Timing of dexamethasone (DXM) therapy in experimental pneumococcal meningitis

I. Lutsar, I. R. Frdedland, L. Wubbel, A. Ahmed, M. Trujillo, H. Jafri, C. C. McCoig, G. H. McCracken

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Aim: to determine whether the timing of DXM administration in relation to antibiotic therapy influences inflammation and bactericidal activity in experimental pncumococcal meningitis. Methods and Results: Meningitis was induced in rabbits by intracisternal inoculation of pneumococcal cell wall components (equivalent to 108 bacteria) or a penicillin-susceptible pneumococcal strain (104-10S CFU). The latter group was trealed with ampicillin (amp) 75 mg/kg/q12h. DXM (1 mg/kg) was given 30 min before (DB) or 1 hour after (DA) the amp dose or cell wall inoculation. Untreated infected animals and animals treated with ceftriaxone (CRO) alone were used as a controls. Bacterial, WBC, TNF and lactate conc-s were measured in serial CSF samples. In cell wall induced meningitis DB, but not DA, significantly reduced WBC and lactate conc-s in CSF (p=0.02). TNF was inhibited by both DB and DA. In animals infected with live organisms and treated with amp, CSF lactate conc-s were reduced by 23% and 30% by DB and DA, resp. compared with those in animals not receiving DXM (p < 0.05). CSF conc-s of WBC and TNF were not influenced by DXM therapy. CRO therapy resulted in a greater bacterial killing rate compared with amp therapy (0.69 ± 0.16 vs 0.45 ± 0.17 CFU/ml/h for amp + DB and 0.38 ± 0.13 for DA; p< 0.02). Unlike amp therapy, CRO was not associated with increased CSF lactate conc-s. Conclusions: DXM modulated the inflammatory response in both cell-wall- and bacterial induced meningitis but early administration was important only in cell wall induced inflammation. CRO therapy was more rapidly bactericidal but did not result in increased inflammation compared with amp (with or without DXM) in this model of PM.

Original languageEnglish (US)
Number of pages1
JournalClinical Infectious Diseases
Issue number2
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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