Pressure Ulcers Colonized by MRSA as a Reservoir and Risk for MRSA Bacteremia in Patients at a Brazilian University Hospital

  Abstract: Pressure ulcers (PU) are a major reservoir of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. The objectives of this study were to estimate the prevalence of MRSA colonization in PU of hospitalized patients with Stage II or higher PU, to identify risk factors for colonization of these wounds, and to ascertain whether MRSA colonization of PU increases the risk of MRSA bacteremia. Methods. This study was conducted at the Clinical Hospital of Federal University of Uberlandia, MG, Brazil. A prospective cohort study of 145 patients with Stage II or higher PU, colonized or not with MRSA, was conducted over 21 months. Infected ulcers were defined for clinical signs and for positive evaluation of smears of the wound by the ratio of polymorphonuclears to epithelial cells of ≥ 2:1, after Giemsa staining. Results. Sixty-three (43.5%) MRSA colonized PU patients were identified, but none of the risk factors analyzed were independently associated with MRSA colonization. Among the patients with positive blood cultures and MRSA colonized PU, the odds ratio for MRSA bacteremia (OR = 19.0, 95% CI = 2.4–151.1, P < 0.001) and mortality rate (OR = 21.9, 95% CI = 1.23–391.5, P = 0.002), were high. Independent risk factors for MRSA bacteremia were: ≥ 2 underlying disease (OR = 6.26, 95% CI = 1.01–39.1, P = 0.05) and prior MRSA infected PU (OR = 12.75, 95% CI=1.22–132.9, P = 0.03). Conclusion. The present study identifies MRSA colonized PU patients as a potential epidemiologic reservoir for this organism and a high-risk for MRSA bacteremia, which contributes to prolonged hospitalization and poor prognosis.

Introduction

  Pressure ulcers (PU) develop mainly as a consequence of continued skin pressure over bony prominences. Pressure ulcers lead to the disruption of skin integrity, local tissue ischemia, and necrosis. The development of PU not only lengthens a patient’s hospital stay, but also increases nurses’ workload and healthcare costs.¹ Prevalence is particularly high in critical care units (approximately 22%) and incidence ranges from 8%–40%.²   Methicillin-resistant Staphylococcus aureus (MRSA) has increased in relative frequency among isolates from nosocomial infections.³S. aureus and the phenotype MRSA are commonly recovered from PU cultures,⁴ besides being the common cause of hospital-acquired bloodstream, surgical site, and respiratory tract infections.^3,5 Pressure ulcers are, therefore, reservoirs for these organisms and may impact nosocomial infections.⁵ Some reports show the importance of PU as potential sources of bacteremia in hospitalized patients; S. aureus is the most commonly isolated organism in these infections.^6,7   Standard prevention of MRSA transmission is the same as for all S. aureus strains and includes good hygiene, proper hand washing, and appropriate care of skin wounds or infections, all of which reduce or prevent transmission.⁸ Nurses’ hands are more easily contaminated since patients with PU are strongly associated with longer hospital stays1 and require more intensive care for their wound dressings.⁹ Eliminating colonization is a possible strategy for preventing infection since MRSA colonization generally precedes MRSA infection.^4,5,10   The objectives of this study were to estimate the prevalence of MRSA colonization in PU of hospitalized patients with Stage II or higher PU, to identify risk factors for colonization of these wounds, and to ascertain whether MRSA colonization of PU increases the risk of MRSA bacteremia in a Brazilian university hospital.

Materials and Methods

  Setting and study design. This study was conducted at the Clinical Hospital of Federal University of Uberlandia, MG, Brazil, a tertiary teaching hospital with 510 beds. Two retrospective cohort studies were concurrently performed: the first group included patients who had Stage II or higher PU; methicillin-resistant S. aureus colonization was the primary outcome variable. The second cohort study was performed to estimate the risk of MRSA bacteremia in patients colonized with MRSA detected during the studies periods (April–December 2005 and August 2009–July 2010). The medical records of PU patients identified by active surveillance, were reviewed for demographic and risk factor data. Infected ulcers were defined for signs and symptoms of infection, such as pain, erythema, edema, heat, purulent exudates with concurrent inflammation, delayed healing, discoloration of granulation tissue, friable granulation tissue, pocketing at the base of the wound, foul odor, and wound breakdown.¹¹ In addition, positive evaluation was considered when a smear of the PU demonstrated a ratio of polymorphonuclears to squamous epithelial cells of ≥ 2:1 after Giesma staining.¹² Bacteremia was defined as the presence of viable bacteria in the blood¹³; the first MRSA bacteremia episode seen in a patient was taken into consideration. MRSA was considered to be nosocomially acquired if it was detected from a patient (ulcer and blood) who had been in the hospital unit for at least 48 hours.   Specimen collection. Prior PU cleaning was performed with sterile, warm saline (≈ 37.5˚C) and aseptic technique under irrigation pressure with a syringe (20 mL) and needle (25 x 8: 21-gauge).¹⁴ Afterward, a sterile swab moistened with saline solution was rotated over a 1-cm square of granulation tissue with sufficient pressure to force fluid from the wound tissue.¹⁵   Microbiological techniques. The swab was inoculated in Mannitol salt agar, and the S. aureus strain was identified as coagulase-positive by a classic technique routinely applied in the Federal University of Uberlandia Microbiology Laboratory. Hemoculture was performed by inoculating 5 mL–10 mL of blood into a flask of the commercial automated system Bactec/Alert® (Vitek Sistem, Organon Teknika Corp).   Antimicrobial susceptibility test. Susceptibility to oxacillin by gel diffusion techniques (LB, Laborclin Ltda, Brazil) was determined on Muller-Hinton Agar (BD, Becton Dickinson and Company, France) according to the Clinical and Laboratory Standards Institute’s recommendations.¹⁶   Ethical approval. The study was approved by the Research Ethics Committee of the Federal University of Uberlandia, Uberlandia, MG, Brazil (Approvals: 118/05, 370/09). Informed consent was obtained from each patient. To ensure anonymity, personals details were removed from copies of the records.

Statistical Analysis

  Statistical analyses were prepared using GraphPad Prism version 4 (GraphPad Software, San Diego, CA) for univariate analysis and Bioestat 5.0 (Belém, PA, Brazil) for multivariable analysis. To determine the risk factors, the control and case groups were compared using the Student’s t test for continuous data, and the Fisher exact test or chi-square test for categorical data, when appropriate. P ≤ 0.05 was considered significant.

Results

  In total, 145 patients with Stage II or higher PU were investigated in this study. The group was mainly comprised of men (57.2%, 83/145), and the average age was 61 years (range, 20 to 101 years). These patients were hospitalized for an average of 69.6 days. Almost two-thirds of the patients were hospitalized for clinical problems (60.1%, 88/145). Heart disease (67.6%, 98/145) and diabetes mellitus (30.3%, 44/145) were the most common underlying diseases. Two or more invasive devices (70.3%, 102/145) and prior antibiotic treatment (mainly third or fourth generation cephalosporins [36.6%, 53/145]), and ≥ 2 different classes (56.5%, 82/145) were also common in this group. Furthermore, 43.5% (63/145) of patients were MRSA colonized with PU, and the presence of infected PU was observed in 27.6% of patients (40/145). A total of 8.3% (12/145) of the study patients developed MRSA bacteremia, and the overall mortality rate of patients was 42.1% (61/145) during the study period. Table 1 summarizes the patients’ characteristics.   Variables identified by univariate analysis as significant risk factors associated with MRSA colonized PU patients were: length of hospital stay ≥ 30 days (OR = 3.0, CI 95% = 1.45–6.3, P < 0.01), prior antibiotic treatment (OR = 5.2, CI 95% = 2.34–11.7, P < 0.001), and clinical infection (OR = 3.49, CI 95% = 1.56–7.92, P = 0.001) (Table 2). Table 3 shows that none of these were independent risk factors by multivariate analysis.   Table 4 compares the patients with MRSA colonization of PU with and without MRSA bacteremia. Among the patients with positive blood cultures, the odds ratio of MRSA bacteremia in the group with colonization was high and statistically significant (OR = 19.0, 95% CI = 2.4–151.1, P < 0.001), as was the mortality rate (OR = 21.9, 95% CI = 1.2–391.5, P = 0.002).   Among the patients with MRSA bacteremia and PU colonization aged ≥ 60 years (OR = 6.1, 95% CI = 1.2–30.6, P = 0.02), respiratory disease (OR = 4.55, 95% CI = 1.2–16.9, P = 0.01), ≥ 2 underlying disease (OR = 5.5, 95% CI = 1.32–22.93, P = 0.02), central venous catheter use (OR = 5.05, 95% CI = 1.2–21.0, P = 0.02), and infected PU (OR = 8.34, 95% CI = 1.1–69.6, P = 0.04) were significant risk factors by univariate analysis (Table 5). After adjustment for confounding was completed, only ≥ 2 underlying disease (OR = 6.26, 95% CI = 1.04–39.1, P = 0.04) and prior MRSA infected PU (OR = 12.75, 95% CI = 1.22–132.9, P = 0.03) were independent risk factors associated with MRSA bacteremia (Table 6).

Discussion

  Risk factors for acquisition of MRSA in hospitalized patients are well known and include: advanced age, admission to intensive care, previous hospitalization, invasive procedures, and recent antibiotics. Multiple case-control studies have analyzed the risk factors associated with MRSA infection or colonization, and demonstrated that antibiotic exposure and cephalosporin are risk factors for infection with MRSA.^17–19 In the present study, patients who had Stage II or higher PU presented with these characteristics, including prolonged hospitalization (average of 69.6 days), ≥ 2 invasive devices (70.3%, 102/145), prior antibiotic treatment mainly by third or fourth generation cephalosporins (36.6%, 53/145), and ≥ 2 different antimicrobial classes (56.5%, 82/145).   It has been shown that nasal carriers of S. aureus have an increased risk of acquiring an infection with this pathogen in general hospital populations.²⁰S. aureus colonizes the anterior nares of 20% to 30% of patients at any given time, and there is evidence these asymptomatic nasal carriers of S. aureus are at increased risk of developing serious staphylococcal infections, mainly among patients admitted to intensive care units,²¹ surgical patients, patients on hemodialysis or continuous peritoneal dialysis, patients with cirrhosis, and after liver transplantation.²²   Pressure ulcers are also frequently colonized with several different organisms. Cultures yield a polymicrobial flora of gram-positive and gram-negative aerobic and anaerobic species. S. aureus is among the most frequently isolated organisms.²³ Colonization with MRSA occurs frequently in institutions with endemic MRSA.²⁴ In the authors’ hospital, studies have reported a high endemic prevalence rate of MRSA colonization significantly associated with the following risk factors: length of hospitalization, prior use of antibiotics, age, and several underlying illnesses.^25,26 In the present study, almost half (43.5%, 63/145) of the patients presented with MRSA colonization of their PU. In addition, hospital stays ≥ 30 days (OR = 3.0, CI 95% = 1.45–6.3, P < 0.01), prior use of antibiotics (OR = 5.2, CI 95% = 2.34–11.70, P < 0.001), and clinical infection (OR = 3.49, CI 95% = 1.56–7.92, P = 0.001), were significant risk factors under univariate analysis, but none of these was an independent risk factor for MRSA colonization of PU.   Early identification of patients colonized with MRSA and subsequent prevention of patient-to-patient spread through infection control measures are believed to be potent interventions to control MRSA.²⁷ A wound, particularly the PU, creates a reservoir of these organisms that may impact other nosocomial infections and require infection prevention and meticulous control measures to prevent it from spreading to other patients.⁵ The presence of MRSA in a wound should be of concern in healthcare, and the nurse should manage the wound by adhering to the principles of asepsis.²⁷ Considering the nursing dependence of patients with a Stage II or higher PU, which includes regular dressing changes and usually prolonged hospitalization, as seen in the present series, healthcare workers’ hands are easily contaminated during the process of caregiving. Thus, precautions are needed in order to prevent nosocomial MRSA infections.⁹   Pressure ulcers serve as a reservoir for MRSA in hospitals, and MRSA is commonly recovered from these ulcers.¹¹ Based on prior studies of MRSA colonization, the association of PU with bacteremia is well established but is probably underestimated, and few studies have addressed this problem systematically.^4,6 Furthermore, the magnitude of the risk of MRSA bacteremia in these patients also is unknown, and data must be made available for large cohorts of patients.4 In the present study, the prevalence of patients with MRSA colonization of a PU was high (43.5%), and this colonization preceded MRSA bacteremia; the authors found the odds ratio of 19.0 (P < 0.001) when compared to patients with PU but without MRSA colonization. The present results also showed that age ≥ 60 years, respiratory diseases, ≥ 2 underlying diseases, central venous catheter use, and infected PU were significant risk factors for MRSA bacteremia in PU MRSA colonized patients. However, under multivariate analyses, only the presence of ≥ 2 underlying illnesses (OR = 6.26, CI 95% = 1.04–39.1, P = 0.04) and prior MRSA infected wound (OR = 12.75, CI 95% = 1.22–132.9, P = 0.03) were independent risk factors associated with MRSA bacteremia.   Generally, patients predisposed to PU are at higher risk of morbidity, costs, and mortality.^1,6 The development of an in-hospital PU was associated with greater risk of death over a 1-year period.²⁹ The relationship between bacteremia and PU was associated with a mortality rate of 50% and has been found to exhibit the high incidence of S. aureus in these infections.^6,7 Bacteremia was documented in 16 (76%) of 21 patients with sepsis attributed to PU and 47.6% of these patients died; eight of whom died despite receiving appropriate antibiotics.³⁰ The present findings reemphasize this poor prognosis, with 58.3% of death in patients with MRSA bacteremia following MRSA colonization of PU.   There are several potential limitations of the present study that should be mentioned. First, because all study patients were hospitalized at a single tertiary hospital, the present results may not be generalized to other institutions. Another limitation of this study was that information regarding the management of the condition and the severity of underline illness (eg, the APACHE II score) was unavailable, and the authors had a relatively small sample size, thus reducing statistical power and the ability to study subsets of patients. However, an additional review demonstrated that this group did not have a significant number of MRSA infections that would have changed the study’s outcomes.

Conclusion

  The present study shows that Stage II or greater pressure ulcers in these patients were colonized by MRSA with significant ease and represented potential epidemiologic reservoirs of this organism in the authors’ institution. The independent risk factors for MRSA bacteremia in these colonized wounds were greater than or equal to two underlying illness and prior MRSA infected PU by this organism. This cohort study identified MRSA colonized PU patients in an acute setting hospital as a high-risk population for MRSA bacteremia and contributed to prolonged hospital stay and poor prognosis.

References

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Cely Christine Nery Silva Pirett and Iolanda Alves Braga are from Microbiology, Biomedical Sciences Institute of Federal University of Uberlandia and Clinical Hospital of Federal University of Uberlandia; Drs. Ribas and P. Filho are from Microbiology, Biomedical Sciences Institute of Federal University of Uberlandia; and Dr. A. Filho is from Clinical Hospital of Federal University of Uberlandia and Department of Surgery, Faculty of Medicine, Federal University of Uberlandia, Brazil. Address correspondence to: Cely Christine Nery Silva Pirett, MSc Rua Das Cerejeiras, No. 101 Bairro Jaragua Uberlandia, Minas Gerais, CEP 38413-096 celpirett@yahoo.com.br