What is the recommended treatment for a patient with normal renal function (Creatinine Clearance (CrCl) 120) and an Ommaya (intraventricular catheter) port infection, with cerebrospinal fluid (CSF) positive for Methicillin-sensitive Staphylococcus aureus (MSSA)?

Treatment of MSSA Ommaya Reservoir Infection with Normal Renal Function

Remove the Ommaya reservoir immediately and treat with IV nafcillin 2 grams every 4 hours or cefazolin 2 grams every 8 hours for 4-6 weeks, with consideration for adding rifampin 600 mg daily after blood cultures clear. 1, 2, 3

Device Removal: The Critical First Step

Ommaya reservoir removal is mandatory and should not be delayed until CSF cultures are repeatedly negative. 1

• The IDSA guidelines explicitly state that for CNS shunt infection (which includes Ommaya reservoirs), shunt removal is recommended and it should not be replaced until CSF cultures are repeatedly negative. 1
• A 2014 study of 40 ORRI cases demonstrated that early device removal resulted in significantly shorter hospitalization and antimicrobial treatment durations compared to late removal (p < 0.038). 4
• Medical therapy alone succeeded in only 81.3% of cases in a 2025 study, and the presence of CSF leak or local wound infection was strongly associated with treatment failure (odds ratio 18.3, p < 0.001). 5
• The only exception to immediate removal is when CSF leak/local wound infection is absent AND the patient can receive the standardized multimodal regimen including intraventricular vancomycin—but this is not standard practice for established infections. 5

Antibiotic Selection: MSSA-Specific Therapy

Switch from empiric MRSA coverage to definitive MSSA therapy immediately once susceptibilities confirm methicillin-sensitivity. 3

First-Line Options for MSSA CNS Infection:

• Nafcillin 2 grams IV every 4 hours is the preferred agent, administered slowly over 30-60 minutes to minimize vein irritation. 6, 3
• Cefazolin 2 grams IV every 8 hours is an equally effective alternative with better tolerability and less frequent dosing. 7, 3
• Both agents achieve superior CNS penetration and bactericidal activity against MSSA compared to vancomycin, which has only 1-5% CSF penetration. 1, 2

Why Not Continue Vancomycin for MSSA?

• Vancomycin achieves maximum CSF concentrations of only 2-6 μg/mL even with inflamed meninges, and outcomes with vancomycin monotherapy for CNS infections have been very poor. 1, 2
• A 2025 JAMA review confirmed that once S. aureus susceptibilities are known, MSSA should be treated with cefazolin or an antistaphylococcal penicillin, not vancomycin. 3
• The IDSA guidelines do not recommend vancomycin for MSSA infections when beta-lactams are available. 1

Adjunctive Rifampin Therapy

Add rifampin 600 mg PO/IV once daily after blood cultures clear if concurrent bacteremia is present. 1, 2

• Rifampin achieves 22% CSF penetration with bactericidal concentrations (0.57-1.24 μg/mL), significantly superior to vancomycin. 1, 2
• The IDSA recommends rifampin 600 mg daily or 300-450 mg twice daily as adjunctive therapy for CNS infections (B-III evidence grade). 1, 2
• Critical pitfall: Never start rifampin until bacteremia has cleared, as monotherapy risks rapid resistance development. 1
• For device-related infections without bacteremia, rifampin can be started immediately with the primary antibiotic. 1

Treatment Duration

Treat for a minimum of 4-6 weeks with IV antibiotics after device removal. 1, 2

• For brain abscess, subdural empyema, or spinal epidural abscess: 4-6 weeks of IV therapy. 1, 2
• For meningitis/ventriculitis without abscess: 2 weeks may be sufficient, though 4 weeks is safer for device-related infections. 2
• The median duration in the 2014 ORRI study was 24 days, but this included cases treated without device removal. 4

Monitoring and Source Control

Obtain blood cultures, perform neurosurgical evaluation, and assess for metastatic infection sites. 1, 3

• Blood cultures should be obtained before starting antibiotics, as 7.5-12% of Ommaya infections have concurrent bacteremia. 1
• Neurosurgical evaluation for incision and drainage is recommended if abscess or empyema is present. 1, 2
• Imaging with MRI/CT should be performed to identify metastatic foci such as vertebral osteomyelitis, epidural abscess, or septic emboli. 3
• Repeat CSF cultures should be obtained after device removal to document clearance before considering replacement. 1

Dosing Adjustments for CrCl 120

No dose adjustment is required for nafcillin; standard dosing applies. 6

• Nafcillin FDA labeling explicitly states: "No dosage alterations are necessary for patients with renal dysfunction, including those on hemodialysis." 6
• For cefazolin with CrCl >55 mL/min, full doses (2 grams every 8 hours) should be given. 7
• With supranormal renal function (CrCl 120), consider that drug clearance may be enhanced, but standard dosing remains appropriate as these are serious CNS infections requiring maximal bactericidal activity. 6, 7

Alternative Regimens (If Beta-Lactam Allergy)

If true beta-lactam allergy exists, use vancomycin 15-20 mg/kg IV every 8-12 hours (target trough 15-20 μg/mL) plus rifampin 600 mg daily for 4-6 weeks. 1, 2

• A loading dose of 25-30 mg/kg should be administered for serious CNS infections. 1, 2
• Linezolid 600 mg IV/PO every 12 hours is an alternative with superior CSF penetration (66%) compared to vancomycin. 2, 8
• TMP-SMX 5 mg/kg/dose IV every 8-12 hours may be considered but has a C-III evidence grade (optional recommendation). 1, 2

Common Pitfalls to Avoid

• Delaying device removal: Medical therapy alone has an 18.7% failure rate even with optimal antibiotics. 5
• Continuing vancomycin for MSSA: This provides suboptimal therapy when superior beta-lactams are available. 1, 2, 3
• Starting rifampin with active bacteremia: This risks rapid resistance development. 1
• Inadequate treatment duration: CNS device infections require 4-6 weeks, not the 2 weeks used for simple meningitis. 1, 2
• Missing metastatic foci: One-third of S. aureus bacteremias cause metastatic infection requiring additional source control. 3