A passive survey conducted in the United States between 1978 and 1981 revealed an annual incidence rate for bacterial meningitis of 3.0 cases per 100,000 population.¹ During this period, bacterial meningitis was predominantly a disease of children, the most common offending pathogen being Haemophilus influenzae. The introduction of routine immunization of children against H. influenzae type B in the late 1980s dramatically reduced the incidence of infection with this microorganism. A consequence was a decrease in the overall incidence of bacterial meningitis and particularly in meningitis caused by H. influenzae, so that bacterial meningitis is now a disease predominantly of adults.²

Pathophysiology

The initial event is usually nasopharyngeal colonization with a pathogenic microorganism.³ This is followed by mucosal invasion, bacteremia, and meningeal invasion.⁴ A marked inflammatory response occurs in the subarachnoid space, but this response is inadequate to control the infection. This inflammatory response results in increased permeability of the blood-brain barrier. This is responsible for the increased cerebrospinal fluid (CSF) protein content seen in patients with meningitis. Progression of meningitis leads to the development of cerebral edema, resulting in increased CSF pressure. Inflammation of blood vessels traversing the subarachnoid space may lead to their thrombosis. This can result in ischemia and infarction of the underlying brain.

Clinical Presentation

Patients with acute bacterial meningitis usually present with headache, neck stiffness, fever, projectile vomiting, and photophobia. In more advanced disease, there is progressive clouding of consciousness. On examination, neck rigidity may be seen and Kernig’s and Brudzinski’s signs may be elicited. Cranial nerve palsies or focal neurologic signs may be seen in a minority of patients. The presence of petechial skin lesions should raise suspicion for meningococcemia.

Diagnosis

The differential diagnosis includes viral and tuberculous meningitis, viral meningoencephalitis, subarachnoid hemorrhage, and primary amebic meningoencephalitis. Differentiation from viral meningitis on clinical grounds is usually difficult, and requires laboratory testing. Where tuberculosis is prevalent, it must be recognized that tuberculous meningitis can sometimes manifest acutely and could be mistaken for bacterial meningitis. Viral meningoencephalitis may manifest somewhat similarly with headache and fever, but patients would usually have more profound alteration in the sensorium early in the illness and neck stiffness may not be prominent. The most prominent symptom of subarachnoid hemorrhage is a severe headache with a rapid onset. Primary amebic meningoencephalitis is a rare condition with a presentation similar to that of acute bacterial meningitis, but cultures are negative and amebae can be detected in the CSF by careful microscopic examination. There is usually a recent history of swimming in a warm freshwater lake or pond.

The most important diagnostic test is a lumbar puncture, which should always be performed in all patients with suspected acute meningitis. Imaging tests do not help in making the diagnosis or identifying the cause of bacterial meningitis. It is not necessary to obtain a computed tomography (CT) scan before performing a lumbar puncture unless there are focal neurologic deficits.⁵ The CSF should be sent for cell count, protein and glucose levels, and Gram staining and culture. Typical CSF findings in acute bacterial meningitis are an elevated opening pressure, increased CSF white blood cell (WBC) count (100-10,000 cells/µL), usually with a predominance of neutrophils, increased CSF protein level (>50 mg/dL) and decreased CSF glucose level (<40% of simultaneously measured serum glucose level).⁶ Gram staining may reveal the presence of microorganisms and, if so detected, would be helpful for guiding therapy. In viral meningitis, the CSF WBC count is elevated, but the cells are usually predominantly lymphocytes, and the CSF glucose level may be normal or marginally decreased. The best way to confirm a diagnosis of viral meningitis is by specific polymerase chain reaction (PCR) testing, if available.

Treatment

The management of bacterial meningitis includes appropriate antibiotic therapy and adjunctive corticosteroids.^7,⁸ Ideally, the lumbar puncture should be done before the administration of antibiotics. However, if there is a delay in performing the lumbar puncture for any reason, antibiotic administration should not be delayed. A lumbar puncture should be performed as soon as possible, even if antibiotics have already been administered; the possibility of being able to make a definite causative diagnosis, and its value in guiding subsequent therapy and managing possible complications, are fully worth the effort. Empirical antibiotics should be selected based on the expected pathogens. The patient’s age, presence or absence of risk factors such as middle ear or sinus disease, or recent neurosurgery provide clues about the cause and pathogenesis.

It is recommended that patients be started on adjunctive dexamethasone 10 mg IV every 6 hours for 4 days with the first dose of antibiotics, because this has been shown to improve outcomes in bacterial meningitis.⁷ Antibiotic selection and dosing should also take into consideration the ability to cross the blood-brain barrier and achieve an effective concentration in the CSF. In adults, initial empirical treatment should provide adequate therapy for Streptococcus pneumoniae and Neisseria meningitidis. Increasing resistance of S. pneumoniae to beta-lactam antibiotics (including ceftriaxone) has prompted recommendations to initiate empirical antibiotic therapy with a regimen consisting of vancomycin and ceftriaxone.⁶ If Listeria monocytogenes is a possibility (e.g., in older adults, pregnant women, and those with cellular immune deficits), ampicillin should be added. If Pseudomonas aeruginosa is a possibility, as after neurosurgical procedures, ceftazidime should be used instead of ceftriaxone. Antibiotic therapy should be adjusted once the causative microorganism has been identified. Duration of therapy for bacterial meningitis has not been adequately defined. For meningococcal meningitis, 7 days of therapy is considered adequate. S. pneumoniae should be treated for 10 to 14 days. L. monocytogenes should be treated for at least 21 days.⁹

ACUTE MENINGOCOCCEMIA

Definition, Etiology, and Incidence

Acute meningococcemia is a disseminated infection caused by Neisseria meningitidis, with high mortality rates in those with fulminant disease. Meningococcal infection occurs in an endemic pattern, with periodic epidemics. There are substantial cyclic variations in disease incidence. In the United States, epidemics account for less than 5% of the reported cases. The incidence of meningococcal disease in the United States peaked at 1.7 cases per 100,000 population in 1997.¹⁰

Pathophysiology

The pathogenesis of meningococcal infection begins with nasopharyngeal colonization. About 10% of the population has asymptomatic nasopharyngeal carriage of N. meningitidis during nonepidemic periods. A small proportion of carriers go on to develop invasive meningococcal disease. People who develop invasive disease generally do so soon after acquisition of carriage.¹¹ Factors that facilitate invasive disease include agent factors such as virulence and transmissibility and host factors.

Deficiencies of the late components of the complement pathway place individuals at markedly increased risk of developing meningococcal infections.¹² These patients have recurrent episodes of meningococcal infection. Genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates the MBL pathway of complement activation, may also predispose to increased susceptibility to meningococcal infections.¹³

Clinical Presentation

Meningococcal infection may manifest in different forms: bacteremia without sepsis, meningitis (with or without meningococcemia), acute meningococcemia (with or without meningitis), a meningoencephalitic picture, or chronic meningococcemia. The most fulminant form is acute meningococcemia, in which death may ensue within hours of the onset of symptoms.

The most common manifestation of acute meningococcemia is fever with rash. The rash usually begins as a petechial rash, initially with a few discrete lesions 1 to 2 mm in diameter, which often progress and coalesce to form larger ecchymotic lesions (Fig. 1). If there is associated meningitis, meningeal signs and symptoms may also be present.

Figure 1 Classic rash of patient with meningococcemia.

The shock state is a dominant feature in patients with acute meningococcemia, and is often accompanied by disseminated intravascular coagulation (DIC). Meningococcemia can lead to complications such as massive adrenal hemorrhage, DIC, arthritis, heart problems such as pericarditis and myocarditis, neurologic problems such as deafness and peripheral neuropathy, and peripheral gangrene.¹⁴ In epidemic settings in third-world countries, case-fatality rates as high as 70% have been recorded. In endemic settings in industrialized countries, the mortality rate is approximately 8%, but could be as high as 19%.

Meningococcemia does not always manifest in a fulminant manner. An unusual manifestation of meningococcal infection is chronic meningococcemia, which manifests with low-grade fever, rash, and arthritis. This manifestation is identical to that of chronic gonococcemia.

Diagnosis

When patients present with an acute febrile illness with the characteristic ecchymotic rash, the diagnosis is not difficult to make. Early infection could be missed if a careful physical examination is not carried out in a patient with an acute febrile illness. Definitive diagnosis requires isolation of the microorganism from a normally sterile site. Samples for blood cultures should always be obtained before the administration of antibiotics, if possible. Antibiotic therapy rapidly sterilizes the blood and CSF in patients with meningococcal infection.^15,¹⁶ CSF cultures are often positive for microorganisms, even in patients who do not have clinical evidence of meningitis,¹⁷ and should always be examined when meningococcemia is suspected. Microorganisms may also be identified in the biopsy of petechial skin lesions.

Treatment

The treatment of acute meningococcemia involves appropriate antibiotic therapy, along with supportive therapy for shock, heart failure, DIC, and other complications. Early antibiotic therapy has been conclusively shown to improve outcomes in patients with meningococcal disease.¹⁸ The recommended treatment for severe meningococcal infection is a third-generation cephalosporin with good CSF penetration. Ceftriaxone, 1 g every 12 hours, is the most commonly used treatment.¹⁹ Cefotaxime and ceftazidime should be equally efficacious alternatives. Patients allergic to cephalosporins may be treated with chloramphenicol, 100 mg/kg, in four divided doses, up to a total dosage of 4 g/day.²⁰ High doses of penicillin G should also usually be adequate; however, small numbers of resistant N. meningitidis have been reported, and penicillin G should therefore not ordinarily be the first choice of antibiotic in the absence of susceptibility data. The shock state is a dominant part of the clinical picture of meningococcemia and supportive management is important. The use of steroids for meningococcemia is controversial, and a recommendation for its routine use for treatment of this condition cannot be made.

Prophylaxis

Household contacts are at significantly higher risk of infection.²¹ Chemoprophylaxis is recommended for household contacts, daycare center staff and clients, and anyone exposed to the patient’s oral secretions. For health care workers, this would include persons who intubated the patient and who provided suction to clear secretions. Effective prophylactic treatments include a single 1-g dose of ceftriaxone intravenously or intramuscularly, a single 500-mg dose of ciprofloxacin, a single 500-mg dose of azithromycin, and 600 mg of rifampin every 12 hours for 2 days.¹⁸

CRANIAL SUBDURAL EMPYEMA

Definition, Etiology, and Incidence

Subdural empyema is a condition in which there is collection of pus in the region between the dura and the arachnoid. The most common causes of subdural empyema are aerobic and anaerobic streptococci (especially the S. milleri group), Staphylococcus aureus and, to a lesser extent, aerobic gram-negative bacilli.^22,²³ Studies have found anaerobic infections in varying proportions of infections, with high proportion of patients having anaerobic microorganisms recovered in some studies with careful culturing.²⁴ This raises the possibility that these infections are usually polymicrobial, with anaerobic microorganisms usually present. Subdural empyemas account for 15% to 20% of all localized intracranial infections.²³

Pathophysiology

Cranial subdural empyema is usually a complication of infection of the paranasal sinuses.²³ Less commonly, it results from spread from the middle ear.²⁵ It may also occur as a complication of trauma or neurosurgery. Infection spreads intracranially through the emissary veins that communicate between the veins draining the facial structures and intracranial venous channels. In a small proportion of cases, subdural empyema may occur by metastatic spread, usually from a pulmonary infection, for an unexplained reason.