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A comparison between the effectiveness oferythromycin, single-dose clarithromycin and

topical fusidic acid in the treatment of

erythrasma

ARTICLE in JOURNAL OF DERMATOLOGICAL TREATMENT SEPTEMBER 2011

Impact Factor: 1.67 DOI: 10.3109/09546634.2011.594870 Source: PubMed

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Oktay Avci

Dokuz Eylul University

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Journal of Dermatological Treatment. 2013; 24: 7074

ORIGINAL ARTICLE

A comparison between the effectiveness of erythromycin,single-dose clarithromycin and topical fusidic acid in the treatment

of erythrasma

OKTAY AVCI, TANER TANYILDIZI & ERGUN KUSKU

Department of Dermatology, Dokuz Eyll University Faculty of Medicine, Izmir, Turkey

AbstractAlthough erythrasma is a supercial skin infection, there is no consensus on the treatment model of erythrasma. Objective: To

compare the efcacy of erythromycin, single-dose clarithromycin and topical fusidic acid in the treatment of erythrasma in a

double-blind, placebo-controlled, randomized trial. Methods: Hundred and fty-one patients over 18 years of age were

included in this study. Patients were randomized and divided into ve groups. They received clarithromycin, erythromycin,

fusidic acid cream, placebo cream or placebo tablets. Patients were evaluated by Woods light reection scores and the initial

score values and the values on the days of 2, 7 and 14 were compared statistically. Results: According to the mean of Woods

light reection scores, the efcacy of fusidic acid cream therapy was signicantly higher than other therapies. When the efcacy

of clarithromycin and erythromycin therapy was compared, clarithromycin therapy was signicantly more effective than

erythromycin therapy at 48 h. However, there was no statistical difference on the days of 7 and 14.Conclusion:Topical fusidic

acid proved to be the most effective treatment; however, clarithromycin therapy may be an alternative regimen in the treatment

of erythrasma because of its efciency and better patients compliance.

Key words: clarithromycin, erythrasma, erythromycin, fusidic acid

Introduction

Erythrasma is a supercial skin infection caused by

Corynebacterium minutissimum and often occurs in

intertriginous areas of the skin such as toe webs

and the inguinal, axillary, inframammary and inter-

gluteal regions (14). It is characterized by erythem-

atous, brown, scaly patches and maceration, and

exhibits coral-red uorescence under Woods light

(58). There is no standard method of treatment for

erythrasma, and a variety of oral, topical and adjunc-

tive therapy models are used (9). In this study, our

aim was to compare the effectiveness of the treatments

with erythromycin, single-dose clarithromycin and

topical fusidic acid with the double-blind, random-

ized, placebo-controlled method in patients with

erythrasma.

Patients and methods

A total of 151 adult patients over 18 years of age with

the diagnosis of erythrasma were involved in this

study. Exclusion criteria comprised pregnancy and

breast-feeding, allergy to macrolides or fusidic acid,

antibiotic and antifungal treatments within the pre-

ceding 2 weeks. Before the study, the approval of the

relevant ethics committees was obtained. In accor-

dance with the Helsinki Declaration of Ethical Prin-

ciples, the patients were informed in writing and

verbally, and informed consents were obtained. Thestudy was designed as a double-blind, placebo-

controlled randomized study. The randomization

was carried out centrally and ve separate groups

were formed. In the rst group, a single dose of

1 g/day of 500 mg clarithromycin tablets was applied.

Correspondence: Ergun Kusku, MD, Department of Dermatology, Dokuz Eyll University, Balcova, 35340 Izmir, Turkey. Tel: 90 232 4123852.

Fax: 90 232 4646309. E-mail: [email protected]

(Received 3 March 2011; accepted 4 May 2011)

ISSN 0954-6634 print/ISSN 1471-1753 online 2013 Informa Healthcare USA on behalf of Informa UK Ltd.

DOI: 10.3109/09546634.2011.594870


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In the second group, 1 g/day dose of erythromycin

tablets was applied for 14 days. In the third group,

placebo tablets were applied for 14 days. In the

fourth group, fusidic acid cream 2% was applied

twice a day for 14 days and, in the fth group, placebo

cream was applied twice a day for 14 days. Thepatients were intructed not to wash the rash for a

24-h-period before their each visit in order not to

remove the coproporphyrin III produced by the

causitive bacteria.

The patients were evaluated for Woods light reec-

tion with a Woods lamp and reection scores were

recorded before and 48 h, 7 days and 14 days after the

treatment. The Woods light reection scores in all

cases of erythrasma, which was localized to the

toe webs, axillary, genitocrural and inframammary

regions were considered as follows: prominent red

uorescence 2; slight red uorescence 1; no

uorescence

0. The evaluation was made by twoindependent physicians who did not know which

patient was randomized into which group, and then

the average values of the scores that were determined

by these two evaluators were calculated. In cases

of erythrasma with bilateral localization, right-side

reection scores were taken into consideration.

Only the patients whose reection score was 2 and

who had a signicant reection were included in this

study. Patients were advised not to use another sys-

temic or topical medication during the treatment

period. Because of the possibility of being found

together and creating exacerbation of clinical symp-

toms, and for diagnostic purposes, direct mycologicalexaminations and cultures from the same areas were

performed. During the follow-up, patients were ques-

tioned about the side effects of the medicaments and,

if present, the adverse effects were recorded.

Statistical analysis

At the end of the study, the scores obtained from the

groups were determined. Statistical analyses were

performed using SPSS 11.5 for Windows (SPSS,

Chicago, IL, USA). Even though the number of

patients was more than 30 in all groups, nonparametric

tests were used as a method of statistical analysis

because the variables were not persistent and the dis-

tributionof data wasnot in accordance with thenormal

distribution in the histogram. Results of descriptive

statistical analysis are presented as mean standard

deviation. A MannWhitneyU-test was used for the

differences between groups, and Pearsons chi-

square analysis and Fishers exact test were used for

the comparisons according to the methods of treat-

ment, and p-values lower than 0.005 (


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partial response 0.5

1 and no response 1.5

2. Accord-ingly, in the rate of the response to treatment at the end

of the 14th day in the erythromycin group, complete

response was determined in 16 patients (53.3%), par-

tial response was determined in 7 patients (23.4%) and

no response was observed in 7 patients (23.4%). In the

clarithromycin group, responses were as follows: com-

plete in 20 patients (66.7%), partial in 8 patients

(26.6%) and no response in 2 patients (6.7%). In

the fusidic acid group, complete response was observed

in 30 patients (96.8%) and partial response was

observed in 1 patient (3.2%) (Table II).

Discussion

Although there is no full consensus in the treatment of

erythrasma, there is a variety of oral, topical and

adjunctive treatment models. These include systemic

applications such as erythromycin, tetracycline, chlor-

amphenicol, clarithromycin and topical applications

including clindamycin solution, Whiteld oinment

consisting of benzoic acid and salicylic acid, antibac-

terial soaps and fusidic acid (913).

In a double-blind, placebo-controlled study in

which oral erythromycin and topical 2% fusidic

acid cream were used in 86 cases of erythrasma, it

was found that the rate of complete response was 77%

in the erythromycin group, 87% in the fusidic acid 2%

cream group and 42% in the placebo group, and no

statistically signicant difference was found between

these treatment modalities (14). In another study, a

twice-daily 14-day application of 2% fusidic acid hadthe success rate of up to 89%, and no recurrence was

seen in the 40th post-treatment week (15). The use of

clarithromycin in the treatment of erythrasma was rst

described in a clinical trial including three cases

of erythrasma with genitocrural localization and a

1-g/day single dose of clarithromycin provided the

regression of pruritus at the 48th hour and a full

recovery in all three of the patients within 2 weeks.

In this study, no serious adverse effect was observed.

Mild abdominal cramps was the only adverse effect

attributable to clarithromycin use. It was concluded

Table I. Average Woods light reection scores at each visit for the

ve groups.

48th hour Day 7 Day 14

Erythromycin 1.250 0.114a 0.700 0.141 0.633 0.143

b,d

Clarithromycin 0.833

0.108

a

0.450

0.110 0.333

0.105

b,c

Fusidic acid 0.419 0.101 0.032 0.032 0.016 0.016c,d

Placebo cream 1.416 0117 1.266 0.128 1.266 0.128

Placebo tablets 1.850 0054 1.683 0.100 1.683 0100

aStatistically signicant difference between the clarithromycingroup and the erythromycin group at the 48th hour (p < 0.05).bStatistically signicant difference between the clarithromycingroup and the erythromycin group on the day 14 (p = 0.154).cStatistically signicant difference between the fusidic acid groupand the clarithromycin group on the day 14 (p < 0.05).dStatistically signicant difference between the fusidic acid groupand the erythromycin group on the day 14 (p < 0.05).

2

1.6

1.2

0.8

0.4

0Pretreatment

A

veragewoodslightreflectionscore

48th hour

Fusicid acid Erythromycin Clarithromycin

Placebo cream Placebo tablets

Treatment duration

Day 7 Day 14

Figure 1. The reduction in the scores within each group. Signicant superiority of oral clarithromycin and topical fusidic acid to oral

erythromycin, placebo cream and placebo tablets (p < 0.05) at the 48th hour. The difference between clarithromycin and erythromycin

disappeared on the 7th day while fusidic acid appeared to be the most effective treatment. On the day 14, fusidic acid was found to be

signicantly more effective than systemic clarithromycin and erythromycin and no signicant therapeutic efcacy was observed between

clarithromycin and erythromycin.

72 O. Avci et al.


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that a single dose of clarithromycin could constitude a

cheap, effective and safe therapy with perfect patients

compliance and tolerability (16).

In our study, the efcacy of fusidic acid cream was

determined to be signicantly higher than all other

methods of treatment. The efcacy of clarithromycin

was determined to be signicantly higher than that of

erythromycin in the rst 48 h, although there was nosignicant difference between their efcacies on the

7th and 14th days. At the end of the 14th day, it was

determined that there was a full recovery in the

majority of patients receiving erythromycin, clarithro-

mycin and fusidic acid. The higher rate of effective-

ness of the clarithromycin when compared with

erythromycin at the 48th hour may be due to a

high dose intake all at once and better bioavailability,

longer half-life, shorter time to reach steady-

state concentration and the lower MIC value of clar-

ithromycin compared with erythromycin. The values

of minimal inhibitory concentration for the Coryne-

bacteriumspecies of clarithromycin are lower than forthe other types of macrolide group antibiotics such as

erythtomycin and azithromycin (17). Hence, clari-

thromycin seems to be much more effective particu-

larly on the Corynebacterium species when compared

with other macrolides. However, there is no clinical

trial investigating the efcacy of clarithromycin in

the treatment of erythrasma except one report

including only three patients (16). The effectiveness

of 1 g/day single dose of clarithromycin in erythrasma

can be explained with its superior features such

as bioavailability, half-life and MIC value when

compared with erythromycin as well as its post-

antibiotic effect. The post-antibiotic effect is dened

as a persistent supression of bacterial developement

following short-term drug administration. However,

there are no previously conducted studies on the

duration of the post-antibiotic effect of clarithromycin

on corynebacteria.

The success rate of 96.8% and the signicantly

higher efcacy of fusidic acid cream treatment com-

pared with the other systemic treatments might be due

to the removal of coproporphyrin III from stratum

corneum during topical applications. In this study,

interdigital erythrasma was detected in the majority of

the patients. It has been reported that systemic ther-

apy alone may be insufcient in patients with inter-

digital erythrasma, and it is necessary to use 2%

clindamycin solution, 2% fusidic acid cream and

Whiteld oinment consisting of 12% benzoic acid

and 6% salicylic acid, and antibacterial soaps in

conjunction with oral erythromycin (9). The resultsof our trial and previous studies give the impression

that topical treatments can affect Woods light reec-

tion scores. Therefore, in future placebo-controlled

trials, a regulation such as an active systemic agent

plus placebo cream or a topical cream containing

active ingredient plus placebo tablets may give

more accurate results and possibly makes the

potential effect of the topical application equal in

each group. Undoubtfuly, the cultivation ofCoryne-

bacterium minutissimum or high-performance liquid

chromatography (18) could provide a much more

objective assesment; our laboratory was unable to

make these investigations and a grading system wasused for the assessment as described before (8,14).

In this study, it was found that 8 of the 30 patients

(26.7%) had abdominal pain and 1 had dyspepsia

receiving erythromycin. Six of the 30 patients (20%)

had the complaint of a metallic taste in the mouth,

2 (6.7%) had abdominal pain and 1 had dyspepsia in

the clarithyromycin group. One of the 30 patients had

pruritus and 1 had dyspepsia in the placebo tablet

group. The results of this study have shown that a

single dose of 1 g/day clarithromycin regimen is

an effective and safe alternative in the treatment of

erythrasma.

Acknowledgements

The authors would like to thank to the following

companies for their support on providing erythromy-

cin, clarithromycin and placebo tablets and fusidic

acid, placebo cream preparations: Kocak Pharmaceu-

tical Company, Mustafa Nevzat Pharmaceutical

Company, Bilim Pharmaceutical Company, Abdi

Ibrahim Pharmaceutical Company and Schering

Pharmaceutical Company.

Table II. Clinical efcacy at the third visit.

Efcacy assessment

Erythromycin Clarithromycin Fusidic acid Placebo cream Placebo tablets

n % n % n % n % n %

Complete response 16 53.3 20 66.7 30 96.8 4 13.3 1 3.3

Partial response 7 23.4 8 26.6 1 3.2 11 36.7 6 20.0

No response 7 23.4 2 6.7 0 0.0 15 50 23 76.6

Total 30 100 30 100 31 100 30 100 30 100

A study on the treatment of erythrasma 73


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Declaration of interest: The authors report no

conicts of interest. The authors alone are responsible

for the content and writing of the paper.

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