Abstract: There is a gradual, worldwide increase in the development of resistant bacteria. The presence of resistant species on an ulcer bed has specific ramifications with regard to the risk of their environmental spread, as well as to the healing of the affected ulcer. Objective: The objective of this study was to evaluate the efficacy of accepted infection-control procedures in a clinic for cutaneous ulcers. Main outcome measure: Presence of methicillin-resistant Staphylococcus aureus (MRSA) was the main outcome measure of the study. Methods: Patients with leg ulcers of various etiology were included in the study. Since June of 1999, strict implementation of infection-control procedures, according to the United States Centers for Disease Control and Prevention (CDC) guidelines valid at that time, have been carried out in the Out-Patient Clinic for Leg Ulcers of Soroka University Medical Center in Beer-Sheba, Israel. Up to June of 1999, the infection control policy had been rather inconsistent. Two groups of patients were included. The first group included 34 patients, treated from January, 1996, to December, 1998; the second group included 83 patients, treated from January, 2000, to December, 2002. Swabs for bacterial cultures were taken from the ulcer bed from each patient at 2- to 4-week intervals. We compared the two groups with respect to number of patients with positive MRSA isolation, time until MRSA isolation, and presence of risk factors for colonization of MRSA. Results: In the first group (1996–1998), 5 of 34 patients (14.7%) were contaminated with MRSA during their visits to the clinic. In these five patients the mean time from their visit until MRSA isolation was 21 months. In the second group (2000–2002), in 7 of 83 patients (8.4%) were contaminated with MRSA during their visits to the clinic. In these seven patients the mean time from their visit until MRSA isolation was 13.2 months. No statistically significant differences were identified when comparing risk factors for MRSA colonization between these two groups.The relative reduction in the number of patients with positive isolation of MRSA and in the time until its isolation was not found to be statistically significant. Conclusion: Strict implementation of infection-control guidelines is a reasonable and desirable procedure in the treatment of patients with leg ulcers. It may reduce transmission rate of pathogenic bacteria from one patient to another. Further research studies with larger populations of patients are required. Use of these guidelines is a basic element of appropriate and reasonable treatment in patients with cutaneous ulcers.

Introduction

During the last 20 years, methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial worldwide pathogen.[1–5] The acquired resistance of S. aureus strains is not limited to methicillin. S. aureus strains, including MRSA, acquire resistance against other antibiotics, such as gentamicin, ciprofloxacin, fusidic acid, mupirocin, and vancomycin.[6–14] Subsequently, infections that until recently could be dealt with by using traditional antibiotics have become uncontrolled and unresponsive to conventional therapeutic regimens.

The selection of resistant organisms has certain unique aspects when dealing with cutaneous ulcers due to the following causes: 1) Wound beds serve as an optimal breeding ground for pathogenic bacteria; 2) Secretions from these ulcers further increase the risk of environmental spread; and 3) Administration of antibiotics is relatively frequent among patients with cutaneous ulcers, which subsequently leads to the selection of resistant strains.

The presence of cutaneous ulcers is indeed a well-established risk factor for colonization and a prolonged carriage of MRSA.[15–18] Significant risk factors associated with MRSA colonization are hospitalization, admission to intensive care units, antibiotic treatment, and nursing home residence. Additional risk factors for MRSA colonization are old age, male gender, significant disability or immobilization, steroid therapy, immunosuppression or immunosuppressive therapy, diabetes, presence of catheters/tubes, extensive skin disease, surgery, and malnutrition.[15–23]

In general, it is somewhat complicated to compare the prevalence of MRSA in patients with leg ulcers between different clinics/medical centers, since the data are subject to many variables. The prevalence depends on whether the patients are embulatory or hospitalized; whether they are enrolled from a general dermatology clinic or a clinic that specially focuses on treating leg ulcers; and the underlying causes of the ulcers (e.g., percentage of diabetic or pressure ulcers). Thus, the reported range is wide. Trividic, et al.,[15] reported positive isolation of MRSA in 53 of 4,579 (1.1%) patients who were hospitalized in a dermatolgy department during 1997 to 1998; 34 of the 53 patients presented with cutaneous ulcers. In 2001, Roghmann, et al.,[18] reported positive isolation of MRSA in 166 of 545 (30%) patients hospitalized between 1990 to 1995 with chronic ulcers consisting mainly of pressure ulcers. The prevalence of MRSA also depends on the overall prevalence of Staphylococcus strains and their subtypes in certain geographical areas. The use of infection-control procedures may also affect the prevalence, as discussed in the present article.

In June of 1999, strict implementation of infection-control guidelines (detailed below) were carried out in the Out-Patient Clinic for Cutaneous Ulcers at the Soroka University Medical Center in Beer-Sheba, Israel. Up to that point, the infection control policy had been rather inconsistent. The objective was to evaluate the efficacy of accepted infection-control procedures in our clinic.

Methods

Study design. The study was designed as a program evaluation, comparing two patient groups enrolled before and after implementing infection-control procedures.

Main outcome measure. The main outcome measure was the presence of MRSA. The presence of MRSA reflects the transmission rate of bacteria between patients. Patients were regarded as contaminated by MRSA if the organism was isolated at least once at our clinic as of the second visit (see exclusion criteria).

Colonization vs. infection. Identifying an ulcer as infected was based on the currently accepted definition,[24,25] i.e., the presence of erysipelas or cellulitis manifested by systemic signs (fever) and/or local signs (warmth, redness, swelling), or the presence of purulent secretions on the ulcer bed.

Bacterial cultures. Swabs for bacterial cultures were taken from the ulcer bed from each patient at 2- to 4-week intervals. Swabs were immediately placed into a modified Stuart medium and processed according to established bacteriological practices.

Infection-control guidelines. Since June of 1999, infection-control procedures have been strictly implemented in the Out-Patient Clinic for Cutaneous Ulcers. The procedures used are based on the United States Centers for Disease Control and Prevention (CDC) guidelines that were valid at that time[26–28] together with the accepted recommendations of leading textbooks in the field,[29–31] as detailed below:

Hand hygiene. Hand washing is carried out by medical staff as well as the treated patients, according to the guidelines presented by the Association for Professionals in Infection Control and Epidemiology.[28] The hand washing regimen is as follows: Washing the hands is done under running water; 3 to 5mL of a cleaning agent containing four percent chlorhexidine is applied and distributed completely over the hands; hands are rubbed vigorously for approximately 15 seconds; hands are thoroughly rinsed to remove residual soap and then dried. Alternatively, an alcohol-based hand-rub solution containing 70-percent alcohol and 0.5-percent chlorhexidine can be used. Note that the latter is currently considered as a better disinfecting method compared to hand washing.[32,33]

Use of gloves. All medical staff are instructed to wear gloves while treating each patient. A new pair of gloves is used when applying the new dressing.

Avoiding environmental spread. All medical staff and treated patients are instructed to avoid the unnecessary (as far as possible) touching of objects, furniture, or surfaces of the treating room.[29] Patients are instructed not to place a bare foot on the floor but on a stool covered by a clean sheet (Figure 1). Documentation (recording) and writing in the patient’s medical chart are done only after taking off the gloves and washing hands.

Figure 1

The treated foot is placed on a clean sheet.

Waste. Waste, such as a used dressing that has been removed from the ulcer, is transferred directly to a plastic bag placed near the patient (Figure 2). Extreme care is taken to make sure that used dressings do not come into contact with the floor.

Figure 2

Used dressings are transferred to a plastic bag.

Cleaning and disinfecting. Between patients, the treated area and adjacent surfaces are cleaned with soap, followed by application of antiseptic solution (containing 70% alcohol and 0.5% chlorhexidine).

After treating an ulcer suspected of being infected by a resistant strain or a heavily secreting ulcer, the treatment room is cleaned thoroughly with soap, followed by sodium hypochlorite solution with free available chlorine at 500ppm achieved by dilution of 1:100 of household bleach.

Patients are instructed to follow the relevant sections of the above-mentioned guidelines (e.g., handwashing, appropriate disposal of used dressings) while treating ulcers at home.[34]

Patients. Inclusion criteria. Patients treated in the Out-Patient Clinic for Leg Ulcers of Soroka University Medical Center, Beer-Sheba, from 1996 to 2002, who had visited the clinic three times or more were included. The patients had leg ulcers of various etiologies, as detailed in Tables 1 and 2.




Patients were divided into two groups. The first group (group A) included 37 patients treated from January, 1996, to December, 1998 (follow up until March, 1999). The second group (group B) included 96 patients treated from January, 2000, to December, 2002 (follow up until March 2003).

Exclusion criteria. Patients were excluded from the study if there was documentation of positive isolation of MRSA from the ulcers before arrival to the clinic or there was positive isolation of MRSA in the first visit to the clinic, indicating another source of contamination. Subsequently, three patients were excluded from group A and 13 from group B.

The two main parameters compared between the two groups were the number of patients with positive isolation of MRSA and the time until MRSA (if positive) was identified from the patient’s first visit.

Medical data. Medical data were collected retrospectively from the medical charts of the clinic, the patients’ medical charts from family physician clinics, and the hospitalization files.

The required data included documentation of isolation of positive MRSA before arrival to the clinic and the presence of risk factors for colonization of MRSA, detailed in the introduction section and in Table 3.



Based on the available data in the literature,[15–23] we implemented the following criteria in the assessment of risk factors:

1. Days of hospitalization were calculated 12 months prior to MRSA isolation. If MRSA was not isolated, days of hospitalization or days of antibiotic treatment were calculated 12 and 6 months, respectively, prior to the patient’s last visit to the clinic.

2. The total number of days of systemic antibiotic treatment were calculated both for the overall antibiotic treatment and separately for each antibiotic subgroup, which included penicillins, cephalosporins, fluoroquinolones, tetracyclines, macrolides, metronidazole, clindamycin, and fusidic acid. A similar calculation was used for days of treatment of topical antibiotics, overall topical antibiotic treatment, and separately for each subgroup, which included gentamicin, mupirocin, chloramphenicol, and fusidic acid.

Statistical analysis. Presence of positive MRSA and time until its isolation were compared between group A (before implementation of infection-control guidelines) and group B (for which infection-control guidelines were strictly implemented). In addition, risk factors for MRSA colonization were compared between the two groups. We used the t-test for comparison of continous variables, while the c2 test (Fisher’s exact test when appropriate) was used for comparison of categorial variables.

Results

The present study refers to 117 patients treated in the Out-Patient Clinic for Cutaneous Ulcers of Soroka University Medical Center. Thirty-four patients were treated between 1996 and 1998 (group A): 17 women, 17 men. Mean age was 61.7±12.3 years (range: 39–84). Eighty-three patients were treated between 2000 and 2002 (group B): 50 women, 33 men. Mean age was 65.2±13.3 years (range: 22–88).

Risk factors for colonization of MRSA in the two groups are presented in Table 3. Apart from a borderline finding regarding a relatively older age group of group B (p=0.06), no statistically significant differences were identified between the two groups of patients.

Five of 34 patients (14.7%) in group A were contaminated with MRSA during their visits in the clinic, compared to 7 of 83 patients (8.4%) in group B. The p value (Fisher’s exact test) was 0.24. The mean time from a patient’s first visit until positive identification of MRSA was 21±9.1 months in group A (range: 7–32) and 13.3±13.3 in group B (range: 1–26). p value was 0.3 (t-test).

In two of the 12 patients (of both groups) contaminated with MRSA during their visits to the clinic, there was clinical evidence of infection by the time the culture samples were taken. One patient had cellulitis, and another patient exhibited purulent discharge on the ulcer bed.

In a follow-up until December 2003, the ulcers healed in 4 (33.3%) of the 12 patients who were contaminated with MRSA. In seven patients (58.3%), the ulcers did not heal; one patient (8.3%) died and another patient (8.3%) had moved to another location. In 105 patients (from group A and group B) who were not contaminated with MRSA during their visits to the clinic, the results were as follows: In 78 patients (74.2%), the ulcers healed; in 13 patients (12.3%), the ulcers did not heal. Twelve patients (11.4%) deceased, and two patients (1.9%) moved to another location.

Conclusions

Very few well-controlled studies have been carried out to confirm the efficacy of the accepted infection-control guidelines and have shown that implementing infection-control procedures indeed reduced the rate of infections in medical facilities.[35–39] To the best of our knowledge, this is the first study that has assessed the efficacy of infection control guidelines in an out-patient clinic for chronic cutaneous ulcers.

Comparing group A to group B, a nonsignificant reduction in isolation of MRSA was observed. One should take into account several factors that may have had an effect upon the results presented:

1. There has been a gradual overall increase in the presence of MRSA of recent years, as is reflected in the literature.[1–5] In addition, our study revealed an ever-increasing number of patients identified as contaminated by MRSA before arrival to our clinic. Unfortunately, no accurate updated data regarding the prevalence of MRSA could be obtained from neighboring out-patient clinics in the Soroka University Medical Center that treat patients with chronic cutaneous ulcers.

2. Another issue that should be considered is the increase in the number of patients treated in our clinic: 96 patients between 2000 and 2002 compared to 37 patients between 1996 and 1998. Note that in respect to the change in the number of patients, the increase in the possible interactions between treated patients and the subsequent risk of spreading infection rises in square ratio, i.e., on any given day, each patient may contaminate or be contaminated by any one of the other patients; the formula being n x (n-1) whereby n = number of patients. Hence, the reduction in the number of patients with positive isolation of MRSA is encouraging.

Comparing group A to group B in respect to the time until MRSA was identified (from the patient’s first visit), we found a relative, but not statistically significant, reduction. This reduction may seem paradoxical: In the cases in which the infection-control guidelines were implemented, one would have expected a longer time to pass until contamination was evident. A possible explanation for this finding could be that some of the patients may have been carriers of MRSA prior to arrival to our clinic but were not identified in their first visits to the clinic (i.e., false negative results as to isolation of MRSA).

We suggest that strict implementation of infection-control guidelines may reduce the transmission rate of pathogenic bacteria from one patient to another. Moreover, the use of these guidelines also constitutes a basic element of appropriate and reasonable treatment in patients with cutaneous ulcers.

Any cutaneous ulcer is, in fact, a breeding ground for the development and the spreading of resistant species. Immediate measures should be taken to heal the wound. On the broader scale, every possible effort should be put into the area of wound healing, especially in respect to directing human and financial resources.

Acknowledgment

The authors wish to thank Professor Pablo Yagupsky, Dr. Abraham Borer, and Miss Kristina Hawthorne for their most valuable assistance throughout the course of this project.