The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 ,g/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

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A monoclonal antibody (MAb) to Moraxella catarrhalis O35E bound to a surface-exposed epitope of a proteinaceous antigen of this organism. The antigen, designated UspA, was present in every strain of the pathogen tested in a colony blot RIA. UspA had a molecular mass on SDS-PAGE that varied between 300 and 400 kDa, depending on the individual M. catarrhalis strain. Passive immunization of mice with the UspA-reactive Mab enhanced pulmonary clearance of M. catarrhalis. Use of this Mab to screen a M. catarrhalis genomic DNA library permitted identification of a recombinant bacteriophage expressing the M. catarrhalis UspA protein. The recombinant UspA protein was used in Western blot analysis with sera from patients with M. catarrhalis pneumonia. Convalescent-phase sera but not acute-phase sera from these patients contained antibodies to this M. catarrhalis surface protein, indicating that M. catarrhalis strains growing in vivo express this molecule.

Treatment of pneumococcal meningitis has become problematic because of the emergence of penicillin-and cephalosporin-resistant strains and because of the concern that dexamethasone therapy might reduce penetration of antibiotics into the cerebrospinal fluid (CSF). We addressed these issues with our rabbit meningitis model by studying two pneumococcal isolates that were resistant to penicillin and ceftriaxone and susceptible to vancomycin and rifampin. Ceftriaxone, vancomycin, and rifampin were given alone or in combination, with or without coadministration of dexamethasone. Treatment was started 12 to 14 h after intracisternal inoculation of i104 CFU of one of the organisms. Rifampin concentrations in serum and CSF were similar, regardless of whether dexamethasone was given, whereas those of ceftriaxone were somewhat lower at each time point in animals given dexamethasone. The penetration of vancomycin into CSF was consistently and substantially reduced with dexamethasone treatment, which resulted in a delay in CSF sterilization not observed in non-dexamethasone-treated animals. When rifampin was used with ceftriaxone for treatment of meningitis caused by the more resistant strain, bacteriologic cure occurred promptly, with or without dexamethasone therapy. In areas with high rates of occurrence of resistant pneumococcal strains, we believe initial empiric therapy of bacterial meningitis should include two antibiotics: ceftriaxone and either rifampin or vancomycin. When dexamethasone is used, the combination of ceftriaxone and rifampin is preferred for therapy.Dexamethasone has been shown to improve the long-term outcome in infants and children with bacterial meningitis, especially meningitis caused by Haemophilus influenzae type b (19,20,27,28). Its role in the management of Streptococcus pneumoniae meningitis is uncertain, although a retrospective study of 97 infants and children (18) and a prospective trial in 106 older patients (15) with pneumococcal meningitis suggested a satisfactory effect. With routine use of conjugate Haemophilus vaccines in many countries, meningitis caused by this organism has virtually disappeared (1,4,6,23,26,29), leaving the pneumococcus and meningococcus as the principal causes of meningitis in these areas.Attention has recently focused on management of pneumococcal meningitis because of the emergence of penicillin-and cephalosporin-resistant strains (7,8,10,11 (214) 648-2961. showed synergistic killing of resistant pneumococci in the rabbit meningitis model (12), and this regimen has been suggested for routine initial therapy of bacterial meningitis until results of culture and susceptibility studies are available.Because of concerns about the highly variable concentrations of vancomycin in cerebrospinal fluid (CSF) after parenteral administration (22,34) and about possible reduced penetration of vancomycin into CSF when dexamethasone is concomitantly given, the present study was undertaken. The impact of dexamethasone therapy on the decrease of clearance of resistant pneum...