A study of the prevalence of methicillin-resistant Staphylococcus aureus in dermatology inpatients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of increased morbidity and mortality in debilitated and immunocompromised patients. AIMS AND
OBJECTIVES: To study the prevalence of MRSA among dermatology inpatients and elucidate its predisposing factors and antibiotic sensitivity pattern.
MATERIALS AND METHODS: This prospective study involved all the inpatients in the dermatology ward with suspected bacterial infections, both primary and secondary. Gram's stain, pus culture, and antibiotic sensitivity were the main tests done.
RESULTS: There were 61 patients in this study, with 36 males (59%) and 25 females (41%). The age group maximally affected was 41-50 years (21.6%). Vesiculobullous disorders (22, 36.1%) and eczemas (16, 26.2%) were the commonest dermatoses with secondary infection. Extremities (72.1%) and the trunk (26.2%) were the commonest sites involved. Diabetes mellitus (DM) was the commonest systemic illness (11.5%). Staphylococcus aureus was the commonest isolate, grown in 52 patients (85.2%) of whom 16 (30.80%) were MRSA positive. MRSA constituted 22.2% of the total bacterial isolates. All the MRSA isolates (100%) were resistant to cloxacillin and oxacillin, while all the isolates (100%) were sensitive to vancomycin and linezolid.
CONCLUSIONS: The prevalence of MRSA in this study was high. It was most commonly seen in patients with vesiculobullous disorders. A high sensitivity of MRSA was found to amikacin. There was no relation between prolonged antibiotic therapy and MRSA in this study.

INTRODUCTION

Methicillin resistant Staphylococcus aureus (MRSA) is a pathogen that is causing serious concern all over the world due to its ability to cause morbidity and mortality among chronic, debilitated and immunocompromised patients.[1] MRSA is classified into community-acquired MRSA (CAMRSA) and hospital-acquired MRSA (HAMRSA). CAMRSA is defined as a bacterial isolate seen in the outpatient setting or within 48 hours of hospitalization.[2] HAMRSA is attributed to nosocomial infection seen in patients with prolonged stay in hospitals such as intensive care units (ICU's), patients with indwelling devices, hemo- or peritoneal dialysis, mechanical ventilation and tracheostomy.[3] MRSA can cause infections ranging from simple furuncles to life-threatening necrotizing fasciitis and pyomyositis.[4] Methicillin resistance in Staphylococcus aureus (SA) is due to the gene mecA that is responsible for the β-lactam resistance by encoding the methicillin-resistant penicillin-binding protein PBP2a.[4] The virulence of MRSA is due to the Panton-Valentine leukocidin factor which is a dermonecrotic and leukocidal toxin.[4] MRSA isolates were frequently encountered among inpatients at our tertiary care institute. We therefore decided to conduct this study to determine the prevalence of MRSA infection among our inpatients as the primary objective and to elucidate the predisposing factors and antibiotic sensitivity pattern of MRSA as the secondary objectives.

MATERIALS AND METHODS

This was a prospective, descriptive, one year study conducted at the department of dermatology and venereology of our tertiary care referral hospital. The study population included all dermatology inpatients with suspected bacterial infections, both primary and secondary. All the patients included in the study were subjected to a detailed history and examination. Age, sex, duration of illness, and comorbidities such as DM were the main demographic data collected. The nature and onset of skin lesions, presence of any predisposing factors, and previous history of treatment with antibiotics or steroids were the other data collected. Detailed general, systemic, and dermatological examinations were made in each case. Routine blood and urine tests, liver function tests, renal function tests, blood glucose levels, and enzyme-linked immunosorbent assay for human immunodeficiency virus (HIV) were done in all patients. The skin lesions were thoroughly cleaned with sterile normal saline and pus samples were drawn with a sterile swab for gram stain, pus culture and sensitivity. The specimens were analyzed in the microbiology department of the institute. A direct colony suspension equivalent to 0.5 McFarland standard were inoculated in Mueller Hinton agar plate, incorporated with oxacillin, methicillin, nafcillin, and vancomycin, supplemented with 2% sodium chloride and incubated at 37°C for 24 h. Staphylococcus aureus colonies were identified by a smooth, convex, shiny and opaque appearance with a golden yellow pigment, as well as coagulase positivity, mannitol fermentation, and production of phosphatase. MRSA was defined as an isolate having a minimum inhibitory concentration (MIC) of >4 μg of oxacillin per mL, while a methicillin-sensitive Staphylococcus aureus (MSSA) isolate was defined as having a MIC of <2 μg of oxacillin per mL.[5] Samples showing moderate to heavy growth of MRSA were included in the study. Samples showing mild growth were repeated, and if no growth was seen in the repeat sample, the results were interpreted as negative. The data collected above was recorded in a standard proforma and were analyzed in terms of descriptive statistics. To elucidate the associations and comparisons between the various parameters, the Chi-square test was employed as nonparametric test. For all statistical evaluations, a probability value of <0.05 was considered significant. Permission to conduct the study was accorded by the ethical committee of the institute.

Disc showing methicillin-resistant Staphylococcus aureus resistant to oxacillin and sensitive to vancomycin

Crusted plaque of pemphigus with positive methicillin-resistant Staphylococcus aureus culture

RESULTS

There were a total of 61 patients in this study (n = 61). There were 36 males (59%) and 25 females (41%), the male/female ratio being 1.44:1. The age group 41-50 accounted for the maximum number of cases (21.6%), the youngest being seven years and the oldest 84 years. The mean age was 45.5 years. Home makers (31.1%), manual workers (21.3%), and skilled workers (18.03%) accounted for the maximum number of cases. Twenty-two patients (36.1%) had duration of skin lesions less than two weeks. A total of 16 patients (26.2%) gave a history of antibiotic use within the previous six weeks, while 13 patients (21.3%) gave history of immunosuppressive therapy, mainly systemic steroids. DM was the commonest systemic illness accounting for seven cases (11.5%). Vesiculobullous disorders comprised the maximum number of cases, 22 (36.1%), followed by eczemas, 16 (26.2%). The various dermatoses with bacterial infection are given in Table 1. Primary bacterial infections accounted for two cases (3.28%), while secondary bacterial infections accounted for 59 cases (96.72%). The two cases of primary pyodermas, (3.28%) were CAMRSA, while all the rest were HAMRSA. The extremities (44 cases, 72.1%), followed by the trunk (16, 26.2%), were the commonest sites involved. None of the patients were HIV positive. A total of 52 cases (85.25%) showed gram-positive cocci. The various bacterial isolates in culture are given in Table 2. SA was the most common isolate grown in culture accounting for 52 cases (85.25%), of which 36 (69.2%) were MSSA, while 16 (30.8%) were MRSA. MRSA accounted for 22.2% of the total bacterial isolates. MRSA was most commonly isolated from vesiculobullous disorders, seven cases (31.8%). A total of 86.1% of the MSSA were resistant to penicillin and 100% sensitive to cloxacillin, while all the MRSA isolates (100%) were resistant to penicillin, cloxacillin, and oxacillin. All the MRSA isolates (100%) were sensitive to vancomycin and linezolid. The details of the patients in which MRSA were isolated are given in Table 3.

Table 1

Various dermatoses with bacterial infection in the study population (n=61)

Table 2

Bacterial isolates in culture*

Table 3

Clinical features and antibiotic sensitivity of patients with methicillin-resistant Staphylococcus aureus (n=16)

DISCUSSION

Sepsis in dermatology inpatients is a dreaded complication especially in patients with pemphigus and toxic epidermal necrolysis (TEN) and contributes significantly to mortality.[6] The present study comprised 61 patients with primary and secondary bacterial infections, accounting for 9.3% of the total new dermatology inpatients in the study period, admitted in a tertiary care referral center. In the study by Sharma et al., and in the study by Asati et al., bacterial infections in the wards accounted for 6.6% and 4.65%, respectively.[78]

There was a male preponderance in this study with a male/female ratio of 1.44:1. The male preponderance in this study could be due to the fact that the majority of the cases in this study were manual and skilled workers who are more prone to trauma, as well as the risk of close physical contact amongst themselves. The role of close physical contact in MRSA acquisition has been presented in previous studies.[9] Male preponderance has been found in other Indian studies also.[710] However, in the study by Asati et al.,[8] there was a female preponderance.

In the present study, the maximum number of cases belonged to the 41-50 age group. This is similar to the other Indian studies by Asati et al., Sharma et al., and Malhotra et al.[7810] A total of 36.1% of the cases in the present study had duration of illness less than two weeks duration, which chiefly comprised the primary pyodermas and eczemas, while long duration of illness was seen in the vesiculobullous group. Many studies have shown that the duration of illness was found to correlate with the risk of MRSA infection, especially in cases of autoimmune vesiculobullous disorders.[4] In the present study however, the duration of illness and acquisition of MRSA infection was not statistically significant (P = 0.43).

In the present study, DM was present in 18.8% of the MRSA patients, while in the study by Asati et al., it was 12.5% and in the study by Sharma et al., 33.3%.[78] It is a well-known fact that DM predisposes to sepsis, especially in the chronic-debilitated patient.

Vesiculobullous disorders were the commonest disorder in this study to be secondarily infected with bacteria, similar to other Indian studies.[78101112] Seven cases of autoimmune vesiculobullous disorders, mainly pemphigus and pemphigoid were positive for MRSA culture, even though this was not statistically significant (P = 0.54). In the present study, 10 patients (62.5%) with MRSA infection were on prolonged antibiotic therapy and immunosuppressive therapy, mainly oral corticosteroids, even though this was not statistically significant (P = 0.16). The duration of antibiotic therapy ranged from 2 to 4 weeks. Ampicillin, ciprofloxacin, and azithromycin were the commonest antibiotics used. Majority of the aforementioned cases had autoimmune vesiculobullous disorders. Many studies have shown positive correlation with prolonged antibiotic and corticosteroid therapy with MRSA acquisition.[14]

Analysis of the regional distribution of the lesions in the present study showed that the extremities were the most common sites involved (72.1%). This is similar to the study by Cohen.[4] This is understandable as the extremities are sites that are more prone for trauma and secondary infection.[411] In the present study, 12 patients (75%) with MRSA infection had erosions as the secondary lesions. The risk of MRSA infection with interruption of skin integrity has been highlighted by Begier et al.,[9] especially among patients who are MRSA nasal carriers.

A total of 52 patients in the present study (85.25%) showed presence of gram-positive cocci arranged in clusters and SA were grown in culture in all these cases. Thus, the study showed high correlation between gram stain and pus culture and sensitivity for SA. SA was the most common organism isolated in this study accounting for 52 cases (85.5%). This was much higher compared to the studies by Asati et al., Sharma et al., and Malhotra et al., indicating a very high prevalence of SA among dermatology inpatients at our institute.[7810] In the present study, 69.20% of the SA was MSSA, while 30.8% of the SA was MRSA. MRSA accounted for 22.2% of the total bacterial isolates. The other isolates were Streptococcus, Pseudomonas, and Klebsiella which were also noted in similar Indian studies. However, in the study by Asati et al., MRSA was the commonest isolate (25.9%), while in the study by Malhotra et al., MRSA accounted for 9.84%.[810] International studies show a prevalence of MRSA ranging from 8% to 20%.[4] However, in the study of Patel et al.,[1314] the prevalence of MRSA in outpatients with pyoderma was only 1.4%, indicating that the type of MRSA in dermatology inpatients is predominantly HAMRSA. The present study also showed only two cases with CAMRSA.

The present study and the aforementioned Indian studies showed vesiculobullous disorders as the commonest to be colonized by MRSA. Autoimmune vesiculobullous disorders are chronic disorders requiring prolonged antibiotic and immunosuppressive therapy, predisposing them to MRSA infection.[411] Special topical care is essential for these patients, especially those with pemphigus and TEN, to prevent MRSA infection. Areas such as the nostrils, axillae, perineum, and web spaces are the sites usually showing MRSA colonization. These should be thoroughly cleaned on a daily basis with antibacterial agents like triclosan, chlorhexidine, and other agents.[1516] It is often worthwhile to take nasal swabs for culture in the aforementioned patients at the time of admission, as some of them may be MRSA nasal carriers.[1516] In such patients, it is often the skin erosions that are colonized by MRSA which enter the blood stream to cause pneumonia and septicemia, contributing significantly to the mortality of the patient.

The antibiotic sensitivity pattern of the present study indicated that 87.5% of the MSSA were resistant to penicillin and 100% sensitive to cloxacillin, while all the MRSA strains were resistant to penicillin, cloxacillin, and erythromycin. All the MRSA strains were sensitive to vancomycin and linezolid, while 93.75% were sensitive to amikacin, clindamycin, and rifampicin. This is an interesting finding since amikacin and rifampicin are cheaper and easily available antibiotics than vancomycin or linezolid, and thus can be considered as first-line antibiotic for MRSA in resource poor situations or when the latter is not available. In the present study, the MSSA strains were 100% sensitive to cloxacillin, which is again a cheap, effective, and widely available antibiotic. Similar findings were echoed in the studies by Asati et al., Sharma et al., and Malhotra et al.,[7810] However, in the study by Sharma et al., the sensitivity of MRSA to amikacin was only 41.2%.[7] In the study by Asati et al., MRSA was also sensitive to teicoplanin which was not tested in the present study.[8] The newer antibiotics which are effective against MRSA are tigecycline, ceftobiprole medocaril, daptomycin and uinupristin-dalfopristin, and the newer generation carbapenems.[171819] Interestingly, studies have shown that MRSA and even vancomycin-resistant Staphylococcus aureus may be sensitive to the older generation antibiotics doxycycline and cotrimoxazole.[171819]

This study highlights that prolonged duration of illness, prolonged antibiotic and steroid therapy, and DM were relative risk factors for acquiring MRSA. This study also highlights that MRSA infection is high among dermatology inpatients, especially those with vesiculobullous disorders, since in most situations they are admitted in the general wards, unlike their Western counterparts who are admitted in the burns ward and ICU units. Therefore, admitting our vesiculobullous patients in burns wards and ICU units warrants consideration. This study also highlights the fact that MRSA may respond to relatively cheaper antibiotics like amikacin and rifampicin.

CONCLUSIONS

The present study showed a high prevalence of MRSA (22.2%) in dermatology inpatients. Vesiculobullous disorders were the commonest to be infected by MRSA. All of the MSSA strains were sensitive to cloxacillin. All the strains of MRSA were sensitive to vancomycin and linezolid. A very high percentage of the MRSA were sensitive to amikacin. There was no significant statistical association between prolonged antibiotic or steroid therapy, and the acquisition of MRSA infection in this study.