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Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
International Journal of Current Microbiology and Applied Sciences
ISSN: 2319-7706 Volume 4 Number 2 (2015) pp. 1002-

Original Research Article

Comparison efficacy of azithromycin vs. doxycycline in patients
with acne vulgaris
Ameneh Yazdanfar1* and MahsaSaleki2
1Department of Dermatology , School of medicine, Hamedan University of Medical Sciences, Hamedan, Iran 2Department of clinical psychology, Islamic Azad University, Science and research center, Tehran, Iran *Corresponding author A B S T R A C T
Comparing the efficacy of doxycycline and azithromycin in the treatment of patients with acne vulgaris. A total of 120 patients with moderate to severe acne vulgaris parti cipated in this randomized, double-blinded clinical trial and were ssigned to two groups (azithromycin and doxycycline). global scoreswere determined and recorded at baseline. Patients were followed up for three months Clinical assessment was made at baseline and at the end of each month and a global score was determined at each visit. Data was analyzed using K e y w o r d s
SPSS, P val ue <0.05 was considered significant. There was no significant difference between the two groups in terms of demographic data and baseline global scores. Based on global acne grading system, mean percentage of improvement of the lesions was 75.33% in azithromycin group and 73.23% in doxycycline group. statistical analysis showed that at the end of the first and second months, azithromycin was more eff ective than doxycycline and the difference was found significan (P=0.005) for the second month, that might reflect the faster and more effective improvement of ac ne with azithromycin, although the difference wasn't significant at the end of the treatment period. Side effects for Doxycycline was 7 (11.7%) for gastrointestinal a nd3 (5%) for dermatologic that was higher than azithromycin 2 (3.3%) and 1 ( 1.7%) respectively. Our results showed that azithromycin a long acting macroli de has faster and more effective improvement with lower side effects and can be a suitable alternative for doxycycline in treatment of acne vulgaris. Acne vulgaris is a multifactorial disorder of primarily considered an adolescence disease pilosebaceous unit. Clinical presentations (1). Characteristics of this disorder include, vary from mild acne with comedones to systemic inflammatory disease. Although pustules and nodules, deep pustules or acne might affect all age groups, it is psuedocysts and sometimes scarring. Acne Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
has been reported to be most prevalent in 14-17 years old females (45% of them are affected) and 16-19 years old males (35% of Without treatment, acne vulgaris might lead them are affected). In cases with very mild to complications such as inflammatory acne, it is considered a physiologic problem which is found in nearly 24% of female hyperpigmentation teenagers. Female patients present with acne painful nodules, nodular hypertrophic scars, earlier than males due to lower puberty age. cystic lesions and …etc. It might also result The disease improves gradually after 20-25 years, although in 7-17% of patients it hemorrhagic nodules. In rare cases, there persists after 25 years. Acne might persist to might be sinus tracts between deep nodules fourth decade in 1% of male and 5% of or pustules. Lesions in severe acne vulgaris female patients (2). might become very painful, chronic and refractory to treatment and even cause psychological complications particularly in pathogenesis of acne vulgaris: increase in young females (7). keratinocytes of pilosebaceouse follicle, Mild cases of acne are treated using topical change in microbial floraof the skin agents such as retinoids or topical (proliferation of Propionibacterium acnes) antibiotics. Systemic antibiotics including and inflammation (3). Impact of genetic doxycycline are used in treatment of moderate and moderate to severe acne, mild monozygotic and dizygotic twin studies. acne in depressive and dysphoric patients, They showed that the number of comedones and PIH. During the past three decades, oral and the severity of acne is similar in monozygotic twins in contrast to dizygotic tetracyclines (doxycycline and …) and twins (4). A study reported 45% frequency macrolides have been used in treatment of of acne in the parents of boys affected with inflammatory acne, which have required acne while only 8% of parents of healthy administration of several doses daily for a boys had acne. Patients with persistent acne long period (at least 6 months) due to short after 30 years were found to have stronger half-life. In addition, systemic antibiotics family history than those with adolescence might result in several side effects such as gastrointestinal disturbances. Azithromycin is a derivative of Erythromycin with a long Association of severe acne with XXY half-life and thus it can be prescribed in less syndrome has been reported (6). Studies on frequent doses and according to the studies, various races have also showed the impact it has minor side effects, is cost effective of genetic and environmental factors and well tolerated with a high patient together. Acne in African-Americans is compliance rate (8,12). more severe than Caucasians. In addition, severity of acne in Japanese is found to be lower than Caucasians. Incidence of acne investigated the role of azithromycin in has been shown to increase in Eskimos treatment of acne and found that it was changing their diet from fish to processed effective in more than 80% of the cases, foods containing saturated lipids. Same while other therapeutic agents including findings have been seen in Japanese tetracycline, erythromycin, minocycline and immigrants in Hawaii taking American diet doxycycline were averagely effective in Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
77.1% of the cases, however, the difference Given the high prevalence of acne in wasn't statistically significant (9). adolescence particularly in females, and the mentioned literature review, we decided to In another study in 1998, Gruber et al conduct a randomized clinical trial with the aim of comparing the effect of azithromycin azithromycin and minocycline in acne and doxycycline in treatment of moderate to vulgaris. Satisfactory results were found in 75.8% of patients treated by azithromycin and 70.5% of patients receiving minocycline Materials and Methods
at the end of the treatment period. Both antibiotics were well tolerated, minor This double- blinded randomized clinical adverse effects were found in 10.3% of trial was conducted on patients with patients in azithromycin group and 11.7% in moderate to severe acne vulgaris minocycline group. They concluded that in acne treatment, azithromycin is at least as Referred to Farshchian Hospital . Diagnosis effective and tolerable as minocycline (10). was confirmed due to clinical criteria. Patients with multiple papules, pustules and In the study of Fernandez et al in 1997, nodules or scars on face or trunk were patients were satisfied by azithromycin considered to have moderate to severe acne. treatment, no side effects was observed and The severity of acne was determined up to 80% improvement was found after according to global acne grading system four weeks of treatment (11). Kapadia and Talib in their study in 2004 found significant Department of Harvard University. Study improvement in more than 82.9% of patients population consisted of all patients with after four weeks of treatment with moderate to severe acne vulgaris attending azithromycin. Maximum improvement was dermatology clinic and department of detected after 12 weeks of treatment. Farshchian Hospital. Adverse effects including nausea, and heart burn were only seen in 11.4% of cases (13). Patients who met the diagnostic criteria were enrolled in the study if they didn't have a Rafiei and Yaghubi in 2006 investigated history of taking systemic and topical therapeutic effects of tetracycline and treatment for their acne during the past four azithromycin in acne patients. Their results and two weeks respectively and hadn't showed considerable improvement in both received oral isotertinoin for the past 6 groups, while azithromycin was found to be months. Female patients all required to have somewhat more effective than tetracycline a negative pregnancy test and were asked to in reducing inflammatory lesions (84.7% vs. use a safe contraception method other than 79.8%). They concluded that azithromycin OCP during the study period. Exclusion is a safe and efficient therapeutic choice in criteria were history of drug sensitivity, inflammatory acne (15). In another study by medical diseases including endocrine or Lucky et al in 2008, azithromycin was gastrointestinal, shown to result in significant improvement hyperandrogenism manifestations in girls. in 80% of patients after four weeks of After taking informed consents, patients treatment, without causing any serious side were enrolled in the study and randomly assigned to two treatment groups: case improvement was found in only 53% of group received 250 mg azithromycin daily Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
and control group received 100 mg azithromycin (1.7%), however. No patients doxycycline daily for three months. All demonstrated neurologic side effects. patient received instructions about correct method of taking the drugs. Clinical assessment was made at baseline and at the treatment is moderate to good in 95% of end of each month and a global score was patients in azithromycin group and 93.3% of determined at each visit. The score for each patients in doxycycline group and the area (Local score) is calculated by difference isn't significant. multiplying a factor assigned to each area of the body (according to GAGS) in the grade According to the table, change in mean of severity of the lesions (0-4). global score from baseline to the end of the third month of therapy was from 24.35 to Global score is the sum of local scores. A 6.51 in doxycycline group and from 24.91 to score of 0 means no lesions; 1-18 is 6.15 in azithromycin group, showing similar considered mild acne; 19-30, moderate acne; efficacy for two drugs. The difference 31-38, severe acne; and higher than 39 very between mean global scores at baseline and severe acne. Drug side effects including at the end of the first and third months not gastrointestinal, dermatologic signs and symptoms were however, at the end of the second month checked and recorded during each visit. azithromycin group had a significantly Patients were asked to evaluate the treatment lower mean global score than doxycycline at the end of the third month by grading: 0, that was significant (P=0.005). worse; 1, no change; 2, mild improvement; 3, moderate improvement; 4, considerable Result and Discussion
Statistical analysis showed no significant Study was designed as double blinded so difference between the two groups regarding that patients were not informed of the study structure and researchers didn't know about the type of the treatment each patient was comparison of the results between the two receiving and just studied the manifestations groups was more precise. As mentioned, few of the disease and complications of the patients were excluded from the study due to treatment. Medications were prescribed by medication side effects or inability to afford dermatology attending and then patients azithromycin and were substituted with new were referred to the research unit. Data was analyzed using SPSS. Mean global Mean GS at the end of each month of treatment was significantly decreased when Qualitative variables were compared using compared with baseline which indicates the chi-2 test. As shown on the table, gastrointestinal side effects are more Moreover, statistical analysis showed that at frequently seen with doxycycline (11.7%) the end of the first and second months, than azithromycin (3.3%). azithromycin was more effective than doxycycline and the difference was found According to the table, dermatologic adverse significant for the second month that might effects of doxycycline (5%) is higher than reflect the faster and more effective Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
improvement of acne with azithromycin, per week in the third month. The second although the difference wasn't significant at group took doxycycline twice a day for the the end of the treatment period. first month, and daily for the second and third months. Clinical response to therapy Fernandez and Obregon in 2001 investigated was similar in the two groups and persisted efficacy of azithromycin in acne treatment. 3 months after discontinuation of the In their study a total of 99 inflammatory treatment. Three cases of diarrhea were episodes of acne were treated in 79 patients reported in azithromycin group while two using several antimicrobial medications patients in doxycycline group developed photosensitivity. This study suggested that minocycline, and doxycycline. Patients who azithromycin is at least as effective as could not tolerate any of the mentioned doxycycline in treatment of acne (14). drugs were treated using azithromycin. Consistently in our study, gastrointestinal Azithromycin was administered as 250 side effects were found in azithromycin mg/day. Side effects of all drugs were group including 2 cases with abdominal pain evaluated. It was shown that azithromycin and nausea, and dermatologic side effects was effective in 85.7% of patients while the were seen in doxycycline group including other three antibiotics had anaverage two cases of photosensitivity and one case efficacy of 77.1%; however, the difference wasn't statistically significant (9). Rafiei and Yaghoobi in 2006 compared Kapadia and Talib in 2004 studied the effect tetracycline and azithromycin in treatment of 250 mg azithromycin daily for 12 weeks of acne on 290 patients for three months. on 35 patients with moderate to severe acne Azithromycin was administered 500 mg/day and found considerable improvement in for 3 consecutive days per week on the first 82.9% of them with maximum improvement and 250 mg/day every other day for the next (more than 80%) being recorded after 12 weeks of treatment. Side effects including improvements of the lesions in both groups, nausea and heart burn were only seen in 4 however, azithromycin was slightly more (11.4%) patients. This study reported daily effective than doxycycline in reducing 250 mg azithromycin as a safe therapeutic inflammatory lesions (84.7% vs. 79.7%) and regimen for acne with minor side effects it was concluded that azithromycin is a safe (13). Their study period was 3 months and effective alternative in treatment of similar to ours and they also found inflammatory acne (15). maximum improvement after 12 weeks of therapy. They reported gastrointestinal Study population in their investigation was adverse effects of azithromycin in 4 patients larger than ours which is more appropriate while we foundonecase of abdominal pain statistically. The schedule in their study was and one case of nausea in our study. 3 consecutive days for azithromycin and every other day for doxycycline, but in our Yucelten in 2005 compared the efficacy of study both drugs were administered daily. azithromycin and doxycycline in acne Lucky et al (2008) studied the effect of treatment on 50 patients assigned randomly azithromycin 500 mg/day and doxycycline to two therapy groups: azithromycin group 100mg/day on 70 patients with acne. After 2 received azithromycin 500 mg/day on 3 months of therapy, satisfaction rate was 60% consecutive days per week in the first, on 2 consecutive days in the second and on 1 day azithromycin group. Therapeutic effect was Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
other day with doxycycline 200 mg daily on azithromycin groups, respectively (14). 80 patients in two groups of 40 patients each Study population was similar to our study; containing 20 male and 20 female patients. however, they administered azithromycin Therapeutic effect of the drugs after four 500 mg/day and doxycycline 100 mg/day for months was 81.1% in azithromycin group three months. Nevertheless it is interesting and 76% in doxycycline group and the that they found azithromycin to be difference was not statistically significant. Treatment side effects in doxycycline group doxycycline while in our study the efficacy included skin rash and photosensitivity in was similar and only in second month of 18% and headache in 5%. In azithromycin administration was significant. Muron in 2009 studied the effect of azithromycin and neurologic adverse effects were found in doxycycline on acne treatment in 16-18 10% and 2%, respectively (18). In consistent years old adolescents for a six-month period. to our study, patients in this investigation were equally assigned to the two groups and azithromycin and ninety other were given the number of male and female patients in 100 mg doxycycline daily. the two groups was similar. Frequency of Therapeutic effect of the two drugs was doxycycline group and 2% in azithromycin nearly 79% and similar. Side effects were group in this study; however, no cases of found in 15% of the patients in doxycycline neurologic complications were seen in our group including abdominal pain and vomiting and 5% of patients in azithromycin group including nausea (16). Efficacy of the Ellis and Krach in a study compared the medications in this study was similar to ours effect of 250 mg/day azithromycin and 100 (79%) and also the reported adverse events mg/day doxycycline in treatment of acne for were almost like our findings in the a three-month period. Therapeutic response twogroups in terms of type (gastrointestinal was similar and nearly 78.5% in both groups and dermatologic). Knaggs et al in 2011 and persisted for 3 months after treatment studied the effect of azithromycin and discontinuation. Nausea and vomiting was doxycycline in 40 patients for 2 months. reported in four patients in doxycycline Twenty five patients received 100 mg/day group and two patients in azithromycin doxycycline and fifteen patients received group. Photosensitivity was seen in four 250 mg azithromycin every other day. patients in doxycycline group but not Therapeutic effect in both groups was azithromycin group. Patients in this study almost 71%. Patient's satisfaction for were 15 to 28 years old (19), while in our treatment was 70% in doxycycline group and 82% in azithromycin group. Side effects Therapeutic effect in this study was close to in doxycycline group included skin rashes in our results (78.5%). 10% of the patients while in azithromycin skin rashes were found in 4% (17). Mean improvement of acne in our study Treatment period was 2 months in this study according to the global acne grading system while it was 3 months for our study. was 74% in both study groups highlighting Patient's satisfaction level in our study was the high efficacy of both of these drugs. 95% for azithromycin and 93.3% for doxycycline. In a study in 2012 Speroff et according to GAGS scale was performed at al compared azithromycin 500 mg every the end of each month of treatment and Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
showed higher efficacy of azithromycin in it costs more than older antibiotics which is comparison to doxycycline during the first a compliance limiting factor in patients from two months in acne treatment, although at lower economic levels. Results of the the end of the three-month period the effect presents study and previous investigations of the both drugs was almost similar. demonstrated that azithromycin, a long acting macrolide, can be an acceptable Subjective evaluation of the two treatment alternative for the classic doxycycline in regimens asked from patients showed that treatment of inflammatory acne and given nearly 94% assessed therapeutic effect the long half-life and low complications, it has higher patient compliance while its satisfaction. Therefore, azithromycin is a long acting drug with minor side effects and high patient compliance. On the other hand, Table.1 Frequency of gastrointestinal side effects in the study population
Gastrointestinal side effects As shown on the table, gastrointestinal side effects are more frequently seen with doxycycline (11.7%) than azithromycin (3.3%). Table.2 Frequency of dermatologic side effects in the study population
Dermatologic side effects According to the table, dermatologic adverse effects of doxycycline (5%) is higher than azithromycin (1.7%), however. No patients demonstrated neurologic side effects. Table.3 Comparison of patients' evaluation about their treatment in the two groups
Patients' evaluation Accordingly patients' evaluation of treatment is moderate to good in 95% of patients in azithromycin group and 93.3% of patients in doxycycline group and the difference isn't significant. Int.J.Curr.Microbiol.App.Sci (2015) 4(2): 1002-1009
Table.4 Comparison of mean final score of the patients at the end of first,
second and third months of treatment
Acknowledgement
9) Fernandez. Obregon, A. Azithromycin for Present study is done in Department Dermatology of Farshchian hospital of 10) Gruber F, Grubisic – Greblo H, kastelam Hamedan university of medical sciences. M, Brajac I, Lenkovic M, Famolo G, Azithromycin Compared with minocyline References
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