Role of Meropenem in Pyogenic Meningitis
Meropenem is recommended as an effective alternative to third-generation cephalosporins for the treatment of bacterial meningitis, with particular value in treating meningitis caused by gram-negative bacilli that produce extended-spectrum β-lactamases or hyperproduce lactamases. 1
Primary Indications for Meropenem in Meningitis
Meropenem has been shown to have clinical and microbiologic outcomes similar to those of cefotaxime or ceftriaxone in bacterial meningitis and can be recommended as an alternative to these agents 1
Particularly valuable for treating meningitis caused by gram-negative bacilli that produce extended-spectrum β-lactamases or those that hyperproduce lactamases (i.e., Enterobacter species, Citrobacter species, or Serratia marcescens) 1, 2
Specifically indicated when there is high suspicion of ESBL-producing organisms, with a recommended dose of 2g IV every 8 hours 1
FDA-approved for bacterial meningitis in pediatric patients 3 months of age and older at a dose of 40 mg/kg every 8 hours (maximum 2 grams every 8 hours) 3
Advantages Over Other Carbapenems
Meropenem has a broad range of in vitro activity and less seizure proclivity than imipenem, making it safer for CNS infections 1
Unlike imipenem, which showed a 33% seizure rate in one study of children with bacterial meningitis, meropenem has a low propensity for inducing seizures 1, 4
Can be administered as an intravenous bolus or infusion, providing flexibility in administration 4
Clinical Evidence and Efficacy
Clinical studies have demonstrated that meropenem has similar efficacy to cefotaxime in both pediatric and adult patients with bacterial meningitis 4, 5
In a randomized comparison study, clinical cure was observed in 100% of evaluable patients treated with meropenem compared to 77% in cephalosporin-treated patients 5
A quality registry study (2008-2016) showed comparable 30-day mortality rates between meropenem (3.6%) and cefotaxime plus ampicillin (3.2%) in adult bacterial meningitis 6
Limitations and Considerations
For pneumococcal meningitis caused by highly penicillin- and cephalosporin-resistant strains, meropenem may not be a useful alternative agent 1
In a study of 20 cefotaxime-resistant S. pneumoniae isolates, 4 were intermediate and 13 were resistant to meropenem 1
To preserve carbapenem effectiveness, guidelines recommend third-generation cephalosporins as empirical treatment for the majority of patients with bacterial meningitis 6
Dosing Recommendations
For adults with bacterial meningitis: 2g IV every 8 hours 1
For pediatric patients (≥3 months): 40 mg/kg every 8 hours (maximum 2 grams every 8 hours) 3
Treatment duration should be 21 days for Enterobacteriaceae infections 1
Dosage should be reduced in patients with renal impairment according to creatinine clearance 3
Combination Therapy Considerations
The addition of rifampin to meropenem did not improve activity in an experimental model of pneumococcal meningitis 7
For pneumococcal meningitis caused by highly resistant strains, some authorities recommend combination therapy with a third-generation cephalosporin plus vancomycin 1
Current Position in Treatment Guidelines
Meropenem is positioned as an alternative to third-generation cephalosporins rather than first-line therapy for most cases of bacterial meningitis 1, 6
It should be reserved for specific situations such as gram-negative meningitis with suspected resistance to standard therapy, particularly ESBL-producing organisms 1, 2
Particularly valuable in nosocomial meningitis by multiresistant gram-negative bacilli such as Klebsiella-Serratia-Enterobacter and Acinetobacter species 8