What is the recommended treatment for a patient with meropenem-resistant bacterial meningitis, considering factors such as age, weight, and impaired renal function?

Treatment of Meropenem-Resistant Bacterial Meningitis

For meropenem-resistant bacterial meningitis, use combination therapy with a third-generation cephalosporin (ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours) plus vancomycin 15-20 mg/kg IV every 12 hours plus rifampicin 600 mg IV/orally every 12 hours for 14 days. 1

Understanding Meropenem Resistance in Meningitis

The critical issue is that meropenem resistance typically indicates highly resistant pneumococcal strains that are also resistant to penicillins and cephalosporins. 1 In a study of 20 cefotaxime-resistant S. pneumoniae isolates, 4 were intermediate and 13 were resistant to meropenem, demonstrating that meropenem is not a useful alternative for highly resistant pneumococcal strains. 1

Primary Treatment Regimen

Triple Combination Therapy (First-Line)

For pneumococcal meningitis that is both penicillin and cephalosporin resistant (which typically correlates with meropenem resistance):

• Ceftriaxone 2g IV every 12 hours OR Cefotaxime 2g IV every 6 hours 1
• PLUS Vancomycin 15-20 mg/kg IV every 12 hours (maintain serum trough 15-20 mg/mL) 1
• PLUS Rifampicin 600 mg IV/orally every 12 hours (only if organism is susceptible and there is delayed clinical response) 1

Duration of Therapy

• 14 days for penicillin or cephalosporin-resistant pneumococcal meningitis 1
• Continue treatment for full 14 days regardless of clinical improvement given the resistance pattern 1

Dosing Adjustments for Special Populations

Renal Impairment

Critical adjustment required to prevent neurotoxicity:

• CrCl 26-50 mL/min: Reduce dose, extend interval to every 12 hours 2
• CrCl 10-25 mL/min: Give one-half recommended dose every 12 hours 2
• CrCl <10 mL/min: Give one-half recommended dose every 24 hours 2

Vancomycin dosing must also be adjusted based on renal function to maintain therapeutic trough levels of 15-20 mg/mL. 1

Pediatric Patients (≥3 months)

• Ceftriaxone 2g IV every 12 hours OR Cefotaxime 2g IV every 6 hours 1
• PLUS Vancomycin 15-20 mg/kg IV every 12 hours 1
• PLUS Rifampicin 600 mg every 12 hours 1

Elderly Patients (≥60 years)

• Same dosing as adults, but mandatory renal function monitoring as elderly patients are more likely to have decreased creatinine clearance 2
• Consider adding Amoxicillin 2g IV every 4 hours for Listeria coverage in this age group 1

Alternative Considerations for Gram-Negative Resistance

If the meropenem-resistant organism is a gram-negative bacillus (Enterobacteriaceae, Pseudomonas, Acinetobacter):

For ESBL-Producing Organisms

• Meropenem 2g IV every 8 hours remains appropriate despite general "resistance" if susceptibility testing shows activity 1, 3, 4
• Infuse over 1.5-2 hours when doses exceed 1g to reduce seizure risk 5

For Carbapenem-Resistant Gram-Negatives

• Fluoroquinolones (ciprofloxacin or moxifloxacin) for multidrug-resistant gram-negative bacilli when standard therapy has failed 1
• Must be combined with vancomycin or a third-generation cephalosporin 6
• Consider intrathecal therapy in consultation with infectious disease specialists 1

Critical Monitoring Parameters

Clinical Response Assessment

• Neurological examination and Glasgow Coma Score at baseline and daily 7
• CSF sterilization should occur by 24-48 hours; if not, reassess therapy 8
• Vancomycin serum trough levels: maintain 15-20 mg/mL 1

Common Pitfalls to Avoid

1. Do not use meropenem monotherapy for highly resistant pneumococcal meningitis - it has demonstrated regrowth in CSF at 24 hours in experimental models 8

2. Do not add rifampicin empirically - only add if organism is proven susceptible and there is delayed clinical or bacteriologic response 1

3. Do not forget renal dose adjustments - failure to adjust for creatinine clearance ≤50 mL/min increases neurotoxicity risk significantly 2

4. Do not rely on in vitro susceptibility alone for meropenem - clinical outcomes may be poor even with apparent susceptibility in highly resistant strains 1, 6

When to Consider Intrathecal Therapy

Intrathecal vancomycin may be considered in patients not responding to parenteral administration, particularly in cases of highly resistant organisms with poor CSF penetration. 1 This requires infectious disease consultation and neurosurgical expertise for administration.

Organism-Specific Considerations

If Neisseria meningitidis is Identified

• Meropenem resistance is extremely rare in meningococcus 1
• Standard ceftriaxone or cefotaxime alone is sufficient 1, 5
• Treatment duration: 5 days if clinically recovered 1

If Streptococcus pneumoniae is Identified

• Assume multi-drug resistance if meropenem-resistant 1
• Use triple therapy as outlined above 1
• Treatment duration: 14 days 1