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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESteroids have an important place in the treatment of bacterial meningitis.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EBacterial Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Diseases\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESteroids have an important place in the treatment of bacterial meningitis (BM), according to W. Michael Scheld, MD, University of Virginia, Charlottesville, Virginia, USA. Dr. Scheld was unable to attend this year\u0027s ICAAC, but graciously agreed to share highlights from that talk for the benefit of \u003Cem\u003EMD Conference Express\u003C\/em\u003E readers.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe rationale for employing anti-inflammatory medication in the treatment of BM is based upon the observation that hyperactive central nervous system (CNS) immune responses underlie brain swelling and neuronal loss and likely contribute to morbidity and mortality. In animals, steroids have been shown to reduce CNS inflammation, intracranial pressure, and neuronal loss. In addition, new investigational anti-inflammatory agents, such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (rTRAIL), significantly decrease cerebrospinal fluid leukocytes and apoptosis in mouse models of pneumococcal meningitis and significantly improve survival (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Hoffmann O et al. \u003Cem\u003EJ Clin Invest\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/28.1\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effects of Treatment with rTRAIL in Meningitis Induced By Live pneumococci in Mice.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-221024947\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Effects of Treatment with rTRAIL in Meningitis Induced By Live \u0026amp;lt;em\u0026amp;gt;pneumococci\u0026amp;lt;\/em\u0026amp;gt; in Mice.\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/28.1\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/28.1\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/11\/12\/28.1\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12463\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EEffects of Treatment with rTRAIL in Meningitis Induced By Live \u003Cem\u003Epneumococci\u003C\/em\u003E in Mice.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003E(A) At 24 hours after infection, CSF bacterial load in untreated and rTRAIL-treated wild-type mice did not differ. (B) CSF leukocyte concentration was significantly lower in rTRAIL-treated mice than in controls. **p\u0026lt;0.01, Student\u0027s t-test. (C) Mortality was higher in untreated versus rTRAIL-treated mice. **p\u0026lt;0.01, log rank test. (D) Apoptosis was reduced by treatment with rTRAIL. **p\u0026lt;0.01, Student\u0027s t-test.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EAfter review of the clinical literature over the past decade, Dr. Scheld believes that intravenous dexamethasone for the first 2 to 4 days in the treatment of community-acquired BM is indicatedin all ages in developed nations. De Gans et al. demonstrated an overall reduced risk for unfavorable outcomes and mortality in adults (RR=0.59; 95% CI, 0.37 to 0.94; p=0.03; and RR=0.48; 95% CI, 0.24 to 0.96; p=0.04, respectively) with dexamethasone [\u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2002]. Data from the Netherlands reveal that national implementation of adjunctive dexamethasone in patients with \u003Cem\u003ES. pneumoniae\u003C\/em\u003E BM has significantly reduced unfavorable outcomes, hearing loss, and mortality [Brouwer MC et al. \u003Cem\u003ENeurology\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIn contrast, steroids are not recommended where resources are limited and in populations with high HIV-positivity rates. A Vietnamese study showed a benefit to dexamethasone use only among patients with a proven microbiological diagnosis of BM but not among those with a probable diagnosis [Nguyen TH et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2007]. A study in Malawi among patients with high rates of HIV infection showed no benefit to using steroids in the treatment of BM [Scarborough M et al. \u003Cem\u003ENew Engl J Med\u003C\/em\u003E 2007]. Further, a 2010 meta-analysis that examined the issue showed that benefits of reduced hearing loss and neurologic sequelae, but not overall mortality among patients with BM who were treated with adjunctive steroids were observed in developed nations only [Brouwer MC et al. \u003Cem\u003ECochrane Rev\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EOther potential strategies for improving BM outcomes include selection of highly bactericidal, non lytic antibacterials such as rifampin, which has been shown to reduce \u03b2-lactam-induced cytotoxicity in animals [Spreer A et al. \u003Cem\u003ECrit Care Med\u003C\/em\u003E 2009], and daptomycin plus ceftriaxone, which has been associated with reduced neuronal injury and hearing loss [Grandgirad et al. ECCMID 2009]. In addition, prompt initiation of antibacterial therapy has been shown to reduce mortality [Proulx N et al. \u003Cem\u003EQ J Med\u003C\/em\u003E 2005; Auburtin M et al. \u003Cem\u003ECrit Care Med\u003C\/em\u003E 2006] and remains a central tenant of proper treatment.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/12\/28.1.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmxm1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmxm1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}