What two oral antibiotics should be used to cover both Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas infections?

Oral Antibiotics for Dual MRSA and Pseudomonas Coverage

Trimethoprim-sulfamethoxazole (TMP-SMX) is the only reliable single oral agent that provides coverage against both MRSA and Pseudomonas, making it the primary choice for dual coverage. 1

Primary Recommendation: TMP-SMX as Monotherapy

For infections requiring coverage of both MRSA and Pseudomonas, TMP-SMX (1-2 double-strength tablets twice daily) should be used as first-line therapy. 1 This recommendation is based on:

• TMP-SMX is the only oral antibiotic with documented activity against both pathogens 1
• The Infectious Diseases Society of America identifies TMP-SMX as the most effective single agent for dual coverage 1
• Clinical studies demonstrate high cure rates for MRSA skin and soft tissue infections with TMP-SMX 2
• TMP-SMX has established efficacy against Pseudomonas species, though activity may be variable 1

Alternative: Combination Therapy When Single Agent Insufficient

If TMP-SMX alone is inadequate or contraindicated, use a fluoroquinolone (ciprofloxacin or levofloxacin) for Pseudomonas coverage combined with a second agent for MRSA coverage. 3, 1

Specific Combination Options:

Option 1: Ciprofloxacin + Doxycycline

• Ciprofloxacin 500-750mg twice daily provides Pseudomonas coverage 3
• Doxycycline 100mg twice daily provides MRSA coverage 3
• This combination addresses both pathogens with bactericidal activity against Pseudomonas 2

Option 2: Levofloxacin + Minocycline

• Levofloxacin 500-750mg daily for Pseudomonas 1
• Minocycline 100mg twice daily for MRSA 3
• Minocycline has demonstrated effectiveness in clinical studies for MRSA infections 2

Critical Limitations of Other Oral Agents

The following commonly used MRSA antibiotics have NO activity against Pseudomonas and should NOT be used for dual coverage:

• Linezolid (600mg twice daily): Excellent MRSA coverage but limited activity against Pseudomonas 1
• Clindamycin (300-450mg three times daily): Effective for some MRSA but completely ineffective against Pseudomonas, with high MRSA resistance rates up to 50% 3, 1
• Cephalexin and other oral cephalosporins: No Pseudomonas coverage 3

Important Clinical Caveats

Monitor for TMP-SMX adverse effects including:

• Hyperkalemia 1
• Bone marrow suppression 1
• Rash and hypersensitivity reactions 1
• Dose adjustment required in renal insufficiency 1

Fluoroquinolone considerations:

• Extended use should be discouraged due to selective pressure for ESBL-producing Enterobacteriaceae and MRSA 3
• Resistance rates to fluoroquinolones are rising, particularly among E. coli and other Enterobacteriaceae 3
• Should be reserved for patients with beta-lactam allergies or when other options are unavailable 3

Tetracycline restrictions:

• Should not be used in children under 8 years of age 3
• Pregnancy category D 3
• Variable activity against Pseudomonas 1

Severe Infections Requiring Enhanced Coverage

For severe infections (bacteremia, pneumonia) involving both organisms, consider combination therapy with TMP-SMX plus minocycline or higher doses of TMP-SMX. 1 The Infectious Diseases Society of America recommends this approach for enhanced dual coverage in critically ill patients 1.

Consult local antibiogram data before finalizing therapy, as resistance patterns vary significantly by institution and geographic region. 1