Which of the following agents may be used to treat infections caused by methicillin‑resistant Staphylococcus aureus (MRSA): vancomycin, linezolid, penicillin, cephalosporin, rifampicin?

Treatment Options for MRSA Infections

For MRSA infections, vancomycin, linezolid, and rifampicin (in combination) are appropriate treatment options, while penicillin and cephalosporins are NOT effective. 1

Effective Anti-MRSA Agents

Vancomycin (Option A: CORRECT)

• Vancomycin remains the primary recommended agent for serious MRSA infections, including bacteremia, endocarditis, pneumonia, and complicated skin/soft tissue infections 1
• Dosing: 30-60 mg/kg/day IV divided every 6-12 hours (loading dose of 25-30 mg/kg for seriously ill patients) 1
• Duration varies by infection type: 7-14 days for uncomplicated bacteremia, 4-6 weeks for complicated bacteremia or endocarditis 1

Linezolid (Option B: CORRECT)

• Linezolid 600 mg IV/PO every 12 hours is recommended as an alternative first-line agent for MRSA infections 1
• Particularly effective for pneumonia (A-II recommendation) and skin/soft tissue infections (A-II recommendation) 1
• Advantages include excellent oral bioavailability and tissue penetration 2
• Monitor complete blood counts weekly, especially for treatment exceeding 2 weeks due to thrombocytopenia risk 3
• Treatment duration: 7-21 days for pneumonia, 7-14 days for uncomplicated bacteremia 3

Rifampicin (Option E: CORRECT with caveats)

• Rifampicin should NEVER be used as monotherapy for MRSA due to rapid resistance development 4
• Appropriate only in combination regimens: rifampicin 300-600 mg daily PLUS vancomycin or another anti-MRSA agent 1
• Specific indications include prosthetic valve endocarditis (rifampicin + vancomycin + gentamicin for 6 weeks) and osteomyelitis (after bacteremia clearance) 1
• The FDA label confirms rifampicin has in vitro activity against MRSA, but clinical use requires combination therapy 5

Ineffective Agents for MRSA

Penicillin (Option C: INCORRECT)

• Penicillin has NO activity against MRSA and should never be used 4
• MRSA is defined by resistance to all beta-lactam antibiotics, including penicillins 1
• Even penicillinase-resistant penicillins (flucloxacillin, dicloxacillin) are ineffective against MRSA 4

Cephalosporins (Option D: INCORRECT - with one exception)

• Standard cephalosporins (cefazolin, cephalexin, ceftriaxone) are NOT effective against MRSA 4
• MRSA resistance mechanisms confer cross-resistance to all traditional cephalosporins 1
• Exception: Ceftaroline (5th generation cephalosporin) has anti-MRSA activity due to affinity for PBP2a, but this is NOT a standard cephalosporin 6, 2

Clinical Decision Algorithm

For hospitalized patients with confirmed MRSA:

1. Start vancomycin 30-60 mg/kg/day IV (loading dose if severely ill) 1
2. Consider linezolid 600 mg IV/PO q12h if: pneumonia present, vancomycin allergy, or renal dysfunction 1
3. Add rifampicin only for: prosthetic valve endocarditis, osteomyelitis (after bacteremia clears), or persistent bacteremia 1

For outpatient MRSA skin infections:

• Linezolid 600 mg PO q12h (if severe) 1
• Alternative oral options: clindamycin 600 mg q8h (if susceptible), doxycycline, or TMP-SMX 1

Critical Pitfalls to Avoid

• Never use rifampicin alone - resistance emerges within days 4
• Do not assume cephalosporins work for MRSA - only ceftaroline (not listed as a standard option) has activity 6
• Avoid linezolid for >2 weeks without hematologic monitoring - significant thrombocytopenia risk (RR 13.06 vs vancomycin) 7, 3
• Penicillins are completely ineffective - MRSA definition includes penicillin resistance 4