In an adult with acute bacterial meningitis requiring vancomycin, how should the dose be adjusted based on creatinine clearance, what target trough concentration should be achieved, and what alternative agents are recommended for a severe vancomycin allergy?

Vancomycin Dosing in Acute Bacterial Meningitis

For acute bacterial meningitis requiring vancomycin, administer 15-20 mg/kg IV every 8-12 hours (not to exceed 2g per dose) targeting trough concentrations of 15-20 mg/L, with dose adjustments based on actual body weight and measured trough levels rather than creatinine clearance formulas alone. 1, 2

Initial Dosing Strategy

Standard Dosing

• Administer 15-20 mg/kg IV every 8-12 hours based on actual body weight (including obese patients), with individual doses not exceeding 2g 1, 2
• For seriously ill patients with suspected MRSA meningitis, consider a loading dose of 25-30 mg/kg (actual body weight) to rapidly achieve therapeutic levels 1
• Extend infusion time to 1.5-2 hours when individual doses exceed 1g to minimize red man syndrome risk 1

Dosing Frequency Determination

• Most patients with normal renal function require dosing every 8-12 hours to maintain target troughs 1
• The specific interval (8h vs 12h) should be determined by measured trough levels and renal function, not by creatinine clearance calculations alone 1

Therapeutic Drug Monitoring

Target Trough Concentrations

• Target trough serum concentrations of 15-20 mg/L for meningitis to ensure adequate CNS penetration and achieve AUC/MIC ≥400 1, 2
• Obtain trough levels just before the fourth dose (at steady state, approximately 48-72 hours after initiation) 1
• Trough monitoring is the most accurate and practical method; peak concentration monitoring is not recommended 1

Ongoing Monitoring

• Monitor trough levels before every fourth dose in patients with unstable renal function or those receiving prolonged therapy 1
• Adjust subsequent doses based on measured trough concentrations rather than nomograms, as standard nomograms were not designed to achieve these higher target troughs 1

Renal Function Considerations

Dose Adjustment Approach

• Do not use standard creatinine clearance-based dose reduction formulas for meningitis, as these will result in subtherapeutic CSF levels 1
• Instead, dose based on actual body weight initially, then adjust based on measured trough concentrations 1
• For patients with renal dysfunction, extend the dosing interval (e.g., every 24-48 hours) rather than reducing individual doses, to maintain adequate peak concentrations for CSF penetration 1
• Verify achievement of target trough concentrations (15-20 mg/L) through therapeutic drug monitoring regardless of renal function 1, 2

Critical Pitfall

The major pitfall is using standard vancomycin dosing protocols designed for non-CNS infections, which target lower trough levels (10-15 mg/L) and may result in treatment failure for meningitis 1. Even with dexamethasone co-administration, adequate CSF vancomycin levels (mean 7.2 mg/L) can be achieved with appropriate dosing (60 mg/kg/day continuous infusion or equivalent intermittent dosing) 3.

Alternative Agents for Severe Vancomycin Allergy

For Pneumococcal Meningitis

• Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours alone if the isolate is susceptible 1, 2
• If dual resistance to penicillin and cephalosporins is present, add rifampin 600 mg PO/IV twice daily to the cephalosporin 1, 2

For MRSA Meningitis

• Linezolid 600 mg PO/IV every 12 hours is the preferred alternative, as it achieves excellent CSF penetration 1, 2
• Alternative: TMP-SMX 5 mg/kg/dose IV every 8-12 hours 1
• Daptomycin is NOT recommended for meningitis due to poor CSF penetration and inactivation by pulmonary surfactant 1

MIC-Based Decision Making

When to Consider Alternatives

• If vancomycin MIC ≥2 mg/L, alternative therapy should be used, as target AUC/MIC ≥400 is not achievable with conventional dosing in patients with normal renal function 1
• For isolates with MIC ≤1 mg/L, trough concentrations of 15-20 mg/L should achieve adequate AUC/MIC ratios 1

Duration of Therapy

• 10-14 days for pneumococcal meningitis, with extension to 14 days for penicillin or cephalosporin-resistant strains 2
• 4-6 weeks for MRSA septic thrombosis of cavernous or dural venous sinus 1
• At least 10-14 days for post-neurosurgical meningitis with good clinical response 2

Nephrotoxicity Monitoring

• Monitor serum creatinine regularly during therapy 1
• Vancomycin-induced nephrotoxicity is defined as ≥2-3 consecutive increases in serum creatinine (≥0.5 mg/dL or ≥50% increase from baseline) after several days of therapy in the absence of alternative explanations 1, 2
• Risk is higher with trough concentrations >20 mg/L and concurrent nephrotoxic agents 1