MD Conference Express ICAAC 2011 - (Page 28)
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The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Written by Noelle Lake, MD
Steroids 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’s ICAAC, but graciously agreed to share highlights from that talk for the benefit of MD Conference Express readers. The 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 factorrelated apoptosis-inducing ligand (rTRAIL), significantly decrease cerebrospinal fluid leukocytes and apoptosis in mouse models of pneumococcal meningitis and significantly improve survival (Figure 1) [Hoffmann O et al. J Clin Invest 2007]. Figure 1. Effects of Treatment with rTRAIL in Meningitis Induced By Live pneumococci in Mice.
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CSF Bacteria (CFU/ml)
After 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 communityacquired 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 [New Engl J Med 2002]. Data from the Netherlands reveal that national implementation of adjunctive dexamethasone in patients with S. pneumoniae BM has significantly reduced unfavorable outcomes, hearing loss, and mortality [Brouwer MC et al. Neurology 2010]. In contrast, steroids are not recommended where resources are limited and in populations with high HIVpositivity 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. New Engl J Med 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. New Engl J Med 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. Cochrane Rev 2010]. Other potential strategies for improving BM outcomes include selection of highly bactericidal, non lytic antibacterials such as rifampin, which has been shown to reduce β-lactam-induced cytotoxicity in animals [Spreer A et al. Crit Care Med 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. Q J Med 2005; Auburtin M et al. Crit Care Med 2006] and remains a central tenant of proper treatment.
A.
CSF Leukocytes (1/µl)
12000 10000 8000 6000 4000 2000 0
B.
p<0.01, Student’s T-Test
108
107
106
0
rTRAIL (µg)
1
0
rTRAIL (µg)
1
100
Survival (%)
C.
Untreated
rTRAIL (µg)
200
TUNEL + Cells/mm2 at 24 hours
D.
p<0.01, Student’s T-Test
80 60 40 20 0 p<0.01 log rank test
150 100 50 0
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten
0 rTRAIL (µg) 1
0
4
8
12 16 Hours
20
24
Written by Noelle Lake, MD
(A) At 24 hours after infection, CSF bacterial load in untreated and rTRAILtreated wild-type mice did not differ. (B) CSF leukocyte concentration was significantly lower in rTRAIL-treated mice than in controls. **p<0.01, Student’s t-test. (C) Mortality was higher in untreated versus rTRAILtreated mice. **p<0.01, log rank test. (D) Apoptosis was reduced by treatment with rTRAIL. **p<0.01, Student’s t-test.
While infectious diseases are no longer a major cause of mortality in developed countries, new viral infections continue to emerge due to our globalizing and changing
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November 2011
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Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011
MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten
MD Conference Express ICAAC 2011
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