Acute community-acquired bacterial meningitis in adults: An evidence-based review

MICROBIOLOGY: WHEN TO SUSPECT DIFFERENT ORGANISMS

S pneumoniae: The most common cause in adults

Patients without a spleen and patients with either a primary or secondary immunoglobulin deficiency, including patients with multiple myeloma or human immunodeficiency virus infection, are at a higher risk of infection with this organism.

N meningitidis: More common in young adults

N meningitidis is easily transmitted and is associated with crowding, as in school dormitories and military barracks. People with congenital deficiencies of components of terminal complement are at greater risk for both meningococcal and gonococcal infections. Patients with recurrent episodes of Neisseria infection should be evaluated for complement deficiency.

Photos courtesy of Thomas Fraser, MD.

Meningococcal infection is more commonly associated with a rash. The most common rash of meningococcal meningitis is a very transient, maculopapular rash that appears early in the course of the disease. More pathognomonic is a petechial rash (Figure 1) with thrombocytopenia, which can very rapidly progress to purpura, ecchymosis, and disseminated intravascular coagulation. The petechial rash is evident in 60% of adults and up to 90% of children,⁷ and it is most likely to appear in dependent areas (such as the back of a patient lying down) and in areas of pressure, such as under the elastic band of underwear or stockings.

Listeria

Listeria infection is usually acquired through contaminated food such as raw vegetables, unpasteurized milk and cheese, and deli meats. From the gastrointestinal tract, it spreads to the bloodstream and then to the meninges.

Listeria is an intracellular pathogen; thus, people at greater risk are those with poor cell-mediated immunity due to immunosuppressant medications such as steroids or tumor necrosis factor inhibitors.

The rate of Listeria meningitis starts to increase with age, especially after age 50, probably due to immune senescence or decreased immunity with age.

Aerobic gram-negative bacilli

Gram-negative enteric bacilli usually cause meningitis after head trauma or neurosurgery and are very uncommon causes of community-acquired meningitis. Disseminated strongyloidiasis, also known as hyperinfection syndrome, should be suspected in any patient with community-acquired meningitis caused by enteric gram-negative bacilli.

Strongyloides stercoralis is a parasitic intestinal roundworm that is found in the tropics, in the subtropics, and in certain parts of the United States and Europe. The adult worm lives in the intestines and lays eggs, which hatch in the mucosa; the larvae are excreted in the stool. A small percentage of larvae penetrate the perianal skin and gut mucosa to cause an autoinfection. People may asymptomatically harbor the parasite for decades, then develop the hyperinfection syndrome when treated with immunosuppressive drugs such as steroids. In the hyperinfection syndrome a significant proportion of the larvae penetrate the gut mucosa to enter the bloodstream and travel throughout the body, including into the brain, carrying gram-negative bacteria with them.

The mortality rate of untreated hyperinfection syndrome can sometimes reach 100%.⁸ Thus, it is important to identify and treat the hyperinfection syndrome in the context of gram-negative bacillary meningitis.

SUSPECTED MENINGITIS: CLINICAL SCENARIO

A 36-year-old man presents to the emergency department with high fever, headache, and lethargy that developed over the past 24 hours. His temperature is 104°F (40°C), pulse 120 beats/min, respiratory rate 30/min, and blood pressure 130/70 mm Hg. He is oriented only to person and has nuchal rigidity. His white blood cell count is 30 × 10⁹/L, with 20% bands.

The clinical questions that arise with such a patient are:

• Does the patient have bacterial or viral meningitis?
• Can we reliably rule out meningitis based on a history and physical examination?
• Is a lumbar puncture for cerebrospinal fluid (CSF) analysis needed? How should these studies be interpreted?
• Should computed tomography of the head be done before lumbar puncture?
• Which antimicrobial drugs should be started empirically at the outset?
• What is the role of steroids in treatment?

CLINICAL SIGNS AND SYMPTOMS

The classic triad of meningitis is fever, neck stiffness, and altered mental status. Other signs and symptoms that have been described are photophobia, headache, nausea, vomiting, focal neurologic symptoms, altered mental status, the Kernig sign (inability to allow full knee extension when the hip is flexed to a 90° angle), and the Brudzinski sign (spontaneous flexion of the hips during attempted passive flexion of the neck).

Can meningitis be ruled out if the patient does not have this classic presentation?

Unfortunately, only a few high-quality studies of the diagnostic accuracy of signs and symptoms of bacterial meningitis have been done. Fourteen retrospective studies examined this issue, but they were heterogeneous with respect to patient age, immunosuppression status, and clinical presentation, as well as to how meningitis was diagnosed (via culture or cerebrospinal fluid analysis), making the results difficult to interpret.⁹ Retrospective studies are more prone to bias, as they lack a control group, and examiner bias is more likely. Based on retrospective data, the combination of fever, neck stiffness, and altered mental status has a sensitivity of only 0.46.⁹

Two prospective studies examined symptoms and signs. Thomas et al¹⁰ evaluated 297 patients with “clinically suspected meningitis.” Unfortunately, in this study the physical examination was not standardized. In a study by Uchihara and Tsukagoshi,¹¹ the measurement was more reliable, as they used a single examiner to evaluate patients presenting with fever and headache, but only 54 patients were studied.

Based on these prospective studies, the presence of nausea and vomiting, headache, or neck stiffness does not reliably rule in meningitis (Table 1).⁹ Similarly, the absence of these does not rule it out. The 95% confidence intervals (CIs) of the positive and negative likelihood ratios include the value 1. (A simple interpretation of that would be that the likelihood of finding these features is the same in patients with meningitis when compared with those without meningitis.⁹)

For the physical examination, the presence or absence of fever, the Kernig sign, or the Brudzinski sign were also inconclusive. The CIs of the positive and negative likelihood ratios, like those of the symptoms, included the value 1. Only one test done on physical examination looked promising in having diagnostic utility to rule out meningitis: the jolt accentuation test (performed by asking a patient with a headache to quickly move his or her head twice horizontally; the result is positive if the headache worsens). If the result is negative, meningitis is unlikely (negative likelihood ratio 0.05, 95% CI 0.01–0.35).⁹ However, a positive test is not useful in making the diagnosis. A caveat is that this is based on a single study.

In summary, the history and physical examination are not sufficient to determine whether a patient has meningitis. If a patient is suspected of having meningitis, a lumbar puncture is needed.