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Methicillin Resistant S. Aureus (MRSA) Skin Infections

Stephen A. Martin, MD, EdM and Paul P. Belliveau, PharmD, RPh
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Subject: Methicillin Resistant S. Aureus (MRSA) Skin Infections

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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 otherwise healthy hosts:

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

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

  • The prevalence of CA-MRSA is rapidly increasing in the United States.

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

    • Severe or invasive disease from CA-MRSA is less frequent but can include the following:

      • Necrotizing pneumonia with abscesses

      • Necrotizing fasciitis

      • Septic thrombophlebitis

      • Sepsis

      • Osteomyelitis

  • Although less frequent, HA-MRSA can still cause SSTIs in the community. One study showed no significant difference in hospitalization rates among CA-MRSA, HA-MRSA, and methicillin-sensitive S. aureus (MSSA) infections.

  • System(s) affected: skin, soft tissue

Epidemiology

  • Predominant age: all ages, generally younger

  • Predominant sex: female > male

Incidence

  • 316/100,000/year (2004–2005)

  • 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 admission data indicate a 29% increase in SSTIs from 2000 to 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 USA 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 with CA-MRSA do not have an obvious risk factor.

  • Any antibiotic use 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

  • High prevalence in the community

  • Hospitalization in the past 12 months (although S. aureus can colonize for years)

General Prevention

  • Colonization (particularly of the anterior nares) is a risk factor for subsequent S. aureus infection. It is not yet clear whether this is also the case for CA-MRSA. Oropharyngeal and inguinal colonization are equally prevalent.

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

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

  • Research for a vaccine is underway.

  • CDC guidance for prevention of MRSA in athletic community: 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

  • Increased warmth

  • Tenderness

  • Swelling

  • Fluctuance

  • Infected wound

  • Folliculitis, pustular lesions

  • Appearance like an insect or spider bite

  • Tissue necrosis

Differential Diagnosis

SSTIs due to another cause. 

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].

  • Although CT or MRI may show fascial plane edema in necrotizing fasciitis, do not delay surgical intervention waiting for imaging, particularly in ill patients.

Diagnostic Procedures/Other

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

Treatment

  • A recent guideline recommends antibiotics active against MRSA for patients with carbuncles or abscesses who failed 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 not requiring hospitalization or vancomycin.

  • Initial empirical antibiotic coverage should be based 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 condition (e.g., tinea pedis).

  • Restrict contact if wound cannot be covered.

  • Elevate affected area.

Medication

Alert

For purulent infections, basic principles include surgical drainage and debulking, wound culture, and narrow-spectrum antimicrobials:
  • Successful I&D may have more impact than antibiotics in mild cases for both adults and children.

  • Moist heat may work for small furuncles.

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

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

First Line

CA-MRSA SSTIs: Treat with a 7–14-day course of one of the following agents (duration of therapy depends on severity and clinical response): 
  • Trimethoprim/sulfamethoxazole (TMP-SMX): DS (160 mg TMP and 800 mg of SMX) 1–2 tablet(s) PO BID daily (8–12 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; 2–5 mg/kg/day PO in 1–2 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: 300–450 mg PO QID (30–40 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 (if the test is positive, this shows induced resistance and a new antibiotic should be chosen).

  • 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 of 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 GI absorption.

Second Line

For treatment of severe CA-MRSA SSTIs requiring hospitalization or for HA-MRSA SSTIs, consider 1 of the following: 
  • 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 5–11 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, 10–13 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. 

Inpatient Considerations

Admission Criteria/Initial Stabilization

Consider admission in patients either 
  • Systemically ill (e.g., febrile) with stable comorbidities, or

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

  • Depends on severity of SSTI, presence of SSTI complications (sepsis, necrotizing fasciitis), and comorbidities

Nursing

Contact precautions 

Discharge Criteria

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

  • Keep wounds that are draining covered with clean, dry bandages.

  • Clean hands regularly with soap and water or alcohol-based gel. Hot shower daily with soap.

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

  • Clean clothes, towels, and bed linens.

The CDC has gathered information for health care professionals, including clinical guides, via the National MRSA Education Initiative: www.cdc.gov/mrsa/

Prognosis

  • In outpatients, improvement should occur within 48 hours.

Data are limited as to risk of recurrence. 

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. [View Abstract]
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. D014;59(2):e10–e52.
3.
Mistry  RD. Skin and soft tissue infections. Pediatr Clin North Am.  2013;60(5):1063–1082. doi:10.1016/j.pcl.2013.06.011. [View Abstract]
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. doi:10.1056/NEJMra1212788. [View Abstract]
5.
Chambers  HF. Pharmacology and the treatment of complicated skin and skin-structure infections. N Engl J Med.  2014;370(23):2238–2239. [View Abstract]

Additional Reading

  • Breen  JO. Skin and soft tissue infections in immunocompetent patients. Am Fam Physician.  2010;81(7):893–899. [View Abstract]

  • Chen  LF, Chastain  C, Anderson  DJ. Community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections: management and prevention. Curr Infect Dis Rep.  2011;13(5):442–450. [View Abstract]

  • Chuck  EA, Frazee  BW, Lambert  L, et al. The benefit of empiric treatment for methicillin-resistant Staphylococcus aureus. J Emerg Med.  2010;38(5):567–571. [View Abstract]

  • Dryden  MS. Complicated skin and soft tissue infection. J Antimicrob Chemother.  2010;65(Suppl 3):iii35–iii44. [View Abstract]

  • Fitch  MT, Manthey  DE, McGinnis  HD, et al. Videos in clinical medicine. Abscess incision and drainage. N Engl J Med.  2007;357(19):e20. doi:10.1056/NEJMvcm071319. [View Abstract]

  • 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. [View Abstract]

Codes

ICD10

  • L08.89 Oth local infections of the skin and subcutaneous tissue

  • A49.02 Methicillin resis staph infection, unsp site

  • Z22.322 Carrier or suspected carrier of methicillin resis staph

ICD09

  • 686.8 Other specified local infections of skin and subcutaneous tissue

  • 041.12 Methicillin resistant Staphylococcus aureus in conditions classified elsewhere and of unspecified site

  • V02.54 Carrier or suspected carrier of Methicillin resistant Staphylococcus aureus

SNOMED

  • 108365000 infection of skin (disorder)

  • 266096002 methicillin resistant Staphylococcus aureus infection (disorder)

  • 432415000 methicillin resistant staphylococcus aureus carrier (finding)

Clinical Pearls

  • Incise and drain purulent lesions and send for wound culture if abscess is present.

  • Prevalence and susceptibilities of CA-MRSA dictates treatment in different location. The CDC has a helpful algorithm for outpatient treatment of CA-MRSA: http://www.cdc.gov/mrsa/pdf/Flowchart_pstr.pdf.

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

 
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