Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis.
ABSTRACT The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels.
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ABSTRACT: Eight rifampin-resistant streptococci of the mitis group were identified at the species level by using a concatenated 16S rRNA gene-sodA-rpoB-hlpA sequence. Characterization of their rpoB alleles showed single amino acid changes involved in rifampin resistance. Comparison of RpoB sequences from pneumococcal recombinant isolates, viridans isolates, and type strains revealed a species-specific amino acid signature, which allowed it to be ascertained that recombinant RpoBs were originated in genetic interchanges with Streptococcus mitis and Streptococcus oralis.Antimicrobial Agents and Chemotherapy 11/2010; 55(1):368-72. · 4.57 Impact Factor
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ABSTRACT: To study mechanisms underlying generalized effects of 3β hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exposed to trilostane at two dosages for 24, 48, or 96 h and their gonadal RNA samples profiled with Agilent zebrafish microarrays. Trilostane had substantial impact on the transcriptional dynamics of zebrafish, as reflected by a number of differentially expressed genes (DEGs) including transcription factors (TFs), altered TF networks, signaling pathways, and Gene Ontology (GO) biological processes. Changes in gene expression between a treatment and its control were mostly moderate, ranging from 1.3 to 2.0 fold. Expression of genes coding for HSD3B and many of its transcriptional regulators remained unchanged, suggesting transcriptional up-regulation is not a primary compensatory mechanism for HSD3B enzyme inhibition. While some trilostane-responsive TFs appear to share cellular functions linked to endocrine disruption, there are also many other DEGs not directly linked to steroidogenesis. Of the 65 significant TF networks, little similarity, and therefore little cross-talk, existed between them and the hypothalamic-pituitary-gonadal (HPG) axis. The most enriched GO biological processes are regulations of transcription, phosphorylation, and protein kinase activity. Most of the impacted TFs and TF networks are involved in cellular proliferation, differentiation, migration, and apoptosis. While these functions are fairly broad, their underlying TF networks may be useful to development of generalized toxicological screening methods. These findings suggest that trilostane-induced effects on fish endocrine functions are not confined to the HPG-axis alone. Its impact on corticosteroid synthesis could also have contributed to some system wide transcriptional changes in zebrafish observed in this study.Ecotoxicology and Environmental Safety 05/2011; 74(6):1461-70. · 2.20 Impact Factor
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ABSTRACT: 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.Current Infectious Disease Reports 07/2010; 12(4):274-81.