What antibiotics are effective against Methicillin-Sensitive Staphylococcus Aureus (MSSA), Pseudomonas, and Enterococcus?

Antibiotic Selection for MSSA, Pseudomonas, and Enterococcus

For proven MSSA infections, use nafcillin, oxacillin, or cefazolin as first-line therapy; for Pseudomonas, use antipseudomonal beta-lactams (piperacillin-tazobactam, cefepime, ceftazidime, or carbapenems); and for Enterococcus faecalis, use ampicillin or penicillin for susceptible isolates. 1, 2, 3

MSSA Treatment

Beta-lactams are superior to all alternatives for MSSA infections:

• Nafcillin or oxacillin (2g IV every 6 hours) are the preferred agents for proven MSSA infections 1, 2
• Cefazolin (1-2g IV every 8 hours) is an equally effective alternative and may be preferred in some settings 2, 4, 5
• Flucloxacillin (2g IV every 6 hours) is equivalent to nafcillin/oxacillin where available 2

For severe beta-lactam allergies:

• Vancomycin (15-20 mg/kg IV every 8-12 hours) is the alternative, though inferior to beta-lactams 2, 4, 5
• Daptomycin is preferred over vancomycin when available for beta-lactam allergic patients 4

Critical pitfall: Never use vancomycin for MSSA when beta-lactams can be used—beta-lactams have superior outcomes 2, 4, 5

Pseudomonas Treatment

Antipseudomonal beta-lactams are the foundation of therapy:

• Piperacillin-tazobactam (4.5g IV every 6 hours or extended infusion) provides broad coverage including Pseudomonas 1, 3
• Ceftazidime (2g IV every 8 hours) has excellent Pseudomonas activity 6
• Cefepime, meropenem, or imipenem are alternative antipseudomonal agents 1

For high-risk patients or structural lung disease (bronchiectasis, cystic fibrosis):

• Use two antipseudomonal agents from different classes 1
• Do NOT use aminoglycosides as the sole antipseudomonal agent 1

Risk factors requiring dual coverage include:

• Prior IV antibiotic use within 90 days 1
• Septic shock or need for ventilatory support 1
• Structural lung disease 1

Enterococcus Treatment

Ampicillin-susceptible Enterococcus faecalis:

• Ampicillin or penicillin are the drugs of choice for susceptible isolates 3
• Piperacillin-tazobactam has activity against ampicillin-susceptible E. faecalis 3

Important limitation: These recommendations apply only to ampicillin/penicillin-susceptible Enterococcus faecalis—vancomycin-resistant enterococcus (VRE) and E. faecium require different approaches 3

Combination Coverage Scenarios

When empiric coverage for all three organisms is needed:

• Piperacillin-tazobactam (4.5g IV every 6 hours) provides coverage for MSSA, Pseudomonas, and ampicillin-susceptible Enterococcus 3
• This single agent covers all three pathogens in most clinical scenarios 3

For high-risk Pseudomonas scenarios requiring dual coverage:

• Add an aminoglycoside (gentamicin or tobramycin) or a fluoroquinolone (ciprofloxacin) to piperacillin-tazobactam 1
• Alternatively, combine piperacillin-tazobactam with cefepime or an aminoglycoside 1

Critical consideration: If MSSA coverage is omitted from empiric therapy (e.g., using aztreonam for severe penicillin allergy), you must add specific MSSA coverage with vancomycin or another agent 1

Duration and Monitoring

Treatment duration depends on infection type:

• Uncomplicated bacteremia: minimum 2 weeks 2
• Complicated bacteremia: 4-6 weeks 2, 4
• Endocarditis: 6 weeks 2, 4

Obtain follow-up blood cultures 2-4 days after initial positive cultures to document clearance 2, 4, 5

Key Clinical Pitfalls

• Never add rifampin or gentamicin to beta-lactam monotherapy for MSSA bacteremia—this increases adverse events without improving outcomes 2, 7
• Combination therapy for MSSA does not reduce mortality and increases adverse events 7
• Aminoglycosides should not be added to flucloxacillin/nafcillin as they increase nephrotoxicity without benefit 2
• Always switch from empiric vancomycin to beta-lactams once MSSA is confirmed 2, 4, 5