Treatment of Drug-resistant Pneumococcal Meningitis.

The approach to therapy in patients with pneumococcal meningitis has changed considerably over the past 20 years. Given the emergence of pneumococcal strains that are intermediately susceptible or highly resistant to penicillin, penicillin is not recommended as empiric therapy for presumed pneumococcal meningitis; the combination of vancomycin and a third-generation cephalosporin (either cefotaxime or ceftriaxone) should be used, pending isolation of the organism and in vitro susceptibility testing. For patients with pneumococcal meningitis caused by highly penicillin- or cephalosporin-resistant strains, the addition of rifampin can be considered if the organism is susceptible in vitro, the expected clinical or bacteriologic response is delayed, or the pneumococcal isolate has a cefotaxime or ceftriaxone minimal inhibitory concentration greater than 4 μg/mL. Meropenem is not a good option for monotherapy of highly penicillin- or cephalosporin-resistant strains, but use of a fluoroquinolone with in vitro activity against Streptococcus pneumoniae (specifically moxifloxacin) is an option in patients failing standard therapy; if used, however, it should be combined with a third-generation cephalosporin or vancomycin. Newer glycopeptides, daptomycin, and linezolid require further study to determine their efficacy in patients with pneumococcal meningitis.