Treatment. Because bacterial meningitis is a life-threatening illness, hospitalization and prompt initiation of antibiotics are required. Targeted antimicrobial therapy is based on presumptive pathogen identification by CSF Gram staining—for example:
• Gram-positive diplococci suggest pneumococcal infection (treat with vancomycin(Drug information on vancomycin) and ceftriaxone(Drug information on ceftriaxone) or cefotaxime(Drug information on cefotaxime)).
• Gram-negative diplococci suggest meningococcal infection (treat with ceftriaxone or cefotaxime).
• Small pleomorphic gram-negative coccobacilli suggest Haemophilus influenzae (treat with ceftriaxone or cefotaxime).
• Gram-positive rods and coccobacilli suggest listerial infection (treat with ampicillin(Drug information on ampicillin)).
If empiric antibiotic treatment is required, the IDSA recommends an antimicrobial regimen consisting of vancomycin, and ceftriaxone or cefotaxime; ampicillin is also added, depending on the age of the patient and on whether listerial infection is suspected.8 As CSF and blood cultures return, the antimicrobial coverage can be narrowed and made more specific against isolated organisms.
The role of dexamethasone(Drug information on dexamethasone) as an adjunctive treatment was evaluated in a Cochrane systematic review.9 The pathophysiological rationale for adjunctive corticosteroid use is based on experimental animal models of infection, which have shown that the inflammatory response during bacterial meningitis is a major factor contributing to morbidity and mortality. One large clinical trial, which used the following regimen, forms the basis for current guidelines on the appropriate dosing of dexamethasone in adults: dexamethasone should be given 15 to 20 minutes before or at the time of antibiotic administration—at a dose demonstrating efficacy—0.15 mg/kg every 6 hours for 4 days.10 The IDSA recommends that initiation of dexamethasone with antibiotics be reserved for adult patients with suspected or proven pneumococcal meningitis who have not already received antimicrobial therapy. This is based on trials that demonstrated limited benefit in meningitis caused by other meningeal pathogens; however, some argue that dexamethasone treatment should be initiated in all adult patients, since the cause of meningitis is not always ascertained or readily apparent at initial evaluation. These same trials did, however, suggest benefit with adjunctive dexamethasone treatment in patients with moderate to severe disease on the Glasgow Coma Scale.8
HERPES SIMPLEX VIRUS TYPE 1 ENCEPHALITIS
Overview. Herpes simplex virus type 1 (HSV-1) is the most common cause of sporadic fatal encephalitis throughout the world. In the United States, HSV-1 encephalitis accounts for about 10% to 20% of the annual viral encephalitis cases11,12 and is associated with significant morbidity and mortality.
Infection of the CNS by HSV-1 is believed to occur through 1 of 3 routes11:
• Primary HSV-1 of the oropharynx with subsequent infection of the CNS via the olfactory tract or trigeminal nerve.
• Viral reactivation or recurrent HSV-1 infection with spread into the CNS.
• Reactivation of latent HSV within the CNS (ie, in patients without primary or recurrent HSV-1 infection).
Clinical features. Patients may complain of headache and fever of rapid onset. In addition, patients may present with 1 or more focal neurological findings, such as13:
• Altered mentation or impaired
• Cranial nerve deficits.
HSV-1 is known to have affinity for the temporal lobe and limbic structures, and patients may demonstrate behavioral syndromes (eg, hypomania, Klüver-Bucy syndrome, varying levels of amnesia) that correspond with this phenomenon.13,14
Diagnostic studies. CSF analysis in patients with HSV-1 encephalitis typically shows a lymphocytic pleocytosis with an increased number of erythrocytes and an elevated protein level; however, results may be normal early in the disease course.15 Imaging studies (particularly MRI) of the brain may also prove useful in strengthening the clinical suspicion of HSV-1 encephalitis, particularly if temporal lobe abnormalities can be demonstrated. The characteristic temporal lobe lesions are usually unilateral and may have associated mass effect.
Despite the classic findings on CSF analysis and imaging studies, the gold standard for diagnosis of HSV-1 encephalitis is the detection of HSV DNA in the CSF by means of polymerase chain reaction (PCR).16,17 Treatment should not be delayed pending the results of PCR testing, however.
Treatment. Because of the high morbidity and mortality associated with HSV-1 encephalitis, hospitalization and prompt initiation of acyclovir are required. The duration of treatment is 14 to 21 days.13,18,19 Mortality in untreated patients may be as high as 70% and decreases only to 20% to 30% in those who receive appropriate treatment. Survivors may have significant behavioral and cognitive impairments despite treatment.13,18 Early and aggressive antiviral therapy with acyclovir may help prevent fatality and limit the severity of potential neurobehavioral and neuropsychiatric problems.