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Harrison’s Manual of Medicine



Acute Bacterial Meningitis
Brain Abscess
Subdural Empyema

The pathogens most frequently involved in bacterial meningitis in immunocompetent adults are Streptococcus pneumoniae (“pneumococcus”) and Neisseria meningitidis (“meningococcus”). Predisposing factors for pneumococcal meningitis include distant foci of infection (otitis, sinusitis, pneumonia, endocarditis), asplenia, sickle cell disease, hypogammaglobulinemia, multiple myeloma, alcoholism, cirrhosis, and recent head trauma with CSF leak. Pts with deficiency of terminal complement components, or properdin, are at increased risk of meningococcal infection, which may also occur in epidemics. Although vaccination has dramatically reduced the incidence of Haemophilus influenzae meningitis, this organism is still an important cause of meningitis in unvaccinated children (age 3 mos to 18 yrs) and in adults with predisposing risk factors (e.g., otitis, sinusitis, epiglottitis, pneumonia, alcoholism, diabetes, immunocompromise, asplenia). Pts with impaired cell-mediated immunity, neonates, the elderly, diabetics, and alcoholics are at increased risk of infection caused by Listeria monocytogenes and a variety of gram-negative organisms. Recent head trauma, neurosurgery, or ventricular shunts are risk factors for both gram-negative and staphylococcal infections.
Clinical Manifestations   Presentation is either as an acute fulminant illness that progresses over a few hours or as a subacute infection that progressively worsens over several days. 85% of adults have headache, fever, and meningismus (stiff neck). Additional signs can include altered mental status (75%), nausea and vomiting, cranial nerve palsies, seizures (40%), myalgias, sweating, and photophobia. Signs of meningismus include resistance to neck flexion, Kernig’s sign (patient in supine position, hip and knee flexed; pain induced by attempt to extend leg), and Brudzinski’s sign (passive flexion of neck results in spontaneous flexion of hip and knees). Meningismus and fever may be absent in neonates and the elderly. The rash of meningococcemia begins as a diffuse maculopapular rash resembling a viral exanthem but rapidly becomes petechial on trunk and lower extremities, mucous membranes and conjunctiva, and occasionally on palms and soles. Rash may also occur with other organisms.
Laboratory Findings   Lumbar puncture (LP) is critical to the diagnosis of bacterial meningitis (Table 184-1). Key CSF findings include a CSF leukocytosis with neutrophilic predominance, an elevated protein, hypoglycorrhachia (decreased glucose), and elevated opening pressure. Mononuclear cells may predominate as infection continues. CSF white counts >50,000/µL should suggest the possibility of intraventricular rupture of brain abscess. Gram stain reveals organisms in 75% of untreated pts, and cultures are positive in 70–80%. Latex agglutination test may be helpful, especially in partially treated meningitis. Blood cultures should always be obtained and are positive in 50% of pts. Petechial skin lesions should also be biopsied if the etiology is in doubt. In pts with focal neurologic findings or papilledema, LP may be deferred pending emergency CT or MRI; however, treatment must not be delayed in such cases but should be started empirically after obtaining blood cultures.

Table 184-1 Cerebrospinal Fluid Abnormalities in Bacterial Meningitis

Differential Diagnosis   Includes viral meningoencephalitis, especially herpes simplex virus encephalitis (distinctive neuroimaging and EEG features; Chap. 185); rickettsial diseases such as Rocky Mountain spotted fever (immunoflourescent staining of skin lesions); focal suppurative CNS infections including subdural empyema and brain abcess (see below); subarachnoid hemorrhage (diagnostic neuroimaging and CSF features; Chap. 35); and the demyelinating disease acute disseminated encephalomyelitis.

Recommendations for empirical therapy, shown in Table 184-2, are based on the pt’s age, immunologic status, presence or absence of recent head trauma or neurosurgery, and CSF Gram’s stain results. Therapy is then modified based on results of CSF culture (Table 184-3). In general, the treatment course is 7 days for meningococcus, 14 days for pneumococcus, 21 days for gram- negative meningitis, and at least 21 days for L. monocytogenes. Children (³2 mos) should receive adjunctive IV dexamethasone (0.15 mg/kg q6h for 2 d), with the initial dexamethasone dose given 20 min before or with the first antibiotic dose. Data concerning the efficacy in adults is less conclusive; one trial demonstrated reduced mortality in pneumococcal meningitis with use of dexamethasone treatment (0.15 mg/kg q6h for 2–4 d). Dexamethasone may reduce penetration of vancomycin into the CSF.

Table 184-2 Antibiotics Used in Empirical Therapy of Bacterial Meningitis and Focal CNS Infections

Table 184-3 Antimicrobial Therapy of CNS Bacterial Infections Based on Pathogena

In cases of meningococcal meningitis, all close contacts should receive chemoprophylaxis with rifampin [600 mg in adults (10 mg/kg in children > 1 year)] q12h for 2 d; rifampin is not recommended in pregnant women. Alternatively, adults can be treated with one dose of ciprofloxacin (750 mg), one dose of azithromycin (500 mg), or one IM dose of ceftriaxone (250 mg).

Complications   Include increased intracranial pressure (ICP), infarction, cerebral sinus or venous thrombosis, seizures, obstructive hydrocephalus, subdural effusion (children), and hearing loss. Moderate or severe neurologic sequelae occur in ~25% of survivors, although the exact incidence varies with the infecting organism.
A focal suppurative infection involving brain parenchyma. Common etiologic agents include mixed flora, aerobic or microaerophilic streptococci, Staphylococcus aureus, aerobic gram-negative bacilli, and anaerobes. Risk factors include sinusitis, otitis, dental infections, head trauma, neurosurgery, and distant foci of infection.
Clinical Features   Solitary abscesses involve frontal > temporal > parietal > cerebellar > occipital lobes of the brain, in decreasing order of frequency. Hematogenous spread of infection to brain frequently results in multiple abscesses. Specific clinical features are shown in Table 184-4.

Table 184-4 Clinical Manifestations of Brain Abscess

Diagnosis   CT and MRI are the most useful diagnostic tools and serve to identify the location and number of abscesses and the presence of associated parameningeal or sinus infection. Typical CT appearance is of a hypodense lesion with a uniformly enhancing ring surrounded by an outer zone of hypodense-appearing edema. Typical features may be absent in early lesions and in pts receiving glucocorticoids. Neoplasms, granulomas, resolving hematomas, and infarcts may resemble abscesses on CT and MRI. LP is contraindicated in pts with suspected or known brain abscess as it rarely adds useful diagnostic information and may precipitate herniation.

Optimal therapy of encapsulated abscesses includes surgical drainage (aspiration or total excision) and antibiotics. Unencapsulated abscesses (“cerebritis”) may respond to antimicrobial therapy alone. Empirical antibiotic therapy should be modified based on the results of abscess cultures. Typical regimens for empirical therapy are shown in Table 184-5; all pts should receive a minimum of 6–8 weeks of parenteral antibiotics. Prophylactic anticonvulsant therapy is also recommended for ³3 months. Short-term glucocorticoid therapy should be used only in pts with proven or suspected elevation in ICP.

Table 184-5 Empirical Therapy of Brain Abscess Based on Source of Infection

A collection of pus between the dural and arachnoid membranes. Major pathogens include aerobic and anaerobic streptococci, staphylococci, and aerobic gram-negative bacilli. Infection may spread to the subdural space through thrombophlebitis of the cranial veins or by contiguous spread of cranial osteomyelitis. Paranasal sinusitis is a major predisposing factor. Other risk factors include otitis, mastoiditis, cranial trauma, neurosurgery, and distant foci of infection.
Clinical Manifestations   Empyema can present as a rapidly progressive life-threatening condition. Signs and symptoms reflect the antecedent infection (e.g., sinusitis), meningeal irritation, the presence of a focal CNS lesion, and increased ICP. These can include fever, headache, nausea and vomiting, declining mental status, focal or generalized seizures, and hemiparesis or hemiplegia.
Diagnosis   CT with contrast enhancement and MRI are diagnostic. Typical CT appearance is an area of crescentic hypodensity beneath the cranium, with a fine line of contrast enhancement between the empyema margin and the subjacent cortex. CT and MRI also help delineate associated otitis or sinusitis. LP rarely adds useful information and is contraindicated because of the risk of herniation.

Subdural empyema is a surgical emergency. Treatment consists of emergent surgical drainage combined with antibiotic treatment. Typical empirical antibiotic regimens include vancomycin plus metronidazole plus ceftriaxone or cefotaxime (Table 184-3 and Table 184-5). Treatment should be continued for a minimum of 4 weeks, with final duration of therapy determined by the pt’s clinical condition and the resolution of infection on neuroimaging studies.


For a more detailed discussion, see Roos KL, Tyler KL: Bacterial Meningitis and Other Suppurative Infections, Chap. 372, p. 2462, in HPIM-15.


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