Treatment of Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia with Cloxacillin
Cloxacillin is a first-line treatment for MSSA bacteremia, administered at 12 g/day intravenously in 4-6 divided doses for 4-6 weeks, with superior efficacy compared to vancomycin and other alternatives. 1
First-Line Treatment Options for MSSA Bacteremia
- Antistaphylococcal beta-lactams (cloxacillin, oxacillin, nafcillin) are the preferred agents for MSSA bacteremia due to their superior efficacy compared to vancomycin 2
- For MSSA bacteremia, cloxacillin should be administered at 12 g/day intravenously in 4-6 doses for 4-6 weeks depending on the severity and presence of complications 1
- In severe staphylococcal infections, therapy with cloxacillin/oxacillin should be continued for at least 14 days, and at least 48 hours after the patient becomes afebrile, asymptomatic, and cultures are negative 3
- For endocarditis and osteomyelitis, a longer duration of therapy (4-6 weeks) is required 3
Alternative Treatment Options
- Cefazolin (1-2g IV every 8 hours) is an acceptable alternative to cloxacillin for MSSA bacteremia with similar efficacy 2, 4
- For patients with confirmed severe beta-lactam allergy, daptomycin should be chosen where available, given in combination with another effective antistaphylococcal drug 1
- Vancomycin is inferior to beta-lactams for MSSA bacteremia and should only be used when beta-lactams cannot be administered 1, 2
Special Clinical Scenarios
- For uncomplicated right-sided native valve MSSA infective endocarditis, short-term (2-week) treatments have been proposed, but these regimens cannot be applied to left-sided IE 1
- In hemodialysis patients with MSSA bacteremia, cefazolin dosed during HD sessions has shown comparable efficacy to cloxacillin with shorter length of stay and lower costs 5
- For patients with penicillin allergy, penicillin desensitization can be attempted in stable patients since vancomycin is inferior to beta-lactams 1
Monitoring and Follow-up
- Follow-up blood cultures should be obtained 2-4 days after initial positive cultures to document clearance of bacteremia 2
- Echocardiography is recommended for all adult patients with S. aureus bacteremia to rule out endocarditis 2, 6
- Prolonged S. aureus bacteremia (≥48 hours) is associated with a 90-day mortality risk of 39% and requires thorough evaluation for metastatic foci of infection 6
Important Clinical Pearls
- The addition of aminoglycosides in staphylococcal native valve IE is no longer recommended due to increased renal toxicity without improved outcomes 1
- Recent research has shown that combination therapy with cloxacillin plus fosfomycin did not achieve better treatment success at day 7 compared to cloxacillin alone in MSSA bacteremia 7
- Source control is a critical component of treating S. aureus bacteremia and may include removal of infected intravascular devices, drainage of abscesses, and surgical debridement 6
- Cephalotin has shown similar efficacy to dicloxacillin for MSSA bacteremia in settings where first-line agents are unavailable 8