Does Vancomycin Cover MSSA?
Vancomycin does provide microbiologic coverage for MSSA, but it is clinically inferior and should not be used as definitive therapy when beta-lactams (nafcillin, oxacillin, or cefazolin) can be given. 1, 2
Why Vancomycin is Inferior for MSSA
Beta-lactams demonstrate 35-43% lower mortality compared to vancomycin for definitive treatment of MSSA bloodstream infections, with the strongest benefit seen with antistaphylococcal penicillins (nafcillin/oxacillin) or cefazolin 2
The American Heart Association's meta-analysis showed that β-lactam–containing regimens are superior to vancomycin monotherapy for bacteremic MSSA infections, including infective endocarditis 3
Even when vancomycin is de-escalated to beta-lactams after susceptibility results return, outcomes remain inferior compared to starting with beta-lactams empirically 4
Vancomycin has limited bactericidal activity, poor tissue penetration into vegetations, and overall worse outcomes for MSSA infections 5
When Vancomycin is Acceptable for MSSA
Vancomycin should only be used for MSSA in these specific circumstances:
True immediate-type (anaphylactoid) hypersensitivity to all beta-lactams where desensitization is not feasible 1, 5
CNS/spinal infections where nafcillin cannot be tolerated (nafcillin is required for adequate blood-brain barrier penetration; cefazolin is inadequate) 3, 1
The American Heart Association gives vancomycin a Class I recommendation only as an alternative when nafcillin cannot be tolerated for brain abscess complicating MSSA bacteremia 3, 1
Empiric vs. Definitive Therapy
For empiric therapy (before susceptibilities known): Vancomycin combined with an antistaphylococcal beta-lactam shows similar mortality to vancomycin alone, though the benefit of combination therapy remains uncertain 3, 2, 4
For definitive therapy (after MSSA confirmed): Switch immediately to beta-lactams—continuing vancomycin "because the patient is doing well" increases mortality risk 1, 2
Preferred Beta-Lactam Agents for MSSA
The hierarchy of preferred agents once MSSA is confirmed:
- Nafcillin or oxacillin 2g IV every 4-6 hours (first-line for serious infections) 1, 6
- Cefazolin 2g IV every 8 hours (acceptable for non-severe penicillin allergies, but NOT for CNS infections) 1, 6
Critical Pitfalls to Avoid
Never continue vancomycin for MSSA once susceptibilities confirm methicillin-susceptibility—this is associated with 2-3 times the risk of morbidity and mortality 4
Never use cefazolin for CNS/spinal MSSA infections—inadequate CNS penetration leads to treatment failure; nafcillin must be used 1
Do not add gentamicin to beta-lactam therapy for MSSA—the American Heart Association gives this a Class III recommendation due to increased nephrotoxicity without mortality benefit 1, 6