MRSA Infections of the Skin

Author: Dr Bryan Cho University of California SF 2008-07-28

Methicillin Resistant Staphylococcus Aureus (MRSA) Infections of the Skin
NTRODUCTION

Bacteria are microorganisms that are found almost everywhere. Most bacteria are harmless but some can cause infection. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that has emerged as a major cause of skin infections among otherwise healthy adults and children in the community. This bacterium is dangerous because it causes infections that cannot be treated with commonly used antibiotics that in the past would destroy the bacteria and cure the infection. Moreover, left untreated these infections can have serious complications. This article will discuss the risk factors for MRSA infections, what MRSA skin infections look like, and how they can be treated and avoided.

                                                                                   

HEALTHCARE ASSOCIATED-MRSA

MRSA was first diagnosed in 1961 as bacteria associated with serious infections that occurred in hospitalized patients or patients in healthcare facilities such as nursing homes or dialysis centers. MRSA infections that occurred in healthcare facilities were termed healthcare associated-MRSA (HA-MRSA). These infections were often serious and potentially life-threatening and included bloodstream infections, surgical site infections or pneumonia. Since being discovered, the number of MRSA infections has increased dramatically. In 1974, MRSA infections accounted for 2% of the total number of Staphylococcus infections; in 1995 it was 22%; in 2004 it was 63%[1]

 

HA-MRSA risk factors include:[2]^,[3]

1. Weakened immune system and severe illness
2. Previous exposure to antimicrobial agents
3. Surgery or open wounds
4. Residence in a long term healthcare facility (nursing home, skilled nursing facility)
5. Underlying disease or conditions, particularly:
1. Chronic renal disease
2. Insulin-dependent diabetes mellitus
3. Peripheral vascular disease
4. Dermatitis or skin lesions
6. Invasive devices (Urinary catheterization, intravenous lines (IV), Dialysis, tracheotomies, G tubes)
7. Patients in the intensive care unit (ICU)
8. Male, age older than 65
9. Repeated contact with the healthcare system
10. Previous colonization by a multidrug-resistant organism

 

COMMUNITY ACQUIRED-MRSA

In the past few years, a separate strain of MRSA bacteria has developed that affects healthy members of the community. This community acquired MRSA (CA-MRSA) has caused outbreaks of disease among professional athletes, high school athletic teams, and in day care settings. Developing a CA-MRSA infection does not imply any impairment in immune system function. The average age of patients with CA-MRSA infections is age 23 compared to age 68 for HA-MRSA.[4]  Unlike HA-MRSA, CA-MRSA rarely causes life threatening infections. CA-MRSA most commonly causes skin infections such as boils or pimples. Because these infections can occur abruptly on otherwise normal skin, CA-MRSA infections are frequently mistaken for spider bites.

 

CA-MRSA may occur in the following populations:

1. The young and healthy, especially those who live in crowded conditions or have close physical contacts with others, including:
1. Athletes
2. Prisoners
3. Soldiers
2. Selected ethnic populations
3. IV drug users

   

	CA-MRSA	HA-MRSA
At-risk groups or condition	Children, athletes, prisoners, soldiers, selected ethnic populations, IV drug use	Long term care facility residents, diabetics, dialysis patients, prolong hospitalization, ICU patients, I.V. lines, indwelling catheters, open wounds
Antimicrobial resistance	Resistance to the Betas lactam class of antibiotics (Methicillin, penicillin, cephalosporin)	Resistance to multiple antibiotics is common
Type of disease caused	Skin infections	Blood stream infections, skin infections, pneumonia, urinary tract infections
Additional Information	http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html	http://www.cdc.gov/ncidod/dhqp/ar_mrsa.html

 

Table 1. CA-MRSA versus HA-MRSA.

   

SKIN INFECTIONS CAUSED BY MRSA:

Roughly 85% of CA-MRSA infections develop in the skin.[5] Each year there are an estimated 12 million outpatient (e.g., physician offices, emergency and outpatient departments) healthcare visits for skin and soft tissue infections in the United States[6].  In one study, three out of four patients seen in the emergency room for skin infections had Staphylococcal aureus infections and over 50% had MRSA infections.[7]

 

Most MRSA skin infections look like (Described below.):

 

o       Impetigo

o       Many small pimple-like bumps (folliculitis)

o       Large painful boils (furuncle or carbuncle)

o       Spider or insect bites

 

Less common and more serious skin and soft tissue infection caused by MRSA include:

 

o       Cellulitis

o       Infected wounds

 

Impetigo is a superficial skin infection that occurs on open, exposed areas of skin. This infection occurs most commonly in children but usually does not cause serious illness. The infection starts at sites of minor skin trauma such as insect bites or abrasions. The affected skin may develop small (less than 5mm) fluid filled bumps that develop golden honey-crusting when bumps burst. Usually, multiple skin lesions are present. Impetigo is easily spread within families and close contacts.  Other risk factors for infection include warm, humid conditions and poor hygiene. Impetigo is most commonly caused by a bacterium called Streptococcus, but more and more frequently, impetigo is caused by MRSA; CA-MRSA now accounts for 7-20% of impetigo infections.[8]  Impetigo caused by Streptococcus and CA-MRSA look identical.

   

Figure 1: Impetigo

 

Folliculitis is a superficial infection of the hair follicle. Folliculitis typically starts when hair follicles are damaged by trauma from scratching or shaving, from friction due to tight fitting clothing, or due to blockage. As a result, damaged follicles become infected with bacteria that cause red bumps or pimples centered on hair follicles. Buttocks, thighs, back and upper arms are commonly affected sites. The lesions of folliculitis are often clustered in groups and itch is the most common symptom. Folliculitis does not cause systemic symptoms such as fever or chills. About 3-25% of cases of folliculitis are due to CA-MRSA[9] other cases of folliculitis may be caused by non-MRSA strains of S. aureus, Pseudomonas aeruginosa, or fungi such as Candida or Pityrosporum

Figure 2: Folliculitis

Boils (Furuncle/Carbuncle):

Boils are caused by an infection, usually by Staph aureus that occurs deep within the hair follicle. These infections start as red, tender areas of skin that form large circular tender bumps filled with pus. A soft, white/yellow area will often form at the center of the boil where the pus may drain. Boils are typically larger than five millimeters. A single boil is called a furuncle; a network of interconnected boils is called a carbuncle. Boils can frequently be confused with spider or insect bites because they occur abruptly on skin without previous trauma. Symptoms like fevers and chills rarely occur and if present may be suggestive of a more serious infection. A 2004 study found that approximately 76% of purulent (pus containing) skin and soft tissue infection in adults seen in emergency rooms were caused by Staph aureus. Of these infections, 78% were cause by MRSA[10].

 

Figure 3: Boil  

Cellulitis:

Cellulitis is a rapidly spreading infection of the deep fat and connective tissue under the skin. Bacteria usually enter through breaks in the skin caused by trauma (cuts, scrapes, blisters, burns, surgery or insect/animal bites), infection (athlete’s foot, boils) or external medical devices (catheter).  Characteristic findings associated with cellulitis include:

1.      Swelling

2.      Bright red skin, pain (erythyma)

3.      Local warmth of the infected skin.

4.      Pain

Cellulitis can also cause fever, chills, red streaks along draining lymph vessels (lymphangitis), and enlarged lymph nodes. Skin on the lower legs is most commonly affected by this infection, though cellulitis can occur on any part of the body.  Alcoholism, immunosuppression, diabetes mellitus, malignancy, intravenous drug abuse, and peripheral vascular disease are all risk factors for cellulitis. Cellulitis is rarely due to bacteria arriving from a distant source via the bloodstream (bacteremia).

 

Figure 4a: Cellulitis

Figure 4b: Lymphangitis  

SERIOUS COMPLICATIONS

When MRSA infections are neglected or insufficiently treated, they may develop into serious infections that affect deeper underlying tissue (myositis, osteomyelitis), spread to the bloodstream (bacteremia, sepsis), or involve internal organs (pneumonia, endocarditis).  Clinical presentations associated with invasive CA-MRSA include bacteremia (65.1%), pneumonia (14.0%), cellulitis (22.7%), osteomyelitis (8.1%), endocarditis (12.6%) and septic shock (3.8%).[11]

 

Patients with severe CA-MRSA infections requiring hospitalization and treatment include those who have fever, large abscesses, low blood pressure, blackened tissue (necrosis), severe bleeding and gas within infected tissue. In addition, other certain patient populations such as the immunocompromised, diabetic and infants younger than 6 months may require hospitalization. When serious systemic symptoms like fevers, chills or low blood pressure develop, you should be evaluated immediately by your physician.

   

TREATMENT

The treatment for MRSA skin infection depends on severity of the infection, the type of skin infection, and the patient’s risk factors for MRSA.

 

Impetigo:

For patients with a limited numbers of skin lesions, impetigo can be treated with the topical antibiotic mupirocin. When the disease is more severe, oral antibiotics should be used. The choice of antibiotic will depend on the resistance pattern of the infecting bacterium. For those cases of impetigo caused by CA-MRSA, sulfa drugs, tetracyclines, and clindamycin are usually effective. Once treatment is initiated, most cases of impetigo will resolve in 10-14days. Gentle washing of the affected skin to remove debris and crust is generally recommended. The American Academy of Pediatrics recommends that children with impetigo be with withheld from child care settings for the first 24-hours of antibiotic treatment. Precautionary measures that limit the spread of impetigo include hand washing, keeping the infected skin covered, and avoiding sharing common items (towels, clothing).

 

Folliculitis:

Treatment of CA-MRSA folliculitis varies but includes topical antibiotics, oral antibiotics and prophylactic use of antibacterial detergents.  Many physicians start with topical antibiotics but may use oral antibiotics if topical antibiotics are ineffective, or the folliculitis is widespread. Most cases of folliculitis will respond to treatment and resolve in 10-14 days, however, a portion of patients may develop recurrent episodes.  Recurrent folliculitis may suggest possible bacterial colonization (see below) and require decolonization treatment. Folliculitis can also evolve into deeper, larger lesions called furuncles (see below).

 

Boils (Furuncle/Carbuncle):

The most common presentation of CA-MRSA is as a boil, which is typically treated with incision and drainage. This treatment removes the source of infection and will cure most healthy people with no systemic signs of infection (e.g., fever, chills, elevated white blood cell count) when boils are less than five centimeters in diameter. In a recent randomized, placebo controlled trial in adult patients with deep skin abscesses, the majority of which were caused by MRSA, treatment success rates were over 90% for patients treated with incision and drainage alone.[12] Most recent Centers for Disease Control and Prevention (CDC) guidelines suggest that physicians should collect specimens for culture and antimicrobial susceptibility testing from all patients with abscesses or pus-containing skin lesions, particularly those with severe local infections, systemic signs of infection, or history suggesting connection to a cluster or outbreak of infections among epidemiologically linked individuals.

 

To perform an I&D, the skin is numbed with local anesthetic. A small incision is made on the skin overlying the boil and the pus is drained. Some abscesses have pockets of pus that must be broken up to release all of the pus. Packing material, such as gauze or gauze tape, may be placed in the drained abscess to keep the skin from closing and allow the wound to drain as it heals from the inside out. For patients with suspected MRSA, a sample of drained pus or of infected tissue will be sent for culture and susceptibility testing. If an I&D is not performed, your physician may remove fluid within a boil using a needle (aspiration) and send the fluid for culture. A culture can help confirm a case of suspected MRSA and guide the selection of an antibiotic when appropriate. In cases where a course of antibiotics was prescribed before culture results are available, the culture and sensitivity results help confirm or guide selection of the correct antibiotic.

  

Patients with treated with I&D on an outpatient basis should contact their physician if they develop fevers/chills, worsening local symptoms or if their symptoms do not improve within 48 hours.

 

For some patients, an I&D may be the primary mode of therapy however, other patients may be treated with both an I&D and oral antibiotics.  Factors which may influence a clinician to supplement I&D with antibiotics include:

• Severity and rapidity of progression of the skin infection or the presence of associated cellulitis
• An infected site more than five centimeters in diameter associated with failure of incision and drainage without effective antimicrobial therapy
• Signs and symptoms of systemic illness (fever, chills, elevated white blood cell count)
• Associated co-morbidities or immunosuppression (diabetes mellitus, neoplastic disease, HIV infection, transplantation, obesity, poor tissue oxygenation, nicotine use, poor nutritional status)
• Extremes of patient ages (very young or elderly)
• Location of abscess in area that may be difficult to drain completely
• Association with septic phlebitis or major vessels (central face)
• Lack of response to initial treatment with I&D alone

 

The choice of antibiotic therapy in treatment of CA-MRSA infections depends on the severity of the infection and the frequency of MRSA infections in the community. Local susceptibility data is often used to guide treatment.

 

Cellulitis:

Treatment of cellulitis consists of oral antibiotics and resting the affected limb or area. In severe cases, patients may require admission to a hospital for intravenous antibiotics and debridement of dead or infected tissue. Wounds or broken skin should be cleansed and bandaged. Wound dressings should be changed daily or when they become saturated or dirty.

With proper treatment most cases of cellulitis resolve in one to two weeks although more severe cases may take months to resolve. If untreated, cellulitis can result in severe debilitation or even death.

   

ANTIBIOTICS:

Both CA-MRSA and HA-MRSA are resistant to traditional anti-staphylococcal beta-lactam antibiotics, such as cephalexin. Sulfa drugs, tetracyclines, and clindamycin are usually effective at treating CA-MRSA; HA-MRSA is resistant even to these antibiotics. To treat HA-MRSA an intravenous administered antibiotic such as vancomycin or other newer oral medication such as linezolid are often required.  A brief description of antibiotics that may be used to treat CA-MRSA or HA-MRSA is provided below.

Cephalosporins

Initial empiric antibiotic of choice in an uncomplicated skin infection in a community with higher rates of Methicillin sensitive Staph aureus than MRSA

 

Sulfa

Trimethoprim-sulfamethoxazole (Septra) remains the drug of choice for confirmed uncomplicated CA-MRSA especially when the rate of inducible clindamycin resistance is high. However, this class of medications does not provide coverage for beta-hemolytic streptococci which may also be the cause for erysipelas or cellulitis-like infections

These antibiotics are not recommended for women in third trimester of pregnancy or in infants less than two months of age.

 

Tetracyclines

Tetracyclines are effective on many strains of CA-MRSA. A small case series has demonstrated that doxycycline and minocycline were adequate for the treatment of MRSA soft tissue skin infections. This class of antibiotics is a good alternative treatment for confirmed CA-MRSA in cases where sulfa drugs are not tolerated or contraindicated.

However, they do not have activity against beta-hemolytic streptococcus and are contraindicated in children younger than age eight and during pregnancy

 

Clindamycin

Traditionally used for empiric therapy for uncomplicated skin infection alone or in combination with rifampin. A major advantage over trimethoprim-sulfamethoxazole (sulfa) is that when used empirically, clindamycin has better coverage for beta-hemolytic streptococci, another common cause of skin infections. Some strains of MRSA have developed inducible resistance to this class of antibiotics, therefore clindamycin not recommended in areas where inducible clindamycin resistant MRSA is present in greater than 10-15% of the local isolates. If clindamycin therapy is being considered, sensitivity testing for inducible clindamycin resistance should be performed using the D-zone disk-diffusion testing.

 

Rifampin

Because rifampin achieves high concentrations in mucosal surfaces, this antibiotic may promote eradication of MRSA colonization. However, because resistant strains of S. aureus develop rapidly when used as a single agent, rifampin should be used simultaneously with other antibiotics that target MRSA. Drug-drug interactions are common with rifampin and should be minimized prior to use. Women on contraception are recommended to use a second form of contraception as rifampin can decrease the effectiveness of oral contraceptives

 

Fluoroquinolones

Fluoroquinolones such as ciprofloxacin or levofloxacin are common first-line treatments for hospitalized patients with severe invasive S. aureus infection. Because of relatively high prevalence of resistance in the community and potential for rapid development of resistance, these antibiotics are not the optimal choice for the empiric treatment of CA-MRSA[13] Use of fluoroquinolones should be reserved for confirmed susceptible CA-MRSA infections when the use of other antibiotics is contraindicated. A major limitation of fluroquinolones for treatment of MRSA infections is that resistance can develop relatively quickly. Although many CA-MRSA strains remain sensitive to fluoroquinolones, resistance is emerging and overuse of these antibiotics favors the emergence of new CA-MRSA resistant strains

 

Macrolides/Azalides:

Erythromycin, clarithromycin and azithromycin are all FDA approved for the treatment o uncomplicated skin infections caused by S. aureus. Resistance to macrolides is common among CA-MRSA isolates which limits their usefulness as alternative agents for empiric treatment in areas with MRSA is high.

 

Vancomycin

Considered first line treatment for hospitalized patients with severe staphylococcal infections.

 

Linezolid

FDA approved for the treatment of complicated skin infections and hospital acquired pneumonia due to MRSA in adults. Has demonstrated superior tissue penetration in bone and muscle compared to vancomycin and has excellent penetration into skin and soft tissue. Available in a 100% bioavailable oral formulation, that can reduce hospital stays and duration of intravenous treatment. Due to the high bioavailability in oral form, linezolid can be used as an alternative treatment in patient with impaired renal function or poor venous access. This medication is expensive and has serious side effects that may include myelosuppression, peripheral and optic neuropathy and thrombocytopenia.

   

COLONIZATION

Rates of MRSA infection or recurrence are higher in people who are colonized with MRSA.

• Colonization means that the organism is present in or on the body but does not cause disease or symptoms.
• Infection means the organism is both present and causes disease.

 

The nostril and nasal passages (anterior nares) are the most common site of colonization by MRSA. Elimination of the bacteria at this site may prevent MRSA infections from recurring. However, MRSA colonization can also occur at sites other than the nose such as the throat, armpit, anus, and perineum. These sites may be important in development and transmission of the infection as well as in persistence or reappearance of colonization after use of nasal decolonization agents. Although having a MRSA infection raises the likelihood of having MRSA colonization, not all MRSA patients are colonized.[14] In a 2001-2002 US survey of non-institutionalized individuals, 0.8% of the U.S. population is colonized with MRSA.[15] Household or close contacts of MRSA colonized or infected patients are 7.5 times more likely to be colonized.[16]

 

Testing for Colonization

Testing for nasal colonization involves bacterial cultures of nasal swabs. Recent CDC guidelines suggest it is not necessary to routinely collect nasal cultures in all patients presenting with possible MRSA infection.

 

Decolonization Therapy

Decolonization is generally not recommended unless the patient has had recurrent infection; multiple infections recur within the same family or group of individuals; or if an individual is at higher risk for serious infection (e.g. diabetes, immunosuppressed). A number of different methods have been suggested with varying success. Most use a combination of oral antibiotics or an oral and topical antibiotic simultaneously. However, even the most intensive decolonization protocol results in eradication only about 66% of time. When attempting to eliminate MRSA colonization in a group, all members should receive the decolonization regimen simultaneously to decrease the risk of recolonization and to decrease the potential for emergence of resistance. Patients with indwelling lines, catheters, tracheostomies, G tubes, and other invasive devices are not good candidates for decolonization because such therapy is not likely to eradicate organisms from these surfaces.

 

Topical + Oral antibiotic

Mupirocin is the most effective among topical antibiotics for decolonization of the intranasal CA-MRSA. The antibiotic should be applied twice per day to both nostrils/nasal passages for five to10 days while on an appropriate oral antibiotic. For long term prevention, one study showed monthly use of mupirocin ointment applied intranasally twice per day for five days each month reduced nasal colonization and led to fewer cases of folliculitis or boils in 8/17 treated patients compared to 2/17 who received placebo.[17]

 

Rifampin + Other Oral Antibiotics

Rifampin is an oral antibiotic that achieves high concentrations in mucosal surfaces and is effective at reducing colonization by MRSA. However rifampin-resistant strains of MRSA develop rapidly when used as a single agent. Therefore, rifampin must be used in combination with another appropriate oral antibiotic that is active against MRSA for proper MRSA decolonization. Most courses of rifampin range from seven to 10 days with a daily dose of 600mg.

 

Rifampin should be used with caution because drug-drug interactions are common with rifampin. Women on oral contraception are recommended to use a second form of birth control because rifampin may decrease the effectiveness of oral contraceptives.

   

PREVENTION

The main mode of MRSA transmission is through direct physical contact, not through the air. Good hand cleansing is the single most important preventative measure to avoid for transmission of MRSA. Spread may also occur through contact with objects contaminated with MRSA infected skin or body fluids. Always clean hands immediately after touching infected skin or with any item that has come in direct contact with a draining wound. When washing hands, use an alcohol based hand gel or wash with an antibacterial soap for at least 15 seconds before rinsing with warm water.  MRSA may survive on inanimate objects for up to 3 days. Clean equipment and other environmental surfaces than contact bare skin contact with an over the counter detergent/disinfectant that specifies Staphylococcus aureus on the product label and is suitable for the type of surface being cleaned

   

For caregivers of MRSA infected people, general recommendations are that caregivers should wash their hands with soap and water after physical contact with the infected or colonized person and before leaving the home.

·        Towels used for drying hands after contact should be used once

·        Disposable gloves should be worn if contact with body fluids is expected and hands should be washed after removing gloves

·        Linens should be changed and washed routinely if they are soiled

·        The infected person’s environment should be cleaned routinely

 

Controlling transmission

Infected or colonized patients should be able to participate in school/work or other social activities if draining wounds are covered, bodily fluids are contained, and the patients observe good hygienic practices.

 

Other MRSA prevention tips:[18]

§         Keep draining wounds covered with clean, dry, bandages.

§         Wash hands regularly with soap and water or alcohol-based hand gel (if hands are not visibly soiled). Always clean hands immediately after touching infected skin or any item that has come in direct contact with a draining wound.

§         Maintain good general hygiene with regular bathing.

§         Do not share items that may become contaminated with wound drainage, such as towels, clothing, bedding, bar soap, razors, and athletic equipment that touches the skin.

§         Launder clothing that has come in contact with wound drainage after each use and dry thoroughly.

§         If you are not able to keep your wound covered with a clean, dry bandage at all times, do not participate in activities where you have skin to skin contact with other persons (such as athletic activities) until your wound is healed.

§         Clean equipment and other environmental surfaces with which multiple individuals have bare skin contact. Use an over the counter detergent/disinfectant that specifies Staphylococcus aureus on the product label and is suitable for the type of surface being cleaned.

 

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[1] Klevens RM, Edwards JR, Tenover FC, McDonald LC, Horan T, Gaynes R; National Nosocomial Infections Surveillance System. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus inintensive care units in US hospitals, 1992-2003. Clin Infect Dis. 2006 Feb 1;42(3):389-91.

[2] Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH,Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK,Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators.Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71.

[3] Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH,Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK,Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators.Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71.

[4] Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J,Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.JAMA. 2003 Dec 10;290(22):2976-84.

[5] Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J,Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.JAMA. 2003 Dec 10;290(22):2976-84.

[6] McCaig LF, McDonald LC, Mandal S, Jernigan DB. Staphylococcus aureus-associated skin and soft tissue infections in ambulatory care. Emerg Infect Dis. 2006 Nov;12(11):1715-23.

[7] Abrahamian FM, Moran GJ. Methicillin-resistant Staphylococcus aureus infections.N Engl J Med. 2007 Nov 15;357(20):2090;

[8] Cohen PR . Community-acquired methicillin resistant Staphylococcus aureus skin infections: a review of epidemiology, clinical fetures, management and prevention. Int. J. Dermatol. 2007 Jan;46(1):1-11

[9] Cohen PR . Community-acquired methicillin resistant Staphylococcus aureus skin infections: a review of epidemiology, clinical fetures, management and prevention. Int. J. Dermatol. 2007 Jan;46(1):1-11

[10] Abrahamian FM, Moran GJ. Methicillin-resistant Staphylococcus aureus infections.N Engl J Med. 2007 Nov 15;3(20):2090;

[11] Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH,Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK,Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators.Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71.

[12] Rajendran PM, Young D, Maurer T, Chambers H, Perdreau-Remington F, Ro P, Harris H. randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemother. 2007 Nov;51(11):4044-8

[13] Gorwitz RJ, Jernigan, DB, Powers JH, Jernigan JA and Parcipants of the Centers for Disease Control and Prevention-Convened Experts Meeting on Management of MRSA in the Community. Strategies for Clinical Management of MRSA in the Community: Summary of Experts’ Meeting Convened by the Centers of Disease Control and Prevention, March 2006

[14] Frazee BW, Lynn J, Charlebois ED, Lambert L, Lowery D, Perdreau-Remington F. High prevalence of methicillin-resistant Staphylococcus aureus in emergency department skin and soft tissue infections.Ann Emerg Med. 2005 Mar;45(3):311-20.

[15] Kuehnert MJ, Kruszon-Moran D, Hill HA, McQuillan G, McAllister SK, Fosheim G, McDougal LK, Chaitram J, Jensen B, Fridkin SK, Killgore G, Tenover FC. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001-2002. J Infect Dis. 2006 Jan 15;193(2):172-9.

[16] Calfee DP, Durbin LJ, Germanson TP, Toney DM, Smith EB, Farr BM.  Spread of methicillin-resistant Staphylococcus aureus (MRSA) among household contacts of individuals with nosocomially acquired MRSA.Infect Control Hosp Epidemiol. 2003 Jun;24(6):422-6.

[17] Raz R, Miron D, Colodner R, Staler Z, Samara Z, Keness Y. A 1-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection.Arch Intern Med. 1996 May 27;156(10):1109-12.

[18] Gorwitz RJ, Jernigan, DB, Powers JH, Jernigan JA and Parcipants of the Centers for Disease Control and Prevention-Convened Experts Meeting on Management of MRSA in the Community. Strategies for Clinical Management of MRSA in the Community: Summary of Experts’ Meeting Convened by the Centers of Disease Control and Prevention, March 2006