Table 1.

Comparison of different studies conducted in various countries regarding study design, grouping, treatment dosage, duration and main results

Author (Year)	Study Design*	Grouping and Dosage	Main results
Ullah et al., 2014 (21)	Randomized, 386 patients, 12 weeks	Group 1: Azithromycin 500 mg/day, 4 consecutive days monthly; Group 2: Doxycycline 100 mg/day	25.9% response in azithromycin group, 66.8% response in doxycycline group, Doxycycline was a better option for acne treatment with a significant difference.
Rassai et al., 2013 (22)	Investigator-blind, randomized, 148 patients, 8 weeks	Group 1: Azithromycin 500 mg /day, 3 days a week plus oral Levamisole 150 mg /day, 2 days a week; Group 2: Azithromycin 500 mg/day, 3 days a week	Azithromycin plus levamisole was significantly more effective than azithromycin alone in reducing inflammatory acne lesions.
Hasibur et al., 2013 (23)	Open-label, non- comparative, 82 patients, 24 weeks	Pulsed oral Azithromycin: 500 mg/day on 3 consecutive days in each week for 1 month with low-dose Isotretinoin: 0.3 mg/kg/day for 6 month	Complete cure in 80 (97.56%) patients, Low-dose isotretinoin plus oral azithromycin pulse can be effective in moderate to severe acne.
Moravvej et al., 2012 (24)	Investigator-blind, randomized, 60 patients, 12 weeks	Group 1: Azithromycin 500 mg/day three times a week; Group 2: Doxycycline 100 mg/day. All patients used topical tretinoin cream every other night.	Both groups showed significant and similar improvements in inflammatory lesion count with mild and transient side effects.
Kayhan et al., 2012 (25)	Randomized, 60 patients, 12 weeks	Group 1: oral Azithromycin 500 mg/day on 3 consecutive days followed by 7 days rest (a 10-day cycle); Group 2: Doxycycline 100 mg/day. Topical adapalene gel was added to the systemic treatment in both groups.	Both treatments were safe and effective with significant and similar improvement in the quality of life scale scores and minimal side effects.
Babaeinejad et al., 2011 (26)	Double-blind, randomized, 100 patients, 12 weeks	Group 1: Azithromycin: 500 mg/day, on 4 consecutive days per month; Group 2: Doxycycline: 100 mg/day	Both antibiotics were effective with minor complications the in treatment of moderate acne. Doxycycline was significantly more effective in patients above 18 years.
De et al., 2011 (27)	Open-label, non- comparative, 66 patients, 16 weeks	Combination of low-dose Isotretinoin 0.3 mg/kg/day and pulsed oral azithromycin 500 mg/day on 3 consecutive days every 2 weeks	93.9% complete clearance and 11.3% disease relapse, The combination of low-dose isotretinoin and oral azithromycin was an effective treatment for severe acne with acceptable adverse-effects.
Maleszka et al., 2011 (28)	Double-blind, randomized, 240 patients, 12 weeks	Group 1: Azithromycin 500 mg/day for 3 days in the first week, followed by 500 mg tablets weekly to complete 10 weeks of treatment; Group 2: 2 Doxycycline 100 mg capsules on the first day, then once a day during 12 weeks of treatment	Similar reduction in number of lesions with both azithromycin and doxycycline, No difference was observed in the incidence of side effects between the two treatment groups.
Antonio et al., 2008 (29)	Open-label, non- comparative, randomized, 57 patients, 12 weeks	Azithromycin: 500 mg on 3 consecutive days with intervals of 7 days without medication	Azithromycin was well tolerated with a significant reduction in the number of lesions. The majority of adverse effects were related to the gastrointestinal and central nervous systems.
Innocenzi et al., 2008 (30)	Open-label, non- comparative, 46 patients, 12 weeks	Azithromycin: 500 mg thrice weekly for 12 weeks. Plus: 0.1% topical adapalene (gel or cream) once daily in the evening, and benzoyl peroxide (gel) once daily in the morning.	Significant improvement and reduction in lesions, Safe and effective treatment regimen for moderate acne with excellent patient compliance. Reported side effects were diarrhea and abdominal pain.
Wahab et al., 2008 (31)	Randomized, 60 patients,12 and 20 weeks	Group 1: Isotretinoin: 0.5-1 mg/kg for 5 months; Group 2: Azithromycin: 500 mg 3 days a week for 3 months. Topical adjuvant therapy e.g. erythromycin lotion initially and then adapalene was given in both the groups.	Both treatments were useful for moderate and severe acne. Isotretinoin appeared to be superior to weekly pulse dose of azithromycin. Mild nausea and abdominal discomfort were reported in Azithromycin group.
Bardazzi et al., 2007 (32)	Open-label, non-comparative, 52 patients, 8 weeks	Azithromycin: 500 mg thrice weekly	Remarkable improvement in 90.4% of patients, Safe and effective treatment regimen for acne in adolescents, with excellent patient compliance, Gastrointestinal intolerance was reported by three patients (5.8%).
Basta-Juzbašić et al., 2007 (33)	Open-label, randomized, 93 patients, 24 weeks	3 dosage regimens of azithromycin: Group 1: 4.5 g total dose in 7 weeks; Group 2: 6.0 g total dose in 10 weeks; Group 3: 7.5 g total dose in 13 weeks, A 3-day course of 500 mg/day followed by 500 mg/week for another 6 weeks in group 1, 9 weeks in group 2, and 12 weeks in group 3. Subjects were allowed to apply a keratolytic lotion topically twice a day.	Cure rate: 36.11% in group 1, 58.82% in group 2 and 55.88% in group 3. Azithromycin in a total dose of 6.0 g in 10 weeks was beneficial in the treatment of papulopustular acne with few side effects and good patient compliance.
Ghoshal et al., 2007 (34)	Randomized, 61 patients, 12 weeks	Group 1: topical adapalene (0.1%) gel once daily at bedtime and 1 FTU for the entire face; Group 2: 500 mg oral azithromycin for 3 consecutive days in a week; Group 3: combination of the two therapies. Patients washed their face with soap for three to four times a day.	Although combination therapy showed highest reduction in the number of inflammatory lesions, there was no significant difference in the efficacy of the three treatment groups.
Naieni et al., 2006 (35)	Investigator-blind, randomized, 58 patients, 12 weeks	Three different Azithromycin regimens: Group 1: 5 consecutive days, 500 mg on the first day and 250 mg/day for another 4 days per month; Group 2: 500 mg/day for 4 consecutive days per month; Group 3: 250 mg/day thrice weekly.	Low dose azithromycin was as effective as a high dose with more compliance and fewer side-effects. Diarrhea was the only complication in three patients of group 3.
Rafiei et al., 2006 (36)	Investigator-blind, randomized, 290 patients, 12 weeks	Group 1: Azithromycin 500 mg for 3 consecutive days a week for 1 month, then 250 mg every other day for the following 2 months; Group 2: Tetracycline 1 g with similar protocol	Azithromycin response (84.7%) was slightly higher in reducing inflammatory lesions compared with tetracycline (79.7%). Similar rate of GI side effects (11%) were reported in both groups.
Kus et al., 2005 (37)	Investigator-blind, randomized, 45 patients, 20 weeks	Group 1: Azithromycin 500 mg/day on 3 consecutive days per week in the first, on 2 consecutive days per week in the second, and on 1 day per week in the third month; Group 2: Doxycycline 100 mg twice a day for the first month and once a day for the second and third months	Significant and similar improvement of acne lesions in both drugs,
Kapadia et al., 2004 (38)	Open-label, non- comparative, 35 patients, 12 weeks	Azithromycin 500 mg orally thrice weekly for 12 weeks, 0.05% tretinoin cream was applied only to the face	Remarkable improvement in 82.9% of patients in the first 4 weeks, Adverse events were reported by 11.4% of patients. Azithromycin was a safe and effective treatment for acne vulgaris with excellent patient compliance.
Singhi et al., 2003 (39)	Non-randomized, 62 patients, 12 weeks	Group 1: azithromycin was administered 500 mg daily for 3 consecutive days in a 10-day cycle, with seven drug-free days in each cycle; Group 2: doxycycline 100 mg daily. Topical erythromycin was prescribed to all patients	77.26% improvement in azithromycin group and 63.74% in the doxycycline group, The combination of azithromycin with topical erythromycin was significantly better with lower side effects compared to doxycycline with topical erythromycin.
Parsad D et al., 2001 (40)	Randomized, 50 patients, 12 weeks	Group 1: Doxycycline 100 mg/day; Group 2: Azithromycin 500 mg/day for 4 days per month. Topical 0.05% Tretinoin cream was prescribed to all patients.	A monthly dose of azithromycin was as effective as daily doxycycline.
Fernandez-Obregon, 2000 (41)	Retrospective, 79 patients, 10 weeks	Individuals that were unable to tolerate tetracycline, erythromycin, minocycline, and doxycycline, were treated with azithromycin 250 mg three times a week. Most patients also used topical care.	Significant improvement was noted in 4 weeks in all agents, while azithromycin was significantly better with a greater than 80% reduction in inflammatory acne lesions (85.7%) vs. an average of 77.1% for all other agents.
Gruber et al., 1998 (42)	Open-label, 72 patients, 6 weeks	Group 1: oral azithromycin 500 mg for 4 days every 10 days, for a total of four cycles; Group 2: minocycline 100 mg/day for 6 weeks	75.8% treatmentresponse with azithromycin and 70.5% with minocycline; Azithromycin was at least as effective as minocycline in the treatment of comedonic and papulopustular acne with well and similar tolerance.