Clinical and microbiological pattern of intertrigo

Background: Intertrigo is a common disorder affecting many flexural areas of the body with significant morbidity. Objectives: To determine the clinical pattern of intertrigo. To determine bacterial and fungal pathogens associated with intertrigo. To assess the antibacterial and antifungal sensitivity pattern of the responsible organisms. Methods: A total number of 230 patients with intertrigo attending dermatology unit were included in the study after ethical clearance. Laboratory investigations were done to identify the etiologic agent and their sensitivity pattern. Results: Majority of patients (75%) belonged to 20-60 years of age. Male to female ratio was 1.15:1. Remarkable proportion (52%) presented with the involvement of more than one intertriginous area. The most common site involved was toe web space (63%) in particular 4 th toe web space. Of all positive bacterial cultures 45% revealed Staphylococcus aureus (MSSA+MRSA) followed by CNSA (Coagulase negative Staphylococcal aureus ), diptheroids and pseudomonas. The majority of MSSA (Methicillin sensitive Staphylococcus aureus ) isolates (91%) were sensitive to cloxacillin and MRSA (Methicillin resistant Staphylococcus aureus ) to teicoplanin (85%). CNSA isolates showed considerable proportion of sensitivity to vancomycin (37%) and majority of diptheroids isolates were sensitive to penicillin(87%). All isolates (100%) of pseudomonas were sensitive to gentamicin. Of all positive fungal cultures, candida species constituted the majority (35%) followed by fusarium species (33%) and dermatophytes (30%). Overall


Introduction
Intertrigo, or intertriginous dermatitis, may be defined as inflammation resulting from moisture trapped in skin folds subjected to friction 1 .It is a common skin condition and can affect many areas of the body such as axilla, submammary, retroauricular, groin, perineum, intergluteal and interdigital spaces 1 .Among all these variants interdigital intertrigo (including toe or finger webs) is the commonest variant 2 .
Intertrigo may be symptomatic as a painful, exudative, macerated, erosive, inflammatory process which is sometimes malodorous or asymptomatic incidental finding 3 .It can result in significant morbidity and mortality with serious systemic infections.Studies have shown that 60% of cellulitis of the legs are associated with toe web intertrigo 4 .
Intertrigo can be infected with fungi and bacteria, as compromised skin facilitates the entry of microorganisms 1 .Following is a list of commonest fungal species associated with intertrigo; Candida species: C.albicans, C.tropicalis, C.parapsilosis, C.glabrata, C.guilliermondii 3 .
Studies related to microbiological aspects of intertrigo are lacking in Sri Lanka even though this condition is commonly seen in Sri Lankan clinical setup.

Objectives
1. To determine the clinical pattern of intertrigo.2. To determine the bacterial and fungal pathogens associated with intertrigo.
3. To assess the antibacterial and antifungal sensitivity pattern of the responsible organisms in intertrigo.

Methodology
Study design: Descriptive cross-sectional study.
Study setting: Dermatology Unit, National Hospital, Colombo, Sri Lanka.

Sample selection:
Patients who attended or were referred to the Dermatology Unit, National Hospital of Sri Lanka (Colombo) with intertrigo were recruited into this study after obtaining informed written consent, starting from July 2016.All patients referred to this Unit were at or above the age of 13 years.
Patients who were already on treatment were kept free of topical antifungal drugs and antibiotics for 2 weeks and oral antifungal drugs and antibiotics for 4 weeks before recruiting into the study.
Data were collected according to a preformed questionnaire and patients were subjected to following; Bacteriological studies: This was carried out in Microbiology Department, National Hospital, Sri Lanka and consist of three components.
I. Gram staining: Lesions were cleaned with sterile normal saline and cotton swabs were taken from the lesions.Smears were prepared and stained with gram stain.This was examined under microscope using oil immersion.III.Antifungal sensitivity testing: All the fungi that was isolated, was tested for following commonly using antifungal drugs according to Clinical Laboratory Standard Institute (CLSI) guidelines.Antifungal drugs that were tested include itraconazole, fluconazole and ketoconazole.The results were indicated as minimal inhibitory concentration (MIC) using Enz MIC Tm strips.
For patients who had an involvement of more than one intertriginous area, bacteriological and mycological studies were done from each area separately.

Results
A total of 230 patients with intertrigo were included in the study.Their age ranged from 13 to 89 years, with mean age of 47 (±16) years, median age 48 years and most frequent age of presentation was 42 years.Seventy five percent (n=173) of patients were between 20 to 60 years.
Considering the presentation, 157 (68%) patients presented directly due to intertrigo, on the other hand in 106 (32%) patients, this was an incidental finding(indirect presentation).One hundred and twenty-four patients (54%) presented with 1 st episode,

Sri Lanka Journal of Dermatology
A B Wickramanayake, et al whereas 106 (46%) presented with recurrent episode.Eight patients had a history of recurrence more than 3 times.
Distribution of intertrigo, 135 (58%) patients had 1 site involvement followed by 45 (20%) with two site involvement and 50 (22%) had more than two site involvements.Patients with multiple site involvement each and every site analyzed separately.
In 146 patients with toe web intertrigo, both feet affected in 89 (61%) patients and the commonest affected toe web was 4 th toe web (n=127, 87%).In 23 patients with hand intertrigo, one hand affected in 14 (61%) and it was mainly right hand (n=10).The commonest finger web affected was 3 rd finger web, which affected in 22 (96%) patients.

Antifungal sensitivity pattern
As an overall, fungal culture positivity noted in 126.Among them, commonest species isolated was Candida species (n=44, 35%) followed by Fusarium species (n=41, 33%), Dermatophytes (n=38, 30%), Trichosporon species (n=2, 1.3%) and Exophiala species (n=1,0.7%) Figure 1.A slight male preponderance was noted which is contrary to S. Krishna et al 2 which showed a male to female ratio of 1:3.However Ahamed et al 8 showed  higher preponderance in males in toe web intertrigo (56.7%) which is compatible with our finding of male:female ratio of 1.8:1.The toe webs being the commonest site affected in our study, this explains the overall male preponderance probably secondary to occlusive shoes in men.Area wise distribution is almost the same with the exception of female preponderance in axillary, sub mammary and suprapubic flexural areas.This may be due to anatomical variations.
In our study 58% presented with the involvement of one site followed by 20% and 15% of two sites and

Antifungal sensitivity pattern
Minimal inhibitory concentration (MIC) was measured in microgram per milliliters (ug/ml).MIC 50 and MIC 90 were calculated for itraconazole, fluconazole and ketoconazole Table 5.

Sri Lanka Journal of Dermatology
A B Wickramanayake, et al three site involvements.Majority had the involvement of toe webs (63%) followed by groin and other areas.This is concordance with Krishna et al 2 in which toe web is the commonest site affected.
In toe web intertrigo, bilateral feet involvement and common involvement of 4 th toe web is very well tallied with findings of Ahamad et al 8 and Hassab et al 3 .This is probably secondary to anatomical occlusive nature of 4 th toe web.In finger webs, common occurrence in 3 rd finger web is well described in adams et al 10 .
Predominant involvement of right hand can be elucidated by the right hand dominancy in the majority which leads to increased exposure such as to water as well as increased sweating with exertion of the dominant hand.
Corynebacterium minutissimum is a diptheroid bacillus which causing toe web intertrigo due to its keratolytic properties and may coexist with a dermatophyte infection, particularly in the toe webs 11 .Unfortunately, in our set up we don't have the facilities to isolate C. minutissimum separately; however, diptheroids can be isolated which includes C. minutissimum.We have isolated 21% diptheroidsas an overall and it is the commonest bacteria isolated in toe webs which was 34% (n=27)of all positive cultures (n=79).Pseudomonas species were isolated in 6.5% in overall and 13% in toe webs.This is compatible with the finding of Ahamed et al 8 which isolated 10% of pseudomonas in toe webs.Many studies concluded previous prolong antibiotics and antifungal therapy can predispose to gram negative bacterial intertrigo 7,12 .
Considering the antibiotic sensitivity pattern of organisms, high proportion of MSSA(91%) isolates were sensitive to cloxacillin in concordance with the finding of Hanumanthappa et al 13  According to our findings, highest proportion of pseudomonas species was sensitive against gentamycin (100%) and ciprofloxacin (77%).However, study of Yadav et al 14 South Chhattisgarh in India demonstrated 53% and 51% of sensitive proportion of pseudomonas species to above two antibiotics and highly sensitive ratio in meropenem and imipenem (91%).This different pattern may be due to differences in local antibiotic policies with the consequent development of resistance.However, sensitive proportion to ceftazidime of 54% is compatible with the finding of Yadav et al 14 .
In this study the predominant fungal species isolated was candida species (35%) which is comparable but was relatively lower occurrence than the findings in Krishna et al 2 and Ahamed et al 8 which showed 51.33% and 60% respectively.Isolation of dermatophyte species in 30% is consistent with the study of ahamed et al 8 which demonstrated 31% of dermatophytes.Fascinatingly, fusarium species were isolated in 33% in our study.
Fusarium onychomycois is well recorded in Sri Lanka 15 , on the other hand records related to fusarium intertrigo are lacking in Sri Lanka as well as in international literature except few case reports 16 .Thus, this necessitates the more elaborated studies on this aspect.According to Ranawaka et al 17 , Fusarium toe nail infection is a difficult challenge in eradication with a prolong therapeutic reservoir in nails for 11 months therefore need at least 1 year follow up to confirm the complete cure.This may be also applicable for the intertrigo especially toe webs and may explain the chronic nature of this disease in our set up with recurrence.However, to confirm this assumption more elaborated and comprehensive studies are needed.
Considering, antifungal sensitivity filamentous species such as fusarium followed by dermatophytes

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Clinical and microbiological pattern of intertrigo showed high MIC values comparing to the yeast like candida.On the other hand, MIC of fluconazole for dermatophyte and fusarium is markedly higher comparative to itraconazole and ketoconazole.Higher MIC values for fluconazole have also been reported by some authors previously 18 and indicating higher chances of treatment failure when treated with this drug.Itraconazole and ketoconazole had lower MIC for of dermatophytes and fusarium comparing to fluconazole which indicates that these drugs could be the better option for successful treatment of these infections than fluconazole.Many studies on dermatophytes have reported similar findings with itraconazole and ketoconazole 18 .According to these results among these three Azoles, itraconazole is a better choice for successful treatment of dermatophytes, fusarium and candida infection.
Overall MIC of itraconazole, fluconazole and ketoconazole are high in fusarium species comparing to other fungi which may indicate difficult eradication, prolong treatment and treatment resistance.However, this necessitates further elaborated studies.

Conclusion
Intertrigo is a disease predominantly affecting the age group of 20-60 years, with a slight male preponderance.It can be an incidental finding and can have recurrent episodes.It can involve multiple sites at same time, however the commonest site affected was toe webs with a predilection to 4 th toe web space followed by groins.

Table 5 . Antibiotic sensitivity pattern (S-Sensitive, R-Resistance)
Common bacterial organisms causing intertrigo are Staphylococcus aureus (MSSA+ MRSA) followed by CNSA, diptheroids and pseudomonas species.The majority of MSSA isolates are sensitive to cloxacillin, MRSA to teicoplanin, CNSA to vancomycin, diptheroids to penicillin and pseudomonas to gentamicin.Common fungi result in intertrigo are Candida species followed by fusarium species and dermatophytes.Among Candida species C.albicans is the commonest organism and among dermotophytes, T.mentagrophytes is the commonest organism.MIC of itraconazole, fluconazole and ketoconazole are high in fusarium species comparing to candida and dermatophytes.However, itraconazole and ketoconazole had lower MIC than dermatophytes and fusarium comparing to fluconazole.