Background:Studies revealed that severity of atopic dermatitis correlates with colonization by S.aureus and the density of bacteria and antibiotic resistance is one of the factors in S.aureus recolonization.
Objectives:We aimed to determine the pattern of colonization with different subtypes of S.aureus in patients with atopic dermatitis and its correlation with SCORAD (Scoring Atopic Dermatitis) index.
Materials and Methods:We studied 114 sample cultures from normal skin, nose and active lesions of 38 patients with atopic dermatitis to detection of Staphylococcus aureus colonization and MRSA (methicilin resistance Staphylococcus aureus) subtypes with E test. The severity of the disease was identified by the SCORAD criteria. Logistic regression analysis was used for the evaluation of the coexistence between MRSA colonization and SCORAD index in these patients.
Results:We studied 114 sample cultures from 38 children (73% boys, 27% girls) with atopic dermatitis. Mean age of the patients was 19 ± 22.7 months. Mean objective SCORAD was 37.8 + 16.4 (range: 15-80). Twelve patients (31.6%) had mild, 18 patients (47.4%) had moderate and 8 patients (21%) had severe SCORAD.\r\nSeventeen patients (44%) were colonized by S. aureus in the nose, 14 (36%) on skin lesions, and 8 (21%) on healthy skin. Among all the cultures, MSSA was noted in 26 (22%) and MRSA was noted in 13 (11%). There was a significant relationship between SCORAD index and colonization of nose and active lesions with Staphylococcus aureus (P value = 0.001). We found MRSA only in patients with moderate SCORAD.
Conclusions:This study shows lower rate of S. aureus colonization in atopic dermatitis cases but similar rate of MRSA colonization in comparison with previous studies . A higher rate of MRSA colonization was found in patients with moderate SCORAD.
On the basis of these studies, we designed this study in order to identify correlation between SCORAD in AD and methicillin resistance pattern in S.aureus.
3. Materials and Methods
In a cross-sectional study, we studied 38 patients with AD (diagnosed based on Hanifin and Rajka criteria) (7), who had been referred to the allergy clinic in Mofid children’s hospital in Tehran, Iran, with simple nonrandomized consecutive sampling.
A questionnaire was filled out for every patient and the severity of diseases was graded with the SCORAD system (8). The SCORAD was classified into three groups (mild = lower than 25, moderate ranged from = 25-50, severe = higher than 50). Informed consent was signed by the patients. Then three samples for S.aureus detection were taken from the nasal cavity, healthy and AD lesions and the specimens were inoculated in salt agar manitol milieu (Merck, Lot: VM 136304 016). Following 24 hours of incubation, suspected colonies were studied for Coagolase (Rabbit Plasma With EDTA, IRAN, Lot: 9012), DNAase (Merck, Lot: VM 324249 364) and Ureas enzymes (Merck, Lot, VM 938192 515). Subsequently, isolated S.aureus was examined with E test (AB, BIODISK) for methicillin resistance pattern and MSSA and MRSA subtypes were characterized.
The data was analyzed by SPSS (11.5 version) and Logistic regression analysis was used to study the coexistence between methicillin resistance pattern and the SCORAD index.
4.1. Patients' Characteristics
The patients' age ranged from 2 to 108 months. Twelve patients had mild SCORAD, 18 patients had moderate and 8 had severe SCORAD. Other Characteristics are summarized in Table 1.
|Age (mo), mean (range)||19 (2-108)|
|Male gender, No. (%)||28 (73.3)|
|Age at presentation (mo) (range)||5 (1-24)|
|Family history of atopy (%)||27 (72%)|
|Mean objective SCORAD, mean (range)||37.8 (15-80)|
4.2. S.aureus and MRSA Colonization
Altogether, 18 patients (47%) were colonized by S.aureus in different sites of sampling. The number and percentage of colonized patients in different sampling sites and the ratio of MRSA colonization in different sites is summarized in Table 2. Among all the cultures (114 samples), MSSA (Methicillin Sensitive Staphylococcus aureus) was noted in 26 (22%) and MRSA was noted in 13 (11%). Of positive S.aureus cultures, MRSA accounted for 33% of all S.aureus isolates.
|Site of Sampling||No. and Percentage of S. aureus Colonized Patients, No. (%)||Ratio of MRSA Colonization among S. aureus Colonized Patients, Ratio (%)|
|Healthy skin||8 (21)||4/8 (50)|
|Nasal cavity||17 (44)||4/17 (23)|
|AD lesions||14 (36)||5/14 (35)|
The percentage of S.aureus colonization in different sites of sampling in patients with mild, moderate and severe AD is shown in Table 3. There was a significant relationship (P = 0.001) between AD severity and S.aureus colonization in nasal cavity and AD lesions.
|Normal Skin||AD Lesions||Nose|
|P. Value||> 0.05||0.001||0.001|
The rate of S.aureus, MRSA and MSSA colonization in patients with mild, moderate and severe AD has been compared in Table 4. We found MRSA only in AD patients with moderate SCORAD (in 5 patients).
|Mild (12)||Moderate (18)||Severe (8)|
|S. aureus||2 (16.7%)||10 (55.6%)||6 (75.0%)|
|MRSA||0 (0.0%)||5 (27.8%)||0 (0.0%)|
|MSSA||2 (16.7%)||5 (27.8%)||6 (75.0%)|
Patients with atopic dermatitis are prone to S.aureus colonization and infection. Recent studies showed the high rate of S.aureus colonization in these patients, especially in AD skin lesions and the nasal cavity, which ranged between 76–100%, compared to 2–25% in healthy subjects (9-11). This is likely the result of a combination of host factors including skin barrier dysfunction as well as impaired host immune responses in AD (12, 13). Comparing the above-mentioned studies, we found lower rate of overall S.aureus colonization in our patients (47%). Lo et al. (14) in Taiwan found that S.aureus colonization rates were 50% in their patients which is similar to our results.
Our study showed a higher rate of S.aureus colonization in the nasal cavity and AD lesions compared to healthy skin (44%, 36%, and 21%, respectively). Nasal carriage of S.aureus in the general population is approximately 10–45% and is higher among patients with AD (39–100%) (15, 16). In our study, among positive cultures, MRSA accounted for 33% of all S.aureus isolates. Recent trends indicate an increasing incidence of CA-MRSA (community-associated MRSA) in the general population (17), and some studies have showed the high rate of MRSA in AD (14, 18, 19). A study by Lo et al. have shown that 60% of S.aureus isolates from 20 children with AD and skin and soft-tissue infections were classified as MRSA but the percentage of MRSA isolates among all S.aureus-colonizing isolates was 28.3% (14).
Ortega-Loayza et al. analyzed 141 cultures from 93 pediatric dermatology patients in North Carolina, where 66% of the cultures that had been taken from children with atopic dermatitis. S.aureus was recovered from 97 cultures of which 32% were MRSA (19). Schlievert et al. have recently tested a small group of AD isolates for methicillin resistance S.aureus and have found that 25% were MRSA (18). Chung et al. in a South Korean clinic noted a 75.4% incidence rate of S.aureus colonization in children with atopic dermatitis, with 18.3% incidence of CA-MRSA in skin lesions (20).
Some studies have shown lower colonization rate for MRSA. In a study done by Huang et al. on 31 patients with AD, 7.4% of AD skin lesions and 4% of the nares with positive cultures for S.aureus were resistant to methicillin (21).
Our results revealed significant correlation between SCORAD score and colonization with S.aureus in AD skin lesions and the nasal cavity (P = 0.001). Some other studies have found that the severity of dermatitis correlates with the density of S.aureus colonization on AD skin lesions and anti S.aureus antibiotics have been shown to mitigate the severity of AD (22, 23). Kedzierska et al. in 87 AD patients showed a positive correlation between the colonization density of S.aureus in AD skin lesions and the severity of AD, and they reported no significant correlation between density of bacteria in healthy skin and SCORAD (24). Hon et al. also found that the anterior nares are an important site for S.aureus and that nasal colonization was associated with more extensive lesions and a higher SCORAD index (25). The authors in one study have suggested that the production of inflammatory cytolysins and high-level superantigens by CA-MRSA increases their ability to cause extensive AD infections (18).
Tomi et al. and Zoller et al. have shown that the increased AD severity correlates with the presence of a super antigen produced by S.aureus (25-27). However, our study could not conclude a relationship between type of S.aureus (MSSA or MRSA) and SCORAD index since we found MRSA just in moderate SCORAD and none of the isolated S.aureus in severe and mild groups were MRSA. One study designed by Chiu et al. to determine the distribution of the bacterial virulence factors (such as; toxic shock syndrome toxin, staphylococcal enterotoxins A–E, G–K, enterotoxin gene cluster egc, exfoliatin A, B, and D) and their correlation with disease severity in 34 patients with AD, have shown that patients with a moderate SCORAD were more likely to be colonized by enterotoxin B-positive S.aureus (P = 0.027) and no virulence factor was significantly associated with a severe SCORAD (16). We are not sure exactly the reason of the lack of MRSA in patients with severe SCORAD, but certain reasons can be suggested. There were only a few patients with MRSA and the number of patients was not similar in each level of severity. We did not match for age in different groups of severity. One retrospective study in children with atopic dermatitis has shown that the prevalence of MRSA is increased in children older than 5 years (28). Other research without these limitations may help to clarify the significance of this abnormal finding.
In conclusion, our data shows lower rate of S.aureus colonization in AD patients but a similar rate of MRSA colonization in comparison with former studies. In our study the patients with moderate SCORAD had a higher rate of MRSA colonization. We did not have a control group in our study and also do not know about S.aureus colonization rate in our general population. More research with a control group and larger sample sizes would be supportive for identification of the exact relationship between MR pattern and SCORAD index in atopic dermatitis.
Cho SH, Strickland I, Tomkinson A, Fehringer AP, Gelfand EW, Leung DY. Preferential binding of Staphylococcus aureus to skin sites of Th2-mediated inflammation in a murine model. J Invest Dermatol. 2001; 116 (5) : 658 -63 [DOI][PubMed]
Guzik TJ, Bzowska M, Kasprowicz A, Czerniawska-Mysik G, Wojcik K, Szmyd D, et al. Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters. Clin Exp Allergy. 2005; 35 (4) : 448 -55 [DOI][PubMed]
Hanifan JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermatol Venereol. 1980; 92 : 44 -7
Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology. 1993; 186 (1) : 23 -31 [PubMed]
Higaki S, Morohashi M, Yamagishi T, Hasegawa Y. Comparative study of staphylococci from the skin of atopic dermatitis patients and from healthy subjects. Int J Dermatol. 1999; 38 (4) : 265 -9 [DOI][PubMed]
Chiu LS, Ho MS, Hsu LY, Tang MB. Prevalence and molecular characteristics of Staphylococcus aureus isolates colonizing patients with atopic dermatitis and their close contacts in Singapore. Br J Dermatol. 2009; 160 (5) : 965 -71 [DOI][PubMed]
Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997; 10 (3) : 505 -20 [PubMed]
Suh LM, Honig PJ, Yan AC. Methicillin-resistant Staphylococcus aureus skin abscesses in a pediatric patient with atopic dermatitis: a case report. Cutis. 2006; 78 (2) : 113 -6 [PubMed]
Ortega-Loayza AG, Diamantis SA, Gilligan P, Morrell DS. Characterization of Staphylococcus aureus cutaneous infections in a pediatric dermatology tertiary health care outpatient facility. J Am Acad Dermatol. 2010; 62 (5) : 804 -11 [DOI][PubMed]
Schlievert PM, Strandberg KL, Lin YC, Peterson ML, Leung DY. Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis. J Allergy Clin Immunol. 2010; 125 (1) : 39 -49 [DOI][PubMed]
Chung HJ, Jeon HS, Sung H, Kim MN, Hong SJ. Epidemiological characteristics of methicillin-resistant Staphylococcus aureus isolates from children with eczematous atopic dermatitis lesions. J Clin Microbiol. 2008; 46 (3) : 991 -5 [DOI][PubMed]
Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009; 123 (5) : e808 -14 [DOI][PubMed]
Breuer K, S HA, Kapp A, Werfel T. Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol. 2002; 147 (1) : 55 -61 [DOI][PubMed]
Williams RE, Gibson AG, Aitchison TC, Lever R, Mackie RM. Assessment of a contact-plate sampling technique and subsequent quantitative bacterial studies in atopic dermatitis. Br J Dermatol. 1990; 123 (4) : 493 -501 [DOI][PubMed]
Kedzierska A, Kapinska-Mrowiecka M, Czubak-Macugowska M, Wojcik K, Kedzierska J. Susceptibility testing and resistance phenotype detection in Staphylococcus aureus strains isolated from patients with atopic dermatitis, with apparent and recurrent skin colonization. Br J Dermatol. 2008; 159 (6) : 1290 -9 [DOI][PubMed]
Hon KL, Lam MC, Leung TF, Kam WY, Li MC, Ip M, et al. Clinical features associated with nasal Staphylococcus aureus colonisation in Chinese children with moderate-to-severe atopic dermatitis. Ann Acad Med Singapore. 2005; 34 (10) : 602 -5 [PubMed]
Tomi NS, Kranke B, Aberer E. Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and erythroderma, and in healthy control subjects. J Am Acad Dermatol. 2005; 53 (1) : 67 -72 [DOI][PubMed]
Zollner TM, Wichelhaus TA, Hartung A, Von Mallinckrodt C, Wagner TO, Brade V, et al. Colonization with superantigen-producing Staphylococcus aureus is associated with increased severity of atopic dermatitis. Clin Exp Allergy. 2000; 30 (7) : 994 -1000 [DOI][PubMed]
Arkwright PD, Daniel TO, Sanyal D, David TJ, Patel L. Age-related prevalence and antibiotic resistance of pathogenic staphylococci and streptococci in children with infected atopic dermatitis at a single-specialty center. Arch Dermatol. 2002; 138 (7) : 939 -41 [DOI][PubMed]