What is the treatment for MSSA bacteremia with piperacillin/tazobactam?

Treatment of MSSA Bacteremia: Piperacillin/Tazobactam Is Not Recommended as Definitive Therapy

For definitive treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, piperacillin/tazobactam should NOT be used as monotherapy; instead, treatment should be de-escalated to nafcillin, oxacillin, or cefazolin once susceptibilities are known. 1, 2

First-Line Treatment Options for MSSA Bacteremia

• Nafcillin or oxacillin is the preferred first-line agent for MSSA bacteremia, with a recommended duration of 6 weeks for uncomplicated left-sided infective endocarditis (IE) and at least 6 weeks for complicated IE 3
• Cefazolin is an acceptable alternative to nafcillin/oxacillin in patients with non-severe penicillin allergies 1
• Piperacillin/tazobactam is associated with significantly higher mortality compared to nafcillin/oxacillin/cefazolin when used as monotherapy for MSSA bacteremia (HR 0.10; 95% CI, 0.01-0.78) 2

Clinical Scenarios and Treatment Algorithms

Initial Empiric Therapy

• Piperacillin/tazobactam may be appropriate for initial empiric coverage when:
  • Polymicrobial infection is suspected (including both gram-negative and anaerobic organisms) 1
  • The patient has risk factors for healthcare-associated infections 1

Definitive Therapy After Culture Results

• Once MSSA is identified in blood cultures:
  • De-escalate to nafcillin, oxacillin, or cefazolin 1, 2
  • Avoid continuing piperacillin/tazobactam as monotherapy for MSSA bacteremia 2
  • For patients with severe penicillin allergies, vancomycin or daptomycin should be used 3, 4

Special Considerations

• In cases of MSSA bacteremia with brain abscess, nafcillin is preferred over cefazolin due to better blood-brain barrier penetration 3
• For patients with right-sided IE, gentamicin should not be added to beta-lactam therapy (Class III; Level of Evidence B) 3

Evidence Quality and Comparative Effectiveness

• Multiple studies demonstrate that antistaphylococcal penicillins (nafcillin/oxacillin) and cefazolin have similar efficacy for MSSA bacteremia 5, 6
• A national cohort study of veterans with MSSA bacteremia showed no significant difference in 30-day mortality between nafcillin/oxacillin and cefazolin (HR, 0.67; 95% CI, 0.11-4.00) 2
• The same study demonstrated significantly higher mortality with piperacillin/tazobactam compared to nafcillin/oxacillin/cefazolin 2

Common Pitfalls and Caveats

• Piperacillin/tazobactam is not FDA-approved for MSSA bacteremia; its indications include intra-abdominal infections, nosocomial pneumonia, skin and skin structure infections, female pelvic infections, and community-acquired pneumonia 7
• Continuing broad-spectrum therapy like piperacillin/tazobactam when a narrower agent would be effective contributes to antimicrobial resistance 1
• Once-daily antibiotic regimens (like ceftriaxone) are not recommended for MSSA bacteremia despite their convenience 8
• The inoculum effect with cefazolin (decreased efficacy at high bacterial loads) may be a concern in some deep-seated infections, but can be mitigated with aggressive dosing 6

Duration of Therapy

• For uncomplicated MSSA bacteremia: minimum 2 weeks of therapy 4
• For complicated infections (endocarditis, osteomyelitis, etc.): 4-6 weeks of therapy 3
• For left-sided IE: 6 weeks of therapy is recommended 3