In children with bacterial meningitis, does the addition of dexamethasone to an antibiotic treatment regimen result in a better clinical outcome than the antibiotic regimen alone?

Fox, James Lr

doi:10.1093/pch/11.1.33

Cited by 5 publications

(5 citation statements)

References 12 publications

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“…While our study and that of Cucullo et al demonstrated that DEX increased the TEER, these observations further illustrate the dissociation between permeability to small ions and permeability to AMB (5). Concerns have been raised about decreasing the BBB permeability to antimicrobial agents by administering corticosteroids in patients with CNS infections (8). Reduced permeability to AMB was not observed when the effect of DEX was studied in this in vitro model.…”

Section: Discussionsupporting

confidence: 72%

Effects of Immunomodulatory and Organism-Associated Molecules on the Permeability of anIn VitroBlood-Brain Barrier Model to Amphotericin B and Fluconazole

Pyrgos

Mickiene

Sein

et al. 2010

Antimicrob Agents Chemother

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Amphotericin B (AMB) is used to treat fungal infections of the central nervous system (CNS). However, AMB shows poor penetration into the CNS and little is known about the factors affecting its permeation through the blood-brain barrier (BBB). Therefore, we studied immunomodulatory and organism-associated molecules affecting the permeability of an in vitro BBB model to AMB. We examined the effects of interleukin-1 beta (IL-1␤), tumor necrosis factor alpha (TNF-␣), lipopolysaccharide (LPS), lipoteichoic acid (LTA), zymosan (ZYM), dexamethasone (DEX), cyclosporine, and tacrolimus on transendothelial electrical resistance (TEER); endothelial tight junctions; filamentous actin; and permeability to deoxycholate AMB (DAMB), liposomal AMB (LAMB), and fluconazole. Proinflammatory cytokines and organism-associated molecules significantly decreased the mean TEER by 40.7 to 100% (P < 0.004). DEX increased the mean TEER by 18.2 to 26.4% (P < 0.04). TNF-␣ and LPS increased the permeability to AMB by 8.2 to 14.5% compared to that for the controls (1.1 to 2.4%) (P < 0.04). None of the other molecules affected the model's permeability to AMB. By comparison, the BBB model's permeability to fluconazole was >78% under all conditions studied, without significant differences between the controls and the experimental groups. LPS and TNF-␣ decreased tightjunction protein zona occludens 1 (ZO-1) between endothelial cells. In conclusion, IL-1␤, ZYM, and LTA increased the permeability of the BBB to small ions but not to AMB, whereas TNF-␣ and LPS, which disrupted the endothelial layer integrity, increased the permeability to AMB.Amphotericin B (AMB) and fluconazole are important antifungal agents used to treat invasive fungal infections of the central nervous system (CNS). AMB is commonly used in the treatment of cryptococcal meningitis, rhinocerebral zygomycosis, hematogenous candida meningoencephalitis, and other invasive fungal infections of the CNS (7,16,18). AMB was effective for the treatment of experimental hematogenous candida meningoencephalitis in rabbits, but it demonstrated poor penetration into the cerebrospinal fluid (CSF) and brain tissue (10). While the penetration of AMB into CSF and brain parenchyma is poor, it remains an effective agent against CNS mycoses (20). By comparison, fluconazole displays a relatively high level of penetration into the CNS (2). Variables which might influence the permeability of the blood-brain barrier (BBB) to AMB, such as cytokines, organism-associated molecules, and immunosuppressants, have not been fully evaluated. We therefore studied the effects of several such factors on an in vitro mammalian BBB model. We examined the effects of those variables on interendothelial tight junctions; the structure of filamentous actin; and the permeability of the in vitro BBB model to AMB, fluconazole, and small ions. MATERIALS AND METHODS Cells. Bovine brain microvascular endothelial cells (BBECs; Cell ApplicationsInc., San Diego, CA) were grown in 75-cm 2 collagen-coated tissue culture flasks with BBEC ...

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Section: Discussionsupporting

confidence: 72%

Effects of Immunomodulatory and Organism-Associated Molecules on the Permeability of anIn VitroBlood-Brain Barrier Model to Amphotericin B and Fluconazole

Pyrgos

Mickiene

Sein

et al. 2010

Antimicrob Agents Chemother

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“…In few clinical trials improved neurological sequelae was observed in severe meningitis cases, particularly those suffering from Streptococcus pneumoniae and Haemophilus influenzae patients. 24,25 Here, 46% of patients who were suffering from severe meningitis, received the dexamethasone whereas 54% who were suffering from the moderate grade of meningitis did not receivedexamethasone. The group who received dexamethasone have a mean duration of hospitalization 13.4 days and that of non-dexamethasone receiving group of 7.6 days.…”

Section: Discussionmentioning

confidence: 96%

An observational study for evaluation of antibiotic utilization and growing resistance against antibiotics in pediatric patients suffering from meningitis in a tertiary care hospital

Bhattacharyya

Ghosh

2023

Asian J Med Sci

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Background: Meningitis, inflammation of the meninges with systemic septicemia, from the bacterial, viral, or fungal origin, is a fatal disease in all age groups, particularly infants and children. The present study was done to evaluate the usage of antibiotics in pediatric patients with meningitis in a tertiary care hospital. Aims and Objectives: The study was conducted to evaluate the prescription pattern of antibiotics for pediatric patients suffering from meningitis. The efficacy of antibiotics, combination of antibiotics, and the resistance developed against them were reevaluated. Materials and Methods: An observational, noninterventional study with 34 pediatric patients (The mean age of the patients were 6.17 year. ±4.84 SD) admitted in Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar from September 2012 to February 2014 were evaluated. Data were collected after the approval of the research protocol by the Institutional Ethics committee, KIMS from case sheets of patients from the ward as well as the Medical Record and Data section. Comparative statistical analysis was done by using student’s t-test in respect of data measured on a continuous scale. All differences with P<0.05 were labeled as statistically significant. Results: Ceftriaxone±ß lactamase inhibitor (βLI) (77.4%), and Cefoperazone±βLI (12.9%) were the most frequently used cephalosporin. In 55.8% of patients, three or more antibiotics in combination were given. Two drugs regimen like β lacatam+aminoglycoside in 23.5% of patients and β lactam+anti-Methicillin-resistant Staphylococcus aureus (MRSA) in 20.6% were given. Emerging resistance pattern against both Gram-positive cocci and Gram-negative bacilli to penicillins, cephalosporins, and aminoglycosides which are the primary first-line drugs has been observed. Conclusion: Very severe meningitis patients were treated with multiple antibiotics including anti-MRSA agents. High resistance (≥60%) was observed against β lactams.

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“…An evidence based summary was done in 2006 by James LR that included databases from the PubMED, the Cochrane library, and the EMBASE, where the results of this review showed the beneficial effects of adjuvant dexamethasone when given just before or with the start of antibiotics in children with meningitis due to Hib and non-Hib pathogens. In addition, the review also showed the effects of dexamethasone in the reduction of severe hearing loss that was also seen in both Hib and other bacterial meningitis [10,23] (grade A recommendation). [24].…”

Section: Discussionmentioning

confidence: 99%

“…[11] To our knowledge there is no clear consensus of the duration of dexamethasone to be administered; however, most studies have used a regimen ranging from 0.4mg/kg to 0.6 mg/kg administered every 6 hours and continued for four days. [10].…”

Section: Discussionmentioning

confidence: 99%

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Profound Sensorineural Hearing Loss Following Adjuvant Steroid Delay in Pediatric Bacterial Meningitis

Topalian¹,

Mansour²,

Wehbe³

et al. 2022

AJP

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Streptococcus pneumonia is a gram positive, polysaccharide-encapsulated diplococcus associated with various pulmonary and extra-pulmonary clinical presentations including invasive diseases such as acute meningitis. It can be associated with high rates of morbidity and mortality in both the pediatric and the adult populations. The introduction of the pneumococcal conjugate vaccine which expanded to cover 13 strains allowed remarkable protection against these invasive infections. In addition, the use of adjuvant corticosteroid therapy in the last few years; in particular dexamethasone, for the management of acute bacterial meningitis reduced the incidence of severe hearing loss in both Hib and other bacterial meningitis. The IDS guidelines recommend administering the first dose of steroids just before or with the start of antibiotics due to its decreased effectiveness with the late presentations of meningitis. We present the case of a 14-year-old female adolescent refugee, with incomplete vaccination status prior to relocating to Lebanon presenting with pneumococcal meningitis. Her hospitalization was complicated by bilateral profound sensorineural hearing loss (SNHL) following a delay in steroid administration. The aim of this article is to highlight the role of vaccines in decreasing morbidity of vaccinepreventable illnesses, and the importance of early administration of steroids as adjuvant to therapy for prevention of neurologic sequeleae.

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In children with bacterial meningitis, does the addition of dexamethasone to an antibiotic treatment regimen result in a better clinical outcome than the antibiotic regimen alone?

Cited by 5 publications

References 12 publications

Effects of Immunomodulatory and Organism-Associated Molecules on the Permeability of anIn VitroBlood-Brain Barrier Model to Amphotericin B and Fluconazole

Effects of Immunomodulatory and Organism-Associated Molecules on the Permeability of anIn VitroBlood-Brain Barrier Model to Amphotericin B and Fluconazole

An observational study for evaluation of antibiotic utilization and growing resistance against antibiotics in pediatric patients suffering from meningitis in a tertiary care hospital

Profound Sensorineural Hearing Loss Following Adjuvant Steroid Delay in Pediatric Bacterial Meningitis

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