Management of Persistent MSSA Bacteremia Without Identifiable Source
For persistent MSSA bacteremia with no identifiable source, immediately pursue aggressive diagnostic imaging (urgent MRI, TEE) to identify occult deep-seated infection, continue antistaphylococcal beta-lactam therapy (nafcillin/oxacillin 2g IV q4h or cefazolin 2g IV q8h) for 4-6 weeks, and consider adding daptomycin 8-10 mg/kg IV daily as salvage combination therapy if bacteremia persists beyond 72 hours despite adequate beta-lactam therapy. 1, 2
Immediate Diagnostic Workup
Obtain urgent MRI of the spine and pelvis to identify deep-seated infections such as vertebral osteomyelitis, epidural abscess, or psoas abscess, as inadequate source control is the most common cause of persistent bacteremia 1, 3
Perform transesophageal echocardiography (TEE) immediately rather than transthoracic echo, as TEE is superior for detecting vegetations, intracardiac abscesses, and valvular complications in persistent bacteremia 4, 3
Obtain repeat blood cultures every 48-72 hours until clearance is documented, as prolonged bacteremia ≥48 hours is associated with 39% 90-day mortality 4, 3
Consider CT imaging of chest, abdomen, and pelvis to identify metastatic foci including splenic abscess, septic pulmonary emboli, or occult abdominal collections 3
Antibiotic Management
First-Line Therapy
Continue nafcillin or oxacillin 2g IV every 4 hours as the preferred agent for MSSA bacteremia, as beta-lactams are superior to vancomycin for MSSA 1, 5
Cefazolin 2g IV every 8 hours is an acceptable alternative with equivalent efficacy to antistaphylococcal penicillins 1, 6
Nafcillin is explicitly superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for MSSA, with vancomycin therapy being significantly associated with relapse by multivariate analysis 5
Salvage Combination Therapy for Persistent Bacteremia
If bacteremia persists beyond 72 hours despite adequate beta-lactam therapy and no source is identified, add daptomycin 8-10 mg/kg IV daily to the existing beta-lactam 2, 7
The combination of daptomycin plus oxacillin achieved median blood culture clearance of 2 days in patients with persistent MSSA bacteremia (median duration 7.8 days prior to combination), with 100% microbiological cure 2
Alternative salvage option is oxacillin plus ertapenem, which led to blood culture clearance in a median of 1 day among patients with persistent MSSA bacteremia, though this is not carbapenem-sparing 7
Do NOT add gentamicin or rifampin to beta-lactam therapy, as these combinations do not improve outcomes and increase toxicity 4, 1
Duration of Therapy
For uncomplicated bacteremia (defined as: exclusion of endocarditis, no implanted prostheses, blood cultures negative by days 2-4, defervescence within 72 hours, no metastatic infection): minimum 2 weeks of IV therapy 4
For complicated bacteremia (persistent bacteremia, delayed clearance, or any concern for deep-seated infection even if not yet identified): 4-6 weeks of IV therapy 4, 1
If endocarditis is identified: 6 weeks of IV therapy from the date of first negative blood culture 4, 1
Critical Pitfalls to Avoid
Do not use vancomycin for MSSA unless there is documented severe beta-lactam allergy, as vancomycin has demonstrably worse outcomes and higher relapse rates 1, 6, 5
Do not switch antibiotics within the first 72 hours unless clinical deterioration occurs or MIC testing reveals resistance 8
Do not assume "no source" without comprehensive imaging, as metastatic infection occurs in >33% of S. aureus bacteremia cases and includes vertebral osteomyelitis (4%), epidural abscess, and other occult foci 3
Failure to remove infected intravascular devices/catheters is a common factor in patients experiencing multiple relapses 5
Do not rely on transthoracic echo alone in persistent bacteremia, as TEE is required to adequately exclude endocarditis 4, 3
Monitoring for Treatment Failure
If bacteremia persists beyond 72 hours despite appropriate antibiotics, repeat MIC susceptibility testing of the isolate using standardized procedures, as failure may be due to reduced susceptibility 8
Obtain spine MRI and repeat TEE if persistent bacteremia continues, as sequestered foci of infection must be ruled out 1, 8
Consider surgical consultation for potential debridement or device removal even if no obvious source is identified, as occult infected material may be present 4, 8