CASE STUDIES IN INFECTIOUS DISEASE

Bacterial Meningitis: Would You Miss This Diagnosis?

When the presentation is classic, you are unlikely to overlook this life-threatening disorder, but in many cases you will need to rely on more elusive clues to confirm the diagnosis.

By Natalie C. Klein, MD, and Burke A. Cunha, MD

Bacterial meningitis is a life-threatening medical emergency that requires immediate diagnosis and therapy. The diagnosis is rarely missed if the patient presents with the classic picture of fever, headache, rash, nuchal rigidity, and a Kernig or Brudzinski sign, but it may be less obvious in elderly or debilitated patients and neonates, who may not exhibit the characteristic findings. Bacterial meningitis should be suspected in anyone who has a change in mental status, a new seizure, a sudden onset of any central nervous system disorder, or a petechial rash.

Early in the disease, the patient may report only a mild flulike illness, myalgia of the neck or head, or symptoms suggestive of a viral illness. Although most people with bacterial meningitis appear sicker than those with viral meningitis, clinical differentiation may be difficult-if not impossible-in some cases. You must therefore perform a diagnostic evaluation whenever you suspect meningitis.

CASE REPORT

A 38-year-old woman with no significant previous medical history came to the emergency department with a complaint of mild sore throat that had persisted for three days, accompanied by arthralgia, myalgia, and low-grade fever. The day before, she had had a severe headache with neck stiffness, nausea, and vomiting. She claimed not to have a cough, shortness of breath, abdominal pain, diarrhea, or urinary tract symptoms. She had no history of tick exposure or skin rash, was not taking any medications, had no known drug allergies, and did not smoke. She lived with her husband and two children, all of whom were well.

On physical examination, she was thin, alert, and oriented but had an inappropriate affect. Her temperature was 98.6°F; pulse, 100; respirations, 20; and blood pressure, 110/70 mm Hg. Her neck was stiff, but Kernig and Brudzinski signs were not present. The pharynx was slightly injected but without exudate. Findings on heart and lung examination were normal. No rash was present. The neurologic examination revealed intact cranial nerves, normal reflexes, and no sensory or motor deficits. Her white blood cell count was 21,800/mm3 with 67% polymorphonuclear leukocytes and 26% band cells. Platelet count was 200,000/mm3. Electrolyte levels were within normal range, and the glucose level was 131 mg/dL. A chest film showed no signs of pneumonia. A lumbar puncture revealed clear cerebrospinal fluid (CSF) with a glucose level of 88 mg/dL and a total protein level of 33 mg/dL and no cells.

The patient underwent intravenous hydration after she was admitted with a diagnosis of meningismus, accompanied by the instruction to "rule out early viral meningitis versus viral syndrome." Approximately 12 hours later, she became acutely lethargic and a second spinal tap was performed. The CSF appeared cloudy and now contained 871 white blood cells, of which 93% were polymorphonuclear leukocytes; the glucose level was 1 mg/dL; the total protein level, 417 mg/dL. Gram stain revealed rare gram-negative diplococci, the latex agglutination test for bacterial antigens was positive for Neisseria meningitidis, and both the original and repeated CSF cultures grew N. meningitidis.

The patient was given high-dose intravenous penicillin G, 24 million units a day, and was transferred to the medical intensive care unit for observation. Despite the 12-hour delay in diagnosis, she recovered completely. Intimate household contacts received prophylactic rifampin, and the patient was given rifampin before discharge to eliminate nasopharyngeal carriage of Neisseria.

CASE DESCUSSION

This case highlights several important clinical clues to the diagnosis of bacterial meningitis. The onset is often subacute, with a preceding upper respiratory tract infection-as in this case-but the presentation can also be more acute, with signs and symptoms of meningitis developing within less than 24 hours. You should consider the diagnosis of meningitis whenever a patient complains of severe headache and neck stiffness. The absence of a rash is not significant, because the classic petechial eruption may not develop in as many as half of patients with meningococcal meningitis. The physical examination in this case provided two clues to the diagnosis: nuchal rigidity and-most important-an inappropriate affect, although the patient was alert and oriented. Meningitis should always be considered in the differential diagnosis of a patient with an unexplained change in mental status.

The laboratory studies revealed an elevated white blood cell count with a large percentage of band cells. The platelet count was normal, although in some cases-especially in instances of meningococcal disease-you may see thrombocytopenia. The initial CSF findings were normal, but the emergency physician nevertheless entertained the diagnosis of meningitis and admitted the patient for observation.

Classic bacterial meningitis developed 12 hours later, with a turbid CSF containing predominantly polymorphonuclear leukocytes with depressed glucose and elevated protein levels. Gram stain of the second CSF specimen showed gram-negative diplococci, and both CSF specimens grew N. meningitidis. This case demonstrates the point that CSF culture and Gram stain may be positive very early in bacterial meningitis, before an inflammatory response develops.

Luckily, the patient did well on high-dose penicillin therapy despite the delay in diagnosis. Prophylactic rifampin-or a single dose of ciprofloxacin or levofloxacin-must be given to intimate household and hospital contacts of patients with meningococcal or Haemophilus influenzae meningitis and to the index case as well to eradicate nasopharyngeal carriage of meningococcus.

BACTERIOLOGY AND PATHOPHYSIOLOGY

Streptococcus pneumoniae, N. meningitidis, and H. influenzae account for approximately 70% to 80% of all cases of meningitis. Although S. pneumoniae is the most common cause of meningitis in adults, N. meningitidis is the most common cause in children, followed by S. pneumoniae (see table below). With widespread use of H. influenzae type b vaccine, the incidence of H. influenzae meningitis has decreased. Escherichia coli and group B streptococci are the most common causes of meningitis in neonates, followed by Listeria monocytogenes and S. pneumoniae.

Bacterial meningitis usually occurs in an otherwise healthy host, but a variety of predisposing factors or clinical situations may contribute to the development of a specific type of meningitis (see table below). Neurosurgical procedures can predispose patients to bacterial meningitis, as can such disorders and conditions as otitis media, sinusitis, mastoiditis, head trauma, immunosuppression, sickle cell anemia, and asplenia. Although bacterial meningitis is most frequently acquired after bacteremia, it can also develop by contiguous spread from an intracranial focus or paranasal infection or by traumatic inoculation of bacteria into the central nervous system.

DIAGNOSIS

Laboratory findings. The definitive diagnosis of bacterial meningitis depends on the results of examination of the CSF (see table below). A number of tests are available for CSF evaluation. If only a small amount of fluid is obtained, the most important tests for diagnosing meningitis are the Gram stain and culture. A Gram stain smear of the spun sediment of CSF reveals the causative agent in 70% to 80% of cases and is positive in 80% to 90% of patients with bacterial meningitis. Bacterial antigens can be detected rapidly by latex agglutination or by countercurrent immunoelectrophoreses. These tests can also aid in the diagnosis of meningitis caused by H. influenzae type b, pneumococcal, meningococcal, group B streptococcal, and E. coli pathogens, especially when the Gram stain is negative.

Normal CSF contains fewer than five lymphocytes, a glucose level greater than 50% of the serum glucose, and a protein content less than 45 mg/dL. Once the CSF cell count and differential and glucose level have been determined, the CSF abnormalities can be classified into one of three patterns (see table below).

Differential diagnosis. Although predisposing conditions and risks to which a patient has been exposed are helpful in predicting the causative pathogen in documented meningitis, what first must be determined is whether the patient actually has bacterial meningitis or a mimicking condition. The most common diagnostic problem is having to distinguish between pyogenic meningitis and viral meningitis. As already noted, patients with viral meningitis usually appear less ill than those with bacterial meningitis. Further, meningitis caused by enteroviruses tends to have a seasonal distribution and may be accompanied by a maculopapular rash, diarrhea, or sore throat. In such cases the CSF Gram stain is negative, the glucose level is usually normal, and the cells are predominantly lymphocytes.

Bacterial endocarditis may mimic acute bacterial meningitis clinically, and the initial spinal tap results may be indistinguishable from CSF findings in pyogenic meningitis. Other possible mimics are chemical meningitis, early tuberculous meningitis, parameningeal foci secondary to other lesions, amebic meningoencephalitis, carcinomatous meningitis, Lyme disease, herpes encephalitis, sarcoid meningitis, and cerebral toxoplasmosis (see table below).

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