterial colonization of hair follicles by Propionibacterium acnes.[1]

Acne is a complex disease with multifactorial pathogenesis and considerable variation in severity.[2] Acne develops in the pilosebaceous unit, composed of epidermal cells lining the hair follicle and the sebaceous gland.[3] Acne represents obstruction and inflammation of the sebaceous follicles, a subtype of pilosebaceous units.[4]

Antibiotic therapy has been an important part of acne management worldwide for the past 40 years, but acne is not an infection in the classic sense.[5] However, inflammatory, moderate-to-severe acne vulgaris is treated with systemic antibiotics. The rationale is an effect on P. acnes as well as the intrinsic anti-inflammatory properties of these antibiotics.[6]P. acnes produces an extracellular lipase which hydrolyzes sebum triglycerides to form glycerol and free fatty acids. These further induce comedone formation and inflammation. P. acnes also releases neutrophil chemotactic factor which attracts neutrophils and releases inflammatory mediators.

Macrolides, like erythromycin, were used earlier as oral therapy for treating acne. However, due to increasing trends of resistance, search for newer antibiotics began. Many studies have shown macrolides, especially azithromycin, to be very effective for the treatment of acne vulgaris.

There have been previous studies comparing azithromycin with tetracyclines, such as doxycycline. Minocycline has also been studied and tested individually for treating acne. It has been found to be a good and effective choice of antibiotic for acne. However, on extensive review of literature, very few studies have been done to compare azithromycin with minocycline.

Objectives

The objective of this study was to compare and evaluate the efficacy of azithromycin and minocycline in the treatment of acne vulgaris Grade II and III.


  Materials and Methods Top


This was a prospective, randomized, open-label, comparative study done in a tertiary care hospital. After obtaining Institutional Ethics Committee clearance and written informed consent, a total of sixty newly diagnosed patients with acne Grade II and III belonging to the age group of 15–25 years and both genders were included in the study. A detailed history was taken which included the onset, duration, and progress of condition, past history of similar complaints, and history of any other underlying illness. Patients with underlying hormonal imbalance causing acne (such as polycystic ovarian disease), drug-induced acne, contraindications to oral azithromycin or minocycline, and those already on treatment were excluded from the study.

The allocation of the first patient was randomized to either of the groups and then rest of the patients were alternatively allocated to two groups, A and B. Group A was given oral minocycline 50 mg daily for 3 weeks and Group B was given oral azithromycin as a pulse dose of 500 mg for 3 consecutive days/week for 3 weeks. Both the groups were given topical 2.5% benzoyl peroxide (BPO) gel at night. A detailed clinical examination was done which included counting the acne lesions on the face on day 0 and day 21, by dividing the face into four quadrants. The lesions were divided into noninflammatory papules (which included open, closed comedones and skin-colored papules) and inflammatory papules (which included erythematous papules and pustules). Photographic evidence was also taken on the same days. The percentage of reduction in the lesional count at the end of 21 days was considered as primary end point measurement. Both the patients and investigators were aware of the treatment given. Wilcoxon signed-rank test was used to calculate P value in each group (intragroup) whereas Mann–Whitney U-test was used to calculate the P value while comparing the two groups (intergroup). For the above tests, minimum lesion count, i.e., minimum number of lesions counted in a patient of that group, maximum lesion count, i.e., maximum number of lesions counted in a patient of that group, and the median lesion count were calculated.


  Results Top


A total of sixty newly diagnosed patients, 26 males and 34 females with acne Grade II and III belonging to the age group of 15–25 years, were included in the study. There were 12 males and 18 females in the minocycline group and 14 males and 16 females in azithromycin group. The mean age was 19.33 years in minocycline group and was 19.47 years in azithromycin group.

Significant improvement was noted in patients belonging to both the groups [Table 1], [Figure 1] and [Figure 2]. After applying Wilcoxon signed-rank test, it was found that the P value was <0.001. Hence, reduction of lesions was statistically significant in both the treatment groups [Table 2] and [Table 3].
Table 1: Reduction in lesional count

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Figure 1: Patient treated with azithromycin - day 0 and day 21

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Figure 2: Patient treated with minocycline - day 0 and day 21

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Table 2: Reduction in lesional count in azithromycin group

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Table 3: Reduction in lesional count in minocycline group

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However, when both the groups were compared statistically using Man–Whitney U-test, the difference was not significant [Table 4].
Table 4: Azithromycin versus minocycline: Comparison of reduction in lesional count

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No significant side effects such as severe gastrointestinal (GI) upset, jaundice, chest pain, or palpitations were reported in the azithromycin group, and GI disturbances, hypersensitivity, jaundice, and pigmentation were not reported in the minocycline group.


  Discussion Top


Erythromycin is the first macrolide used in the treatment of acne vulgaris. It has been used much less frequently owing to the GI side effects.[7] It also has a short half-life requiring frequent administration. There are a lot of known drug interactions associated with erythromycin. Therefore, the newer macrolides such as azithromycin began to be used more frequently. It has fewer GI side effects, longer half-life, and good tissue penetration. Its extensive distribution in the tissues allows recommendation of pulse-dose regimen to improve the compliance.

Azithromycin is an azalide of the macrolide group of antibiotics. Derived from erythromycin, it has an aza-methyl substitution (insertion of a nitrogen atom) in the macrolide ring. The addition of the second amine group resulted in important advantages over erythromycin, including greater tissue penetration and an extended half-life.[8] Azithromycin inhibits protein synthesis by binding to 50S ribosomal subunit and preventing translocation. It is primarily a bacteriostatic drug, but in higher concentration can be bactericidal. The most common treatment-related side effects involve the GI tract, including diarrhea, nausea, and abdominal cramping.[9] On the other hand, minocycline, a semi-synthetic, second-generation tetracycline, has a better pharmacokinetic profile, and compared with doxycycline, it is not phototoxic.[10] It can be taken more conveniently as once or twice daily dose compared with the generally more frequent dosing of other tetracyclines. Minocycline being lipophilic achieves greater tissue concentration and is thought to be more effective than doxycycline in acne, a view held by the Global Alliance. Tetracyclines are bacteriostatic that are considered broad-spectrum antibiotics because they are active against a wide range of aerobic and anaerobic Gram-positive and Gram-negative bacteria. The mechanism of action behind the antibiotic properties of tetracyclines is mainly related to their ability to bind to the bacterial 30S ribosomal subunit and inhibition of protein synthesis. The most common known side effects of minocycline are nausea, vertigo, and mild dizziness.[11] Some systemic side effects such as GI disturbances, tooth discoloration, enamel hypoplasia, autoimmune hepatitis, and drug hypersensitivity syndrome may occur. Cutaneous brown-black hyperpigmentation may be diffuse (muddy skin syndrome) or varying patterns involving the photoexposed areas and pretibial area or lesional pigmentation including scars.

Many studies have shown macrolides, especially azithromycin, to be very effective for the treatment of acne vulgaris. There have been previous studies comparing azithromycin with tetracyclines, such as doxycycline. However, on extensive review of literature, very few studies have been done to compare azithromycin with minocycline. Minocycline has been studied and tested individually for treating acne. It has been found to be a good and effective choice of antibiotic for acne. Knowing that minocycline has a lot of advantages over other tetracyclines, it was imperative to study whether it is superior to azithromycin in the treatment of acne. BPO has been an important component of topical therapy for acne vulgaris for more than five decades due to its ability to markedly reduce P. acnes and inflammatory acne lesions and its ability to moderately reduce noninflammatory acne lesions. BPO is directly toxic to bacteria. It does not alter bacterial structure, specific enzymes, and/or nuclear and cytoplasmic proteins unlike other antibiotics. As a result, BPO has not been associated with the development of P. acnes' resistance. The addition of BPO to antibiotic therapy reduces the risk of bacterial resistance.[12] Therefore, both the groups were given topical benzoyl peroxide 2.5% gel.

It was observed that, in 3 weeks, all patients showed statistically significant reduction in their acne lesions. Therefore, it can be deduced that both these antibiotics are effective for treating acne [Table 1],[Table 2],[Table 3].

In an earlier study, Gruber et al. compared azithromycin with minocycline in the treatment of acne comedonica and papulopustulosa. Azithromycin was administered as a single oral dose (500 mg/day) for 4 days in four cycles for every 10 days and minocycline was administered 100 mg daily for 6 weeks.[13] There were no significant differences between these two acne treatments in terms of reduction of the number of lesions. It was concluded that azithromycin is as effective and well tolerated as minocycline in the treatment of acne comedonica and papulopustulosa.

Limitations of the study are lack of blinding and duration of the treatment and follow-up. The duration of treatment should have been longer, i.e., 6 weeks. However, to ensure proper follow-up and avoid dropouts, the duration of the study was fixed to 3 weeks.


  Conclusions Top


Both azithromycin and minocycline were effective in the treatment of moderate and moderately severe acne vulgaris. Although statistically not significant, both noninflammatory and inflammatory lesions respond better to minocycline whereas pustules decrease more with azithromycin. There were no reported side effects with either of the drugs in the given time period of 3 weeks. Hence, treatment regimen can be tailored according to the patient's needs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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. 1
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2.
Oberemok SS, Shalita AR. Acne vulgaris, I: Pathogenesis and diagnosis. Cutis 2002;70:101-5.  Back to cited text no. 2
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3.
Lee DJ, Van Dyke GS, Kim J. Update on pathogenesis and treatment of acne. Curr Opin Pediatr 2003;15:405-10.  Back to cited text no. 3
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4.
Kubba R, Bajaj AK, Thappa DM, Sharma R, Vedamurthy M, Dhar S, et al. Pathogenesis of acne. Indian J Dermatol Venereol Leprol 2009;75 Suppl 1:S5-9.  Back to cited text no. 4
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Ozolins M, Eady EA, Avery AJ, Cunliffe WJ, Po AL, O'Neill C, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: Randomised controlled trial. Lancet 2004;364:2188-95.  Back to cited text no. 5
    
6.
Ochsendorf F. Systemic antibiotic therapy of acne vulgaris. J Dtsch Dermatol Ges 2006;4:828-41.  Back to cited text no. 6
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7.
Millikan LE. Acne therapy: Old wine in new vessels-the promise (and pitfalls) of new drug deliveries and regimens. Expert Rev Dermatol 2009;4:191-4.  Back to cited text no. 7
    
8.
Kim M, Welch T. Update on azithromycin and cardiac side effects metastatic pulmonary calcification. Southwest Respir Crit Care Chron 2014;2:48-51.  Back to cited text no. 8
    
9.
Ochsendorf F. Minocycline in acne vulgaris: Benefits and risks. Am J Clin Dermatol 2010;11:327-41.  Back to cited text no. 9
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10.
Garrido-Mesa N, Zarzuelo A, Gálvez J. Minocycline: Far beyond an antibiotic. Br J Pharmacol 2013;169:337-52.  Back to cited text no. 10
    
11.
Kubba R, Bajaj AK, Thappa DM, Sharma R, Vedamurthy M, Dhar S, et al. Acne in India: Guidelines for management-IAA consensus document. Indian J Dermatol Venereol Leprol 2009;75 Suppl 1:1-62.  Back to cited text no. 11
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12.
Rosso JQ. What is the role of benzoyl peroxide cleansers in acne management? Do they decrease propionibacterium acnes counts? Do they reduce acne lesions? J Clin Aesthetic Dermatol 2008;1:48-51.  Back to cited text no. 12
    
13.
Gruber F, Grubisic-Greblo H, Kastelan M, Brajac I, Lenkovic M, Zamolo G. Azithromycin compared with minocycline in the treatment of acne comedonica and papulo-pustulosa. J Chemother 1998;10:469-73.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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