What is the treatment approach for skin infections with concern for Methicillin-resistant Staphylococcus aureus (MRSA)?

Treatment of Skin Infections with Concern for MRSA

Initial Management: Drainage First

For any abscess or purulent collection, incision and drainage is the cornerstone of therapy and should be performed whenever feasible, often sufficient alone for simple abscesses without antibiotics 1.

• Obtain cultures from purulent drainage before starting antibiotics to confirm MRSA and guide definitive therapy 2.
• Simple abscesses or boils may require only incision and drainage without antibiotics 1.

When to Add Antibiotics After Drainage

Add antibiotic therapy if any of the following are present 1:

• Severe or extensive disease (multiple sites) or rapid progression with associated cellulitis
• Signs of systemic illness (fever, tachycardia, hypotension)
• Comorbidities or immunosuppression (diabetes, HIV/AIDS, malignancy)
• Extremes of age
• Abscess in difficult-to-drain locations (face, hand, genitalia)
• Associated septic phlebitis
• Lack of response to incision and drainage alone

Outpatient Oral Antibiotic Selection

For Purulent Cellulitis (MRSA Coverage Required)

Clindamycin 300-450 mg PO three times daily is the preferred first-line option as it provides coverage for both MRSA and beta-hemolytic streptococci as a single agent 1, 2.

Alternative options include:

• TMP-SMX 1-2 double-strength tablets PO twice daily - highly effective for MRSA but does NOT reliably cover beta-hemolytic streptococci 1, 2.
• Doxycycline 100 mg PO twice daily - effective for MRSA but streptococcal coverage uncertain 1, 2.
• Minocycline 200 mg once, then 100 mg PO twice daily - may be more reliable than doxycycline or TMP-SMX when these fail 1, 3.
• Linezolid 600 mg PO twice daily - highly effective but significantly more expensive than alternatives 1, 2.

Critical caveat: When using TMP-SMX, doxycycline, or minocycline, consider adding a beta-lactam (amoxicillin 500 mg PO three times daily) if streptococcal infection cannot be excluded, as these agents have unreliable activity against beta-hemolytic streptococci 1.

For Non-Purulent Cellulitis

• Start with a beta-lactam alone (cephalexin 500 mg PO four times daily or dicloxacillin 500 mg PO four times daily) for empirical coverage of beta-hemolytic streptococci 1.
• Add MRSA coverage (clindamycin or TMP-SMX) if the patient fails to respond to beta-lactam therapy within 48-72 hours or has systemic toxicity 1.

Pediatric Dosing

• Clindamycin 10-13 mg/kg/dose PO every 6-8 hours (maximum 40 mg/kg/day) 1, 2.
• TMP-SMX: trimethoprim 4-6 mg/kg/dose PO every 12 hours - contraindicated in children <2 months and third-trimester pregnancy 1.
• Doxycycline 2 mg/kg/dose PO every 12 hours for children <45 kg - avoid in children <8 years of age 1.
• Linezolid 10 mg/kg/dose PO every 8 hours (maximum 600 mg/dose) 1.

Treatment Duration

• 5-10 days for uncomplicated MRSA skin infections 2, 4.
• 7-14 days for complicated infections 2, 4.
• Reassess clinically within 48-72 hours to ensure appropriate response 2.

Hospitalization and IV Therapy

Admit for IV antibiotics when 1, 4:

• Systemic toxicity or rapidly progressive infection despite appropriate oral antibiotics
• Penetrating trauma, injection drug use, or SIRS criteria met
• Prior MRSA colonization/infection with severe presentation

IV Antibiotic Options

• Vancomycin 15-20 mg/kg/dose IV every 8-12 hours is first-line for hospitalized patients 1, 2, 4.
• Linezolid 600 mg IV/PO twice daily - equivalent efficacy to vancomycin for MRSA skin infections with cure rate of 79% 1, 5.
• Daptomycin 4 mg/kg/dose IV daily - FDA-approved for complicated skin and skin structure infections caused by MRSA 6.

For severe cellulitis requiring both MRSA and broad Gram-negative coverage, use vancomycin plus piperacillin-tazobactam 4.

Critical Pitfalls to Avoid

• Never use beta-lactam antibiotics alone when MRSA is suspected - they have zero activity against MRSA 4, 7.
• Never use rifampin as monotherapy or adjunctive therapy for skin infections - resistance develops rapidly and no benefit demonstrated 1, 7.
• Do not use TMP-SMX or tetracyclines alone for non-purulent cellulitis - they will miss streptococcal coverage, the most common cause of typical cellulitis 4, 7.
• Clindamycin resistance testing is essential - inducible clindamycin resistance should preclude its use in serious infections 1.
• Failure to drain abscesses leads to treatment failure regardless of antibiotic choice 4, 7.
• Clostridium difficile-associated disease occurs more frequently with clindamycin compared to other oral agents 1.

Special Populations

• Pregnancy: TMP-SMX is category C/D and contraindicated in third trimester; tetracyclines are category D and contraindicated 1.
• Children <8 years: avoid tetracyclines due to tooth discoloration 1, 2.
• Children <2 months: avoid TMP-SMX 1.