What is the appropriate outpatient coverage for Methicillin-resistant Staphylococcus aureus (MRSA)?

From the Guidelines

For outpatient MRSA coverage, the first-line treatment is typically oral trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim) at a dose of 1-2 double-strength tablets (160mg/800mg) twice daily for 7-14 days, depending on infection severity. Alternative options include clindamycin 300-450mg orally four times daily, doxycycline 100mg twice daily, or minocycline 100mg twice daily for the same duration 1. Linezolid 600mg twice daily is effective but expensive and reserved for severe cases or treatment failures. For skin infections, adding wound care with incision and drainage is essential when abscesses are present. Patients should complete the full course of antibiotics even if symptoms improve quickly. MRSA coverage is important for skin and soft tissue infections in areas with high MRSA prevalence, in patients with previous MRSA infections, healthcare workers, or those with recent antibiotic exposure. These medications target MRSA by different mechanisms - TMP-SMX inhibits bacterial folate synthesis, tetracyclines inhibit protein synthesis, and clindamycin blocks bacterial ribosomal function. Resistance patterns vary geographically, so local antibiogram data should guide therapy when available.

Some key points to consider:

• Incision and drainage is the primary treatment for cutaneous abscesses, and antibiotic therapy may be recommended for abscesses associated with severe or extensive disease, systemic illness, or lack of response to incision and drainage alone 1.
• Empirical therapy for CA-MRSA is recommended for outpatients with purulent cellulitis, and options include clindamycin, TMP-SMX, doxycycline, minocycline, and linezolid 1.
• For outpatients with nonpurulent cellulitis, empirical therapy for b-hemolytic streptococci is recommended, and options include b-lactam antibiotics, clindamycin, or linezolid 1.
• Cultures from abscesses and other purulent SSTIs are recommended in patients treated with antibiotic therapy, patients with severe local infection or signs of systemic illness, patients who have not responded adequately to initial treatment, and if there is concern for a cluster or outbreak 1.

From the FDA Drug Label

Cure Rates at the Test-of-Cure Visit for Microbiologically Evaluable Adult Patients with Complicated Skin and Skin Structure Infections Pathogen Cured ZYVOXn/N (%) Oxacillin/Dicloxacillinn/N (%) Staphylococcus aureus 73/83 (88) 72/84 (86) Methicillin-resistant S aureus 2/3 (67) 0/0 (-)

The cure rates in microbiologically evaluable patients with MRSA skin and skin structure infection were 26/33 (79%) for linezolid-treated patients and 24/33 (73%) for vancomycin-treated patients

Outpatient MRSA coverage can be achieved with linezolid (ZYVOX), which has shown cure rates of 79% in microbiologically evaluable patients with MRSA skin and skin structure infections, as compared to vancomycin which had a cure rate of 73% 2.

• Key points:
  • Linezolid is effective against MRSA
  • Cure rates for linezolid are comparable to vancomycin
  • Linezolid can be used for outpatient treatment of MRSA infections

From the Research

Outpatient MRSA Coverage

• The choice of empirical therapy for MRSA infections should be based on the site and severity of the infection 3.
• For moderate skin and soft tissue infections, oral antibiotics such as trimethoprim-sulfamethoxazole, clindamycin, doxycycline/minocycline, and linezolid can be used in the outpatient setting 3.
• Minocycline is often preferred over trimethoprim-sulfamethoxazole or doxycycline for the treatment of community-acquired MRSA skin and soft-tissue infections 4.
• Other oral anti-staphylococcal agents that may have utility in the treatment of skin and soft tissue infections include clindamycin, trimethoprim-sulfamethoxazole, doxycycline, rifampin, moxifloxacin, and minocycline, but the clinical data for their efficacy is limited 5.
• There is limited evidence to support the use of trimethoprim-sulfamethoxazole, clindamycin, doxycycline, or minocycline in the treatment of MRSA pneumonia, and randomized controlled trials are required to determine their effectiveness 6.
• A study found that patients with MRSA skin and soft tissue infections treated with a higher dose of trimethoprim-sulfamethoxazole (320 mg/1,600 mg twice daily) had a similar rate of clinical resolution as patients treated with the standard dose (160 mg/800 mg twice daily) 7.

Treatment Options

• Vancomycin is a standard empiric choice for severe/invasive MRSA infections, but alternative therapies such as linezolid, daptomycin, and ceftaroline exist 3, 5.
• Linezolid is probably the drug of choice for the treatment of complicated MRSA skin and soft tissue infections, but its use in pneumonia is debatable 5.
• Daptomycin has shown to be non-inferior to vancomycin in the treatment of staphylococcal skin and soft tissue infections, bacteremia, and right-sided endocarditis 5.
• Ceftaroline is a broad-spectrum cephalosporin with activity against MRSA and is non-inferior to vancomycin in the treatment of skin and soft tissue infections 5.