METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) SKIN INFECTIONS

Stephen A. Martin, MD, EdM • Paul P. Belliveau, PharmD

 BASICS

DESCRIPTION

•  Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has unique properties allowing the organism to cause skin and soft tissue infections (SSTIs) in healthy hosts:

–  CA-MRSA has a different virulence and disease pattern than hospital-acquired MRSA (HA-MRSA).

•  CA-MRSA infections impact patients who have not been recently (<1 year) hospitalized or had a medical procedure (e.g., dialysis, surgery, catheters).

•  Incidence of CA-MRSA has increased in the United States, recently plateauing between 2005 and 2010.

•  CA-MRSA typically causes mild to moderate SSTIs (abscesses, furuncles, and carbuncles):

–  Severe or invasive CA-MRSA disease is less frequent but can include:

  Necrotizing pneumonia with abscesses

  Necrotizing fasciitis

  Septic thrombophlebitis

  Sepsis

  Osteomyelitis

•  Although less frequent, HA-MRSA can still cause SSTIs in the community.

•  System(s) affected: skin, soft tissue

EPIDEMIOLOGY

•  Predominant age: all ages, generally younger

•  Predominant sex: female > male

Incidence

•  316/100,000/year (2004 to 2005)

•  46/100,000/year pediatric MRSA SSTI hospitalizations (2009)

Prevalence

•  Significantly affected by local epidemiology

•  25–30% of U.S. population are colonized with S. aureus; up to 7% are colonized with MRSA.

•  CA-MRSA isolated in ~60% of SSTIs presenting to emergency departments (range 15–74%). In 1993, 1.5 million SSTIs were seen in U.S. emergency rooms. In 2005, this had increased to 3.4 million. Hospital admissions for SSTIs increased 29% between 2000 and 2004.

•  CA-MRSA accounts for up to 75% of all community staphylococcal infections in children.

ETIOLOGY AND PATHOPHYSIOLOGY

•  First noted in 1980. Current U.S. CA-MRSA epidemic began in 1999. The US-300 clone is predominant.

•  CA-MRSA is distinguished from HA-MRSA by

–  Lack of a multidrug-resistant phenotype

–  Presence of exotoxin virulence factors

–  Type IV Staphylococcus cassette cartridge (contains the methicillin-resistance gene mecA)

RISK FACTORS

•  ~50% of patients have no obvious risk factor.

•  Use of any antibiotic in the past month

•  Presence of an abscess

•  Reported “spider bite”

•  History of MRSA infection

•  Close contact with a similar infection

•  Children, particularly in daycare centers

•  Competitive athletes

•  Incarceration

•  Hospitalization in the past 12 months

GENERAL PREVENTION

•  Colonization (particularly of the anterior nares) is a risk factor for subsequent S. aureus infection. Not certain if similar for CA-MRSA. Oropharyngeal and inguinal colonization are equally prevalent.

•  CA-MRSA may be transmitted more easily through environmental and household contact (1)[B].

•  Health care workers are a primary MRSA vector for hospitalized patients, reinforcing the need for meticulous cleaning of hands and equipment.

•  Research for a vaccine is underway.

•  CDC guidance for prevention of MRSA in athletes: http://www.cdc.gov/mrsa/community/team-hc-providers/advice-for-athletes.html

COMMONLY ASSOCIATED CONDITIONS

Many patients are otherwise healthy.

 DIAGNOSIS

HISTORY

•  Review potential risk factors.

•  “Spider bite” is commonly confused with MRSA—patients may report an unclear history of spider bite.

•  Prior MRSA skin infection

•  Risk factors alone cannot rule in or rule out a CA-MRSA infection.

PHYSICAL EXAM

•  Furuncles and/or carbuncles, sometimes with surrounding cellulitis. A nonsuppurative cellulitis is also possible, although it is a less common presentation of CA-MRSA.

•  Erythema, warmth, tenderness, swelling

•  Fluctuance

•  Folliculitis, pustular lesions

•  Appearance like an insect or spider bite

•  Tissue necrosis

DIFFERENTIAL DIAGNOSIS

SSTIs due to other organisms

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

•  Wound cultures establish definitive diagnosis. Recent guidelines recommend cultures only when a purulent lesion is accompanied by systemic signs of illness or immunocompromise (2)[B].

•  Susceptibility testing; many labs use oxacillin instead of methicillin.

•  A “D-zone disk-diffusion test” evaluates for inducible clindamycin resistance in CA-MRSA resistant to erythromycin.

•  In unclear cases, ultrasound may help identify abscesses (3,4)[A].

•  CT or MRI may show fascial plane edema in suspected necrotizing fasciitis. DO NOT DELAY surgical intervention in such cases.

Diagnostic Procedures/Other

Purulent lesions should be incised and drained (I&D); needle aspiration is not recommended (2).

 TREATMENT

•  Recent guidelines recommend antibiotics that are active against MRSA for patients with carbuncles or abscesses if patients do not respond to initial antibiotic treatment, have markedly impaired host defenses, or present with systemic inflammatory response (SIRS) and hypotension (2).

•  Routine use of agents to eliminate MRSA colonization for patients with active infection or their close contacts is not currently recommended.

•  Most CA-MRSA infections are localized SSTIs and do not require hospitalization or vancomycin.

•  Base initial empirical antibiotic coverage on local CA-MRSA prevalence and individual patient risk factors.

•  http://www.cdc.gov/mrsa/pdf/Flowchart_pstr.pdf

GENERAL MEASURES

•  Modify therapy based on culture and susceptibility.

•  Determine if household or other close contacts have SSTI or other infections and evaluate accordingly.

•  Treat underlying conditions (e.g., tinea pedis).

•  Restrict contact if wound cannot be covered.

•  Elevate affected area.

MEDICATION

ALERT

For purulent infections, consider surgical drainage, wound culture, and narrow-spectrum antimicrobials:

•  I&D may have more impact than antibiotics in mild cases for both adults and children.

•  Patients with an abscess are frequently cured by incision and drainage alone.

•  Packing does not appear to improve outcomes (3)[A].

•  Moist heat may work for small furuncles.

First Line

CA-MRSA SSTIs: 7- to 14-day course (depends on severity and clinical response):

•  Trimethoprim/sulfamethoxazole (TMP-SMX): DS (160 mg TMP and 800 mg of SMX) 1 to 2 tablet(s) PO BID daily (8 to 12 mg/kg/day of trimethoprim component in 2 divided doses for children)

•  Doxycycline or minocycline: 100 mg PO BID (children >8 years and <45 kg; 2 to 5 mg/kg/day PO in 1 to 2 divided doses, not to exceed 200 mg/day; children >8 years and >45 kg, use adult dosing), taken with a full glass of water

•  Clindamycin: 300 to 450 mg PO QID (30 to 40 mg/kg/day PO in 3 divided doses for children), taken with full glass of water. Check D-zone test in erythromycin-resistant, clindamycin-susceptible S. aureus isolates (a positive test indicates induced resistance—choose a different antibiotic).

•  CA-MRSA is resistant to β-lactams (including oral cephalosporins and antistaphylococcal penicillins) and often macrolides, azalides, and quinolones.

•  Although most CA-MRSA isolates are susceptible to rifampin, this drug should never be used as a single agent because of concerns regarding resistance. The role of combination therapy with rifampin in CA-MRSA SSTIs is not clearly defined.

•  There has been increasing resistance to clindamycin, both initial (~33%) and induced.

•  Although CA-MRSA isolates are susceptible to vancomycin, oral vancomycin cannot be used for CA-MRSA SSTIs due to limited absorption.

Second Line

Treat severe CA-MRSA SSTIs requiring hospitalization and HA-MRSA SSTIs using:

•  Vancomycin: Generally, 1 g IV q12h (30 mg/kg/day IV in 2 divided doses; in children: 40 mg/kg/day IV in 4 divided doses) vancomycin-like antibiotics that require only 1 or 2 doses may soon be more broadly available (5)[A].

•  Linezolid: 600 mg IV/PO BID uncomplicated: children <5 years of age, 30 mg/kg/day in 3 divided doses; 20 mg/kg/day IV/PO in 2 divided doses for children 5 to 11 years of age; children >11 years, use adult dosing. Complicated: birth to 11 years, 30 mg/kg/day IV/PO in 3 divided doses; older, use adult dosing

–  Linezolid seems to be more effective than vancomycin for treating people with SSTIs, but current studies have high risk of bias.

•  Clindamycin: 600 mg IV TID; in children, 10 to 13 mg/kg/dose q6–8h up to 40 mg/kg/day

•  Daptomycin: 4 mg/kg/day IV (safety/efficacy not established in patients <18 years of age) if no pulmonary involvement

•  Ceftaroline 600 mg BID IV (for adults)

Pediatric Considerations

•  Tetracyclines not recommended <8 years of age

•  TMP-SMX not recommended <2 months

Pregnancy Considerations

•  Tetracyclines are contraindicated.

•  TMP-SMX not recommended in 1st or 3rd trimester

Geriatric Considerations

A recent review notes no prospective trials in this age group and recommends use of general adult guidelines.

ISSUES FOR REFERRAL

Consider consultation with infectious disease in cases of

•  Refractory CA-MRSA infection

•  Plan to attempt decolonization

SURGERY/OTHER PROCEDURES

Progression to serious SSTIs, including necrotizing fasciitis, is possible and mandates prompt surgical evaluation.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

•  Consider admission if:

–  Systemically ill

–  Systemically well with comorbidities that may delay or complicate resolution of SSTI

–  Presence of SSTI complications (sepsis, necrotizing fasciitis) and comorbidities

–  Alternatives to inpatient admission include observation units and outpatient parenteral antimicrobial therapy (OPAT) programs in carefully selected cases.

•  Nursing: contact precautions

•  If admitted for IV therapy, assess the following before discharge:

–  Afebrile for 24 hours

–  Clinically improved

–  Able to take oral medication

–  Has adequate social support and is available for outpatient follow-up

 ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

For outpatients:

•  Return promptly with systemic symptoms, worsening local symptoms, or failure to improve within 48 hours. Consider a follow-up within 48 hours of initial visit to assess response and review culture.

PATIENT EDUCATION

•  Cover draining wounds with clean, dry bandages.

•  Clean hands regularly with soap and water or alcohol-based gel; hot soapy shower daily

•  Do not share items that may be contaminated (including razors or towels).

•  Clean clothes, towels, and bed linens.

•  National MRSA Education Initiative: www.cdc.gov/mrsa/

•  A mixture of 1/4 cup household bleach diluted in 1 gallon of water can be used to clean surfaces.

PROGNOSIS

In outpatients, improvement should occur within 48 hours.

COMPLICATIONS

•  Necrotizing pneumonia or empyema (after an influenza-like illness)

•  Necrotizing fasciitis

•  Sepsis syndrome

•  Pyomyositis and osteomyelitis

•  Purpura fulminans

•  Disseminated septic emboli

•  Endocarditis

REFERENCES

1.  Uhlemann AC, Dordel J, Knox JR, et al. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc Natl Acad Sci U S A. 2014;111(18):6738–6743.

2.  Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10–e52.

3.  Mistry RD. Skin and soft tissue infections. Pediatr Clin North Am. 2013;60(5):1063–1082.

4.  Singer AJ, Talan DA. Management of skin abscesses in the era of methicillin-resistant Staphylococcus aureus. N Engl J Med. 2014;370(11):1039–1047.

5.  Chambers HF. Pharmacology and the treatment of complicated skin and skin-structure infections. N Engl J Med. 2014;370(23):2238–2239.

ADDITIONAL READING

•  Amin AN, Cerceo EA, Deitelzweig SB, et al. Hospitalist perspective on the treatment of skin and soft tissue infections. Mayo Clin Proc. 2014;89(10):1436–1451.

•  Fenster DB, Renny MH, Ng C, et al. Scratching the surface: a review of skin and soft tissue infections in children. Curr Opin Pediatr. 2015;27(3):303–307.

•  Gurusamy KS, Koti R, Toon CD, et al. Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds. Cochrane Database Syst Rev. 2013;(8):CD009726.

•  Holmes NE, Howden BP. What’s new in the treatment of serious MRSA infection? Curr Opin Infect Dis. 2014;27(6):471–478.

•  Ramakrishnan K, Salinas RC, Agudelo Higuita NI. Skin and soft tissue infections. Am Fam Physician. 2015;92(6):474–483.

 CODES

ICD10

•  A49.02 Methicillin resis staph infection, unsp site

•  A41.02 Sepsis due to Methicillin resistant Staphylococcus aureus

•  J15.212 Pneumonia due to Methicillin resistant Staphylococcus aureus

CLINICAL PEARLS

•  Incise and drain abscesses and send purulent material for culture and sensitivity

•  Local susceptibility patterns of CA-MRSA dictate antibiotic treatment. http://www.cdc.gov/mrsa/pdf/Flowchart_pstr.pdf

•  CA-MRSA skin lesions are commonly misidentified as “spider bites.”