Advanced Emergency Nursing Journal:
Clinical Management of Skin and Soft Tissue Infections in the Emergency Department of a Suburban Hospital
Winstead, Yvette DNP, CRNP, FNP-BC, MBA, MA, MS; Emmerich, Harry DO; Manning, Mary Lou CRNP, PhD; Winstead, Denita PhD, RN, BSN; Nelson-Bachmann, Patrice MSN, CRNP, FNP-BC; Kornecki, Zbigniew RN, BSN, CEN
Jefferson School of Nursing (Dr Manning), Thomas Jefferson University (Dr Yvette Winstead), Philadelphia, Pennsylvania; Aria Health Care System, Emergency Medicine, Langhorne, Pennsylvania (Drs Yvette Winstead and Emmerich); Johnson & Johnson, Pharmaceutical Development, Spring House, Pennsylvania (Dr Denita Winstead); and Emergency Medicine (Ms Nelson-Bachmann) and Medical Informatics (Ms Kornecki), Aria Health Care System, Philadelphia, Pennsylvania.
Corresponding Author: Yvette Winstead, DNP, CRNP, FNP-BC, MBA, MA, MS, Thomas Jefferson University, Jefferson School of Nursing, Edison Building, 130 South 9th St, Philadelphia, PA 19107 (firstname.lastname@example.org).
The authors would like to thank Dr. Jennifer Bellot, RN, PhD, Dr. Kwame Obeng, PhD, Flourine Winstead, Sherry Winstead, BS, George Winstead, AS, Walter Winstead, III and Joesph Lestochi, BS, for the many hours of consultation.
Skin and soft tissue infections (SSTIs) caused by Staphylococcus aureus are among the most common infections encountered by emergency department (ED) physicians and nurse practitioners. Until recently, clinical management of such infections consisted of incision and drainage and antibiotic therapy. Of concern is the growing prevalence of community-acquired methicillin-resistant S. aureus as the cause of SSTIs, thus requiring a change in clinical evaluation and management. In 2007, the Centers for Disease Control and Prevention issued management guidelines, but research indicates a wide variation in how ED clinicians manage patients. This research project describes the prevalence and clinical management of SSTIs in a suburban hospital's ED.
SKIN AND SOFT TISSUE INFECTIONS (SSTIs) are among the most common infections encountered by emergency physicians and nurse practitioners. Surveys conducted between 1997 and 2005 of office-based physicians, hospital outpatient and emergency departments (EDs) in the United States indicated that visits for SSTIs increased from 8.6 million in 1997 to 14.2 million in 2005, a 65% increase in frequency (Hersh, Chambers, Maselli, & Gonzales, 2008).
Staphylococcus aureus, and to a lesser extent streptococci are the most common causes of SSTIs (Abrahamian, Talan, & Moran, 2008; Frazee et al., 2005). Of growing concern is the increasing prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as a cause of SSTIs (Moran et al., 2006; Pallin et al., 2008). For instance, a recent study conducted in EDs in 11 U.S. cities found that MRSA was isolated from 59% of patients with SSTIs (Moran et al., 2006). Such findings have significant implications for ED physicians and nurse practitioners regarding the evaluation and management of patients presenting with SSTIs in EDs.
SKIN AND SOFT TISSUE INFECTIONS
Skin and soft tissue infections have a wide range of presentations including cellulitis, impetigo, boils, folliculitis, carbuncles, furuncles, and abscesses. The large majority of these presentations are a result of S. aureus. The terminologies utilized to define SSTIs are provided in Table 1 (Mosby's Medical, Nursing & Allied Health Dictionary, 1998).
The infection is characterized by the formation of purulent material due to the localized accumulation of polymorphonuclear leukocytes, with tissue necrosis involving the dermis and subcutaneous tissue (Stevens et al. 2005). Abscesses are often found in the soft tissue under the skin such as the armpit, groin, axillae, buttocks, and extremities but they may develop in any organ, such as deep organs (lungs, liver, or brain), which will require more specific treatment (Paydar, Hansen, Charlebois, Harris, and Young, 2006; Stevens et al., 2005). Skin and soft tissue abscesses occur when bacteria get into tissue below the outer layer of skin. The most common presentations with SSTIs are local pain, swelling, erythema, and local adenopathy. Spontaneous drainage of purulent material has been noted in patients with SSTIs. Fever, chills, and systemic toxicity are unusual in the absence of associated cellulitis.
Staphylococcus aureus, a relatively virulent bacterium, is the most common cause of SSTIs (Gorwitz, 2008; Hersh et al., 2008; Pallin et al., 2008; Stevens et al., 2005; Miller et al., 2007). While MRSA emerged in hospitals in the 1960s, it did not appear in the community until the 1990s. Community-acquired MRSA differs from health-associated MRSA in terms of the organism and onset of the infections. Community-acquired MRSA is defined as an MRSA infection with an onset in the community (Fridkin et al., 2005). Health-associated MRSA is defined as an MRSA infection that occurs within 48 hr or more of hospitalization (Fridkin et al., 2005; Naimi et al., 2003).
Traditionally, SSTIs in ambulatory settings were managed without routinely obtaining cultures to determine antimicrobial susceptibility; but the emergence of CA-MRSA in the community has beckoned for a clinical practice change (Gorwitz, 2008). The increase in SSTI has caused the Infectious Diseases Society of America (in press, projected publication Fall 2010) to develop a guideline for the management of SSTIs. Research studies indicate that there are wide variations on how clinicians manage patients (Stevens et al., 2005). According to the CDC (2007) guidelines for SSTIs, the first line of treatment should be incision and drainage (I&D), a culture and sensitivity, wound care and follow-up care without prescribing antimicrobials. However, cellulitis and/or treatment failure should be managed with antimicrobials (CDC, 2007). It should be noted that follow-up wound care within 48 hr is recommended to ensure proper healing of the infected site (Popvich & Hota, 2008).
Incision and drainage is the primary therapy for SSTIs management, as antibiotic treatment alone is inadequate for treating SSTIs. Most localized skin abscesses without associated cellulitis can be managed with simple I&D and do not require antibiotic treatment. However, wound culture and sensitivity should be conducted on all SSTIs as well as antibiotic treatment for patients with a comorbidity status (Stevens et al., 2005; Cenizal, et al., 2007; Rajendran et al., 2007; Romano, Lu, & Holton, 2006; Ruhe, Smith, Bradsher, & Menon, 2007). This outpatient procedure can be appropriately performed in many settings such as medical offices, as well as urgent care and ED environments.
SIGNIFICANCE OF PROBLEM
Emergency departments across the country have witnessed an increase in SSTIs with CA-MRSA noted as the most common pathogen (Gordon & Lowy, 2005; Stevens et al., 2005; Hasty et al., 2007; Jacobus, Lindsell, Leach, Fermann, Kressel, Rue, 2007). SSTIs have grown exponentially over the past decade from 1997–2005, National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey indicated that visits for SSTIs increased from 8.6–14.2 million (65% increase in frequency), and more than 95% of the aforementioned visits were consequential to abscesses and cellulitis (Hersh et al., 2008). Furthermore, annual visits for abscesses and cellulitis were documented at 4.6 million in 1997 and 9.6 million in 2005 (Hersh et al.).
Community-acquired methicillin-resistant Staphylococcus aureus currently accounts for the majority of SSTIs in both adults and children, regardless of health status (CDC, 2003a, 2003b; Gordon & Lowy, 2005; Moran et al., 2006; Sattler, Mason, & Kaplan, 2002; Davis et al., 2007; Lee et al., 2004; Moran, Amii, Abrahamian, & Talan, 2005). SSTIs can develop in patients of all age groups, most of whom have no demonstrable predisposing conditions other than nasal or skin carriers of S. aureus. According to the CDC (2005), approximately 25%–30% of the population is colonized with S. aureus in the nose. In terms of risk factors, the primary vehicle of transmission of CA-MRSA is via hands, which may become contaminated by contact with colonized or infected individuals, or devices, items, or environmental surfaces contaminated with body fluids containing CA-MRSA and poor hygiene (Gordon & Lowy, 2005). As a result of the emergence of SSTIs associated with CA-MRSA, the CDC issued clinical management guidelines to provide clinicians with a framework to utilize for the management of SSTIs (Gorwitz, Jernigan, Powers, Jernigan, & Participants in the Centers of Disease Control and Prevention-Convened Experts Meeting on Management of MRSA in the Community, 2006; Archibald, Shapiro, Pass, Rand, & Southwick, 2008; Begier et al., 2004; Bucko, Hunt, Kidd, & Hom, 2002; Davis et al., 2007; Iyer & Jones, 2004).
The CDC colleagues, led by Dr. Gorwitz, published Strategies for Clinical Management of MRSA in the Community (2006), consequential to the recognized increase in SSTIs associated with CA-MRSA in communities. The CDC (2007) also issued a treatment algorithm for the management of SSTIs in outpatients and has recommended that clinicians include MRSA in the differential diagnosis of SSTIs. Gorwitz et al. (2006) and the CDC (2007) recommended managing SSTIs with I&D of fluctuance lesions, wound cultures, patient education regarding wound care and good hygiene, and follow-up patient care within 48 hr. The CDC guidelines (CDC, 2007; Gorwitz et al., 2006) for strategically managing SSTIs in outpatients recommend antimicrobials for patients who present with cellulitis without an abscess. In terms of patients with systemic symptoms, severe local systems, immunosuppression, or failure to respond to I&D clinicians should consider antimicrobial therapy in addition to I&D (CDC, 2007; Gorwitz et al., 2006). It should be noted that the aforementioned guidelines were developed on the basis of the published literature.
The evidence is compelling that there has been an increase in SSTIs related to CA-MRSA and that CA-MRSA is the most common isolate associated with SSTIs. The prevalence and incidence of SSTIs caused by CA-MRSA has impacted all age groups, socioeconomic backgrounds, and health conditions. Furthermore, the literature reviewed indicated that there are variations among clinicians with regard to SSTIs management.
PURPOSE OF THE STUDY
The purpose of this study was to determine the prevalence and characteristics of SSTIs in the ED of a suburban hospital along with ED clinician adherence to the CDC (CDC, 2007; Gorwitz et al., 2006) Guidelines for the management and diagnosis of SSTIs. The Hospital's Institutional Review Board approved the study on December 16, 2008.
1. What was the prevalence and characteristics of SSTIs in the ED of a suburban hospital between January 1, 2008, and December 31, 2008?
2. Do ED clinicians adhere to the CDC (CDC, 2007; Gorwitz et al., 2006) Guidelines for SSTI diagnosis and management?
STUDY DESIGN AND METHODOLOGY
Context. SSTIs among patients presenting to the ED within a suburban hospital were investigated.
Objectives. The study objectives were to determine (1) the prevalence and characteristics of SSTIs and (2) adherence to CDC guidelines regarding SSTI diagnosis within a suburban hospital's ED, based on a 12-month retrospective chart review.
Design. A descriptive design was utilized for this retrospective chart review.
Data collection. Data were collected over a 12-month period (January 1, 2008–December 31, 2008) utilizing a chart review survey to electronically extract information from Wellsoft (electronic medical record system) about patients diagnosed with SSTIs. The following ICD-9-CM codes were utilized for the Wellsoft query: 680.9 (boil), 680.x (carbuncle/furuncle), 681.x (cellulitis), 682.x (abscess), 684 (impetigo), 686.x (skin/subcutaneous), and 704.8 (folliculitis). These ICD-9-CM codes were selected because they are universally utilized for coding SSTIs. Data were secured regarding each patient's age, gender, race, lesion site, wound culture results, and treatment (I&D and pharmacological therapy) from the hospital's medical record system (Wellsoft). The data extracted from Wellsoft were downloaded into Microsoft Excel and then imported into SPSS (Version 15) for analysis.
Data analysis. Data were imported into SPSS and analyzed for descriptive statistics including frequency distribution, central tendency (mean, median, and mode), and dispersion (range and standard deviation).
Setting. An ED of a suburban Philadelphia hospital. The 19-bed ED operated 7 days a week, 24 hr a day. A total of 23,478 ED patient visits were recorded for the 2008 calendar year. SSTI patients are clinically managed on the basis of collaboration between the ED clinicians (physicians and nurse practitioners or physician assistants) in lieu of a clinical practice guideline.
Study population. The study population included all patients presenting to the ED between January 1, 2008, and December 31, 2008, and assigned the ICD-9-CM codes listed in the “Data collection” section.
Primary outcome measures. The prevalence of SSTIs was calculated. A description of the patients and treatment characteristics associated with SSTIs were illustrated. A profile of the characteristics and treatment modalities of the patients was created and compared with the current CDC guidelines.
RESULTS OBJECTIVE 1
Determine the prevalence and characteristics of SSTIs in the ED.
During the 2008 calendar year, 800 patients presented to the ED with a chief complaint of a boil or abscess. The total number of ED visits for the 2008 calendar year was 23,478. Eight hundred patients received a SSTI diagnosis, which yielded a 3.41% SSTI rate. Patients with cellulitis and abscesses (ICD-9-CM 681.0, 681.1, 682.0–682.9) represented 88% (n = 705) of the 800 cases. The descriptions and frequency data for the 27 ICD-9-CM codes are presented in Table 2.
Of the 800 patients, 434 (54.3%) were men and 366 (45.83%) were women. The average age of patients in this study was 40.95 years with a median of 38 years, a mode of 26 years, and a standard deviation of 20.57 years. The age range of the study patients was from 6 months–97 years. In terms of race, Whites represented the majority of the study population at 85% (n = 680). Blacks and Hispanics represented 11% (n = 88) and 2.4% (n = 19), respectively. Seven hundred seventy-three (96.6%) of the 800 patients were Pennsylvanian residents, 11 (1.4%) were New Jersey residents, and 16 (2%) were from other states.
Emergency department visits for patients with SSTIs ranged from 37–93 visits per month during the investigation period. Patient visits to the ED for SSTIs were more frequent during the summer months, with 93 visits each in August and September followed by 82 visits in July and 80 in June. Figure 1 depicts the frequency of ED visits by month.
Assess clinician adherence to the CDC guidelines regarding SSTIs diagnosis and management.
Culture and Antimicrobial Susceptibility
Only 64 (8%) samples were collected from patients and sent to the laboratory for culture and antimicrobial susceptibility. Of the patients (n = 64, 8%) cultured, 20% (n = 13) were negative and 80% (n = 51) were positive. Of the 51 (80%) positive cultures, CA-MRSA was isolated from 40 (78%), streptococcus species from 5 (10%), and the remaining 6 cultures encompassed a variety of gram negative and positive organisms (see Figure 2). The hospital's laboratory results were reviewed. The laboratory results for the aforementioned specimens indicated sensitivity to the antimicrobials prescribed by the ED clinicians. Although cephalosporins are no longer recommended by the CDC guideline (2007), the hospital laboratory's sensitivity results indicated that cephalosporins remain effective in the population studied. It should be noted that the CDC guideline (Gorwtiz & CDC, 2006) also states that antimicrobial therapy should be guided by local susceptibility data (Figure 3).
The 51 samples collected were representative of 51 individual patients. It is difficult to determine how the study results compare with those in the literature because only 8% of the patients in the study had specimens taken. Stryjewski and Chambers (2008) noted that it is important to obtain specimens and secure susceptibility testing to document the presence of MRSA as well as guide antimicrobial therapy. It should be noted that the CDC guidelines (CDC, 2007; Gorwitz et al., 2006) recommend collecting specimens for culture and antimicrobial susceptibility testing from all patients with abscesses or purulent skin lesions.
Three hundred seventy-six of the 800 patients (47%) received at least one antibiotic. A total of 544 prescriptions were written, indicating that some patients received multiple antimicrobials. When antimicrobials were used, cephalosporins (n = 228, 41.92%) and sulfonamides (n = 223, 40.99%) were prescribed most frequently, followed by clindamycin (n = 31, 5.70%). According to the CDC guidelines (2007), antimicrobials are recommended for cellulitis, cellulitis without abscess, I&D treatment failure, systemic symptoms, severe local symptoms, or immunosuppression. Furthermore, β-lactam agents (antistaphylococcal penicillin or cephalosporin) are no longer considered first line treatment for MRSA (CDC, 2007). Consequently, clindamycin, tetracyclines (doxycycline and minocycline), trimethoprim-sulfamethoxazole, rifampin (only in combination with other agents), and linezolid are now considered the appropriate empiric outpatient antimicrobial treatment for SSTIs associated with MRSA. Therefore, the prescribing of cephalosporins to 228 patients (41.92%) was not aligned with the CDC guideline (2007). A list of the antimicrobials prescribed to the 376 patients is provided in Table 3. The diagnoses of the 376 patients receiving antimicrobials represented 23 of the 27 ICD-9-CM codes. According to the CDC guidelines for managing SSTIs in the community (2007), antimicrobials are only indicated for cellulitis represented by 12 of the ICD-9-CM codes (681, 681.1, 682.0–682.9) noted in Tables 2 and 4.
Antimicrobials were inappropriately prescribed for 11 of the 27 the ICD-9-CM codes (680.0, 680.2, 680.3, 681.02, 681.11, 683, 684, 685.0, 685.1, 686.8, and 686.9) presented in Table 4. However, according to the ICD-9-CM codes presented in Table 2, 705 patients had diagnoses that should have been treated with antimicrobials to comply with the CDC guideline (2007). However, only 544 antimicrobials were prescribed to 376 patients. According to the CDC guideline (2007), an additional 329 study patients were eligible for antimicrobial therapy but they were not prescribed antibiotics. Therefore, antimicrobials were underprescribed for the study population. Furthermore, when comparing the data in Table 4, it was indicated that 488 (89.70%) of the antimicrobials prescribed were appropriate therapy for the diagnoses. However, 56 (10.29%) antimicrobials were inappropriately prescribed (Table 4).
Incision and Drainage
Of the 800 patients, 176 (22%) were treated with I&D. Fifteen of the 27 ICD-9-CM codes were utilized for the 176 I&D, puncture drainage, or debridement patients. In terms of antimicrobial treatment, 108 (61%) of the 176 I&D patients were prescribed antibiotics. Trimethoprim and sulfamethoxazole tablets (71) and cephalexin capsules (64) were the most frequently prescribed antibiotics. Of the 108 I&D patients receiving antibiotics, 53 (61%) patients received multiple antibiotics.
Outpatient Treatment Failure
Of the 23 patients admitted for outpatient treatment failure, 30 antibiotics were prescribed to these patients. Seven patients received multiple antibiotics. The most frequently prescribed intravenous antibiotics were vancomycin, piperacillin (Zosyn), and clindamycin.
Methicillin-resistant Staphylococcus aureus has emerged as a cause of SSTIs among healthy adults and children in the community. The ED clinicians in this study encountered numerous patients with SSTIs related to CA-MRSA. The outcome of the study indicates that the SSTI rate of 3.41% was higher than other EDs across the country. Furthermore, the results from this study imply that ED clinicians practice outside of the scope of the CDC guidelines, as noted by the lack of I&D procedures, culture, and antimicrobial therapy. The study ED clinicians management of SSTI patients was congruent with the literature reviewed which indicated there was a variation in how ED clinicians treat SSTI patients. Consequently, ED clinician adherence to CDC guidelines is imperative due to the inability to follow-up with patients. Therefore, ED clinicians must understand and practice within the scope of the CDC guidelines (CDC, 2007; Gorwitz et al., 2006).
Implementation of the CDC guidelines will provide ED clinicians with an appropriate treatment protocol for managing SSTIs related to community-acquired S. aureus (CA-MRSA). Therefore, educational programs for the ED clinical staff and quarterly chart audits are indicated. Consequently, adherence to the CDC guidelines has the potential to improve patient outcomes.
Study design is a limitation of this research project. The retrospective medical chart review was another limitation because it was conducted through an electronic query. Consequently, each patient's electronic record was not reviewed because it was out of scope of this project. Therefore, individual clinical presentation data such as fluctuance, odor, and color were not obtained. Additional limitations included a single ED utilization and the inability to follow up with patients. Only 8% of the study population was cultured; therefore, this data cannot be used to extrapolate generalities or predictions about the population. Finally, the ICD-9-CM codes are a limitation because they combine cellulitis and abscess into several codes, such as 681, 681.1, and 682.0–682.9. Therefore, it was not possible to determine if a patient had cellulitis and/or an abscess.
In 1993 and 2005, Pallin et al. (2008) noted a 1.35% and 2.98% prevalence of SSTIs in U.S. EDs. Thus, the prevalence rate of 3.41% for the study population was higher than rates noted by Pallin et al. (2008). In the current study, 705 patients were diagnosed with cellulitis (Table 2), justifying clinical management with antimicrobials. However, 47% of the 800 patients received at least one antibiotic. The study data indicated that only 376 patients received antimicrobials, totaling 544 prescriptions (Table 3). It appears that some patients were prescribed antimicrobials without regard to the CDC guidelines (2006, 2007). Cephalosporins (n = 228, 41.92%), sulfonamides (n = 223, 40.99%) and clindamycin (n = 31, 5.70%) were the most frequently prescribed antimicrobials. Furthermore, 89.70% (n = 488) of the antimicrobials prescribed to the 376 patients were appropriate treatment for the diagnoses. However, 10.29% (n = 56) of the antimicrobials were prescribed inappropriately. According to the CDC guidelines (2007), antimicrobials are recommended for cellulitis, cellulitis without abscess, I&D treatment failure, systemic symptoms, severe local symptoms, or immunosuppression.
The I&D rate for the study was 22% (n = 176). Only 8% (n = 64) of the patients had specimens taken for culture and sensitivity. Seven hundred and five patients (88%) were diagnosed with ICD-9-CM codes 681, 681.1, and 682–682.9 indicating cellulitis and abscess, but only 64 specimens were taken. As indicated above, 705 patients were diagnosed with cellulitis and abscess; however, specimens were not taken from 503 patients. It should be noted that the ICD-9-CM codes do not distinguish between cellulitis and abscess. Therefore, the ICD-9-CM codes and the data collected could not support the determination of site characteristics such as fluctuance, odor, or color. In accordance with CDC guidelines, specimens should be taken for culture and sensitivity for all incisional and drainage procedures, as well as purulent lesions (CDC, 2007; Gorwitz et al., 2006).
The results from this study are similar to the reviewed literature in terms of patient presentation and clinical management. The study data indicated that SSTIs associated with CA-MRSA can afflict persons of all genders, age groups, and races. Furthermore, the study data demonstrated that there are variations in how ED clinicians manage SSTI patients with regard to wound cultures and medications, which is congruent with the findings of Stevens et al. (2005). Stevens et al. recommended clinical management of SSTIs with I&D, and a wound culture but without antimicrobial therapy unless compelling conditions exist, such as multiple lesions, gangrene, impaired host defenses, extensive cellulitis, or severe systemic symptoms of infection (i.e., high fever). Consequently, Stevens et al. concluded that high risk patients with SSTIs should be treated with I&D, wound cultures and antibiotic therapy which are congruent with CDC guidelines.
As noted by CDC guidelines (2007) for SSTIs, the first line of treatment should be I&D, a culture and sensitivity, wound care and follow-up care without prescribing antimicrobials. However, cellulitis and/or treatment failure should be managed with antimicrobials (CDC, 2007). Similar to other published studies, the results of this study suggest the underuse of obtaining specimens for culture and sensitivity testing as well as inappropriate use of antimicrobials when managing SSTI patients in a community ED. The CDC guidelines (2007) recommend antibiotic therapy for patients diagnosed with cellulitis, cellulitis without abscess, I&D treatment failure, systemic symptoms, severe local symptoms, or immunosuppression (CDC, 2007; Gorwitz et al., 2006).
In conclusion, it is recommended that ED clinicians practice within the scope of the CDC guidelines with respect to the management of SSTIs. Furthermore, ED clinicians are obligated to stay current about the clinical management of common and emerging organisms in their patient populations.
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Sattler, C. A., Mason, E. O., Jr., & Kaplan, S. L. (2002). Prospective comparison of risk factors and demographic and clinical characteristics of community-acquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children. Pediatric Infectious Diseases Journal, 21
Stevens, D. L., Bisno, A. L., Chambers, H. F., Everett, E. D., Dellinger, P., Goldstein, E. J., ...; Wade, J. C. (2005). Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 41
Stryjewski, M. E., & Chambers, H. F. (2008). Skin and soft tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Clinical Infectious Diseases, 46
community-acquired methicillin-resistant Staphylococcus aureus; community-associated methicillin-resistant Staphylococcus aureus; emergency department; skin and soft tissue infections
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