A study was conducted to determine the utility of adjunctive therapy in bacterial meningitis. Patients with acute bacterial meningitis whose cerebrospinal fluid (CSF) analysis showed gram-positive diplococci were divided into 2 groups. The first (control) group was given systemic antibiotics only, and the second (experimental) group was given dexamethasone followed by systemic antibiotics. Compared to the control group, patients in the experimental group developed fewer neurologic sequelae and had a lower risk of death. The experimental patients most likely benefited from the use of this drug due to which of the following?

Question

A study was conducted to determine the utility of adjunctive therapy in bacterial meningitis.  Patients with acute bacterial meningitis whose cerebrospinal fluid (CSF) analysis showed gram-positive diplococci were divided into 2 groups.  The first (control) group was given systemic antibiotics only, and the second (experimental) group was given dexamethasone followed by systemic antibiotics.  Compared to the control group, patients in the experimental group developed fewer neurologic sequelae and had a lower risk of death.  The experimental patients most likely benefited from the use of this drug due to which of the following?

Quizplus · Accepted Answer

Acute bacterial meningitis is characterized by a massive inflammatory response in the central nervous system. The inflammation is driven by bacterial subcapsular components, particularly macromolecules of the bacterial cell wall such as teichoic acid and peptidoglycan. These components trigger the release of inflammatory cytokines (eg, tumor necrosis factor-alpha, interferon-gamma, interleukin 12), leading to loosening of the tight junctions of the blood-brain barrier, vasogenic edema, elevation of intracranial pressure, and recruitment of leukocytes. Streptococcus pneumoniae, a gram-positive diplococcus, is the leading cause of acute bacterial meningitis in adults. Initial antibiotic therapy against S pneumoniae lyses the bacteria and releases cell wall components that increase cerebrospinal fluid (CSF) inflammatory cytokines. Studies have shown that pretreatment with dexamethasone reduces the levels of inflammatory cytokines in the CSF and limits risk of inflammation-induced morbidity (eg, seizures, focal neurologic deficits) and death. Other forms of bacterial meningitis, such as those due to Neisseria meningitidis and Haemophilus influenzae, do not benefit from glucocorticoid pretreatment, possibly because these gram-negative organisms have thinner cell walls (less peptidoglycan and no teichoic acid), resulting in less inflammatory cytokine release. (Choice A) Therapeutic hypothermia (32-34 C [89.6-93.2 F]) can be used after hypoxic/ischemic brain injury due to cardiac arrest. It reduces cerebral metabolic activity and limits metabolic strain within damaged neurologic tissue. This has been shown to improve neurologic recovery and long-term outcomes. (Choice C) The inflammatory response to bacterial components in the CSF loosens the tight junctions of the blood-brain barrier, which aids antibiotic penetration into the central nervous system. Dexamethasone reduces the inflammatory response and would be expected to decrease permeability of the blood-brain barrier. (Choice D) Glucocorticoids promote the release of granulocytes from the bone marrow and the movement of neutrophils off the endothelial wall into the systemic circulation. This often leads to an increase in the circulating white blood cell count with delayed migration into infected tissues. (Choice E) Glucocorticoids can cause a dose-dependent increase in fasting serum glucose levels due to stimulation of hepatic gluconeogenesis and inhibition of glucose uptake in adipose tissue. Educational objective: Pneumococcal meningitis is associated with massive cerebrospinal fluid inflammatory cytokine release in response to bacterial cell wall components. Treatment with dexamethasone prior to antibiotic therapy has been shown to reduce inflammation and decrease the risk of adverse outcomes (eg, seizures, focal neurologic deficits) and death. Other forms of bacterial meningitis do not seem to benefit from glucocorticoid treatment.

A Study Was Conducted to Determine the Utility of Adjunctive