What antibiotic is effective against Staphylococcus (Staph) aureus and Escherichia (E) coli?

Antibiotic Selection for Dual Coverage of Staph aureus and E. coli

For infections requiring coverage of both Staphylococcus aureus and Escherichia coli, piperacillin-tazobactam is the most appropriate single-agent choice, providing broad-spectrum activity against both methicillin-susceptible S. aureus (MSSA) and E. coli. 1

Empiric Single-Agent Options

Piperacillin-Tazobactam (Preferred)

• Provides reliable coverage for both MSSA and E. coli in a single agent 1
• Dosing: 3.375 grams IV every 6 hours or 4.5 grams IV every 6-8 hours for adults 1
• Active against methicillin-susceptible S. aureus and most E. coli strains, including many extended-spectrum beta-lactamase (ESBL) producers 1
• Particularly useful in intra-abdominal infections, complicated urinary tract infections, and nosocomial pneumonia where both pathogens may be present 1

First-Generation Cephalosporins (Alternative)

• Cefazolin provides good coverage for MSSA and most community-acquired E. coli 2, 3
• Less effective against hospital-acquired or ESBL-producing E. coli strains 3
• Dosing: 1-2 grams IV every 8 hours for adults 2

Methicillin-Susceptible S. aureus (MSSA) Considerations

Beta-Lactam Agents (First-Line)

• Penicillinase-resistant penicillins (flucloxacillin, dicloxacillin, nafcillin, oxacillin) are the drugs of choice for serious MSSA infections 3, 4
• First-generation cephalosporins (cefazolin, cephalexin) are effective alternatives 2, 3
• These agents are superior to vancomycin for MSSA and should always be preferred when susceptibility is confirmed 2

Alternative Agents for MSSA

• Clindamycin 600 mg IV/PO three times daily (if local resistance <10%) 2, 5, 3
• Avoid cephalosporins in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm, anaphylaxis) 3

Methicillin-Resistant S. aureus (MRSA) Considerations

Parenteral Options

• Vancomycin 30-60 mg/kg/day IV in 2-4 divided doses is first-line for serious MRSA infections 2
• Loading dose of 25-30 mg/kg for seriously ill patients 2
• Linezolid 600 mg IV/PO every 12 hours is an alternative 2
• Daptomycin 6-10 mg/kg/dose IV daily for complicated infections 2
• Teicoplanin 6-12 mg/kg/dose IV every 12 hours for 3 doses, then daily 2

Oral Options for MRSA

• TMP-SMX (trimethoprim-sulfamethoxazole) 160-320/800-1600 mg PO every 12 hours 2, 6
• Doxycycline 100 mg PO every 12 hours (avoid in children <8 years) 2, 6
• Clindamycin 300-450 mg PO every 8 hours (if susceptible) 2, 6

E. coli Coverage

Empiric Coverage

• Most community-acquired E. coli strains are susceptible to first-generation cephalosporins, piperacillin-tazobactam, and fluoroquinolones 1
• Hospital-acquired strains may require broader coverage with piperacillin-tazobactam or carbapenems 1
• Always obtain cultures and adjust therapy based on susceptibility results 6, 5

Clinical Approach Algorithm

1. Determine methicillin susceptibility status:

   • If MSSA confirmed: Use beta-lactam agents (nafcillin, oxacillin, cefazolin, or piperacillin-tazobactam) 2, 3
   • If MRSA confirmed or suspected: Add vancomycin or linezolid to E. coli coverage 2

2. Assess infection severity and site:

   • Skin/soft tissue: May use oral agents if outpatient 2
   • Bacteremia/endocarditis: Requires prolonged IV therapy (4-6 weeks) 2, 4
   • Pneumonia: 7-21 days of therapy 2
   • Osteomyelitis: >6 weeks of therapy 2

3. Consider combination therapy when:

   • MRSA coverage needed alongside gram-negative coverage: Vancomycin + piperacillin-tazobactam or cefepime 2, 1
   • Prosthetic valve endocarditis: Add rifampin and gentamicin 2

Common Pitfalls to Avoid

• Never use vancomycin for MSSA when beta-lactams can be used—vancomycin is inferior 2
• Do not add aminoglycosides to vancomycin for native valve staphylococcal endocarditis—increases renal toxicity without benefit 2
• Avoid using rifampin or fusidic acid as single agents for MRSA—resistance develops rapidly 3, 4
• Do not use tetracyclines in children <8 years of age 2, 6, 5
• Obtain blood cultures before starting antibiotics if systemic symptoms present 6
• Reassess therapy at 48-72 hours and narrow coverage based on culture results 6, 5