Bacterial Meningitis

Bacterial meningitis is a disease that presents particular challenges in older adults, with higher mortality than in younger adults. In 1973, Fraser, Henke, and Feldman¹ reported that the mean age of death from meningitis increased from 11.5 years in the period 1935 to 1946 to 64 years during the period from 1959 to 1970. In the latter period, more than one half of all deaths from meningitis occurred in those older than 60 years. The incidence of bacterial meningitis rose from 5 cases per 100,000 to 15 cases per 100,000.¹ Surveys from the late 1970s to the 1980s showed an increasing incidence of meningitis in older patients.^2,3 Between 1998 and 2007, although both the incidence and case fatality of bacterial meningitis fell, reflecting further decline from the previous decades, rates were highest in older adults.⁴

Nosocomial meningitis, particularly related to neurosurgical and neurotologic procedures, is also a cause of the increasing meningitis incidence in this older adults.^4,5 Many of these cases occurred in frail older adults.⁴

Bacteria may reach the subarachnoid space by several different mechanisms.⁴ Remote focal infections can give rise to bacteremia and seed the meninges. This occurs, for example, in patients who have pneumococcal pneumonia and, less frequently, in patients with pyelonephritis and gram-negative meningitis. Meningitis also develops by way of direct meningeal bacterial inoculation during head trauma or after a neurosurgical procedure. Frail older adult patients are especially prone to falls and head injuries.⁶ Meningitis may occur from contiguous spread of infection to the meninges as in patients with otitis media, sinusitis, or mastoiditis. This last mechanism of infection is probably somewhat less common in older adults, compared with younger adults.

Streptococcus pneumoniae remains the most common organism associated with meningitis in older adult patients.⁴ Gram-negative bacilli can cause meningitis in older adult patients both by bacteremic spread of infection, such as in urinary tract infection or pneumonia, and as a nosocomial infection after neurosurgery.^7–9 Escherichia coli is the most common organism to cause meningitis secondary to bacteremic spread. Gram-negative organisms are responsible for 20% to 25% of cases,⁸ implicating infections acquired in health care settings.¹⁰ E. coli and Klebsiella pneumoniae are the more common gram-negative bacilli to cause meningitis after neurosurgery, but more unusual organisms, particularly Acinetobacter, have also been commonly reported.^10,11

Listeria monocytogenes is also more likely to cause meningitis in older people than in younger adults.⁴ Because this infection is T cell mediated, it is possible that known age-associated immune senescence and thymic involution may explain the predisposition of older people to invasive Listeria infection. Although Listeria accounts for 4% to 8% of all cases of meningitis in older people, it is a much rarer cause of meningitis in young healthy adults.⁴ Meningococcal meningitis is the most common cause of meningitis in young adults but a less common cause of meningitis in older people; however, outbreaks have occurred in nursing homes and institutional settings.¹² The incidence of meningococcal meningitis in the older patient population varies from one study to another, mainly reflecting the epidemic nature of the disease. The infection should be considered in older patients who have meningeal signs and have a petechial or macular rash. Often, no focus of infection will be noted.

Skin organisms such as Staphylococcus aureus and coagulase-negative staphylococci, as well as gram-negative bacilli, are responsible for most cases of meningitis secondary to head trauma or neurosurgery. Haemophilus influenzae, a cause of meningitis in children, is much less common in adults and older people and accounted for approximately 7% of cases between 2003 and 2007. When H. influenzae does occur in older patients, it is usually a nonencapsulated variant of the organism.⁴ This is in contrast to children, in whom the type B encapsulated organism is most likely to cause infection. Since the introduction of H. influenzae type B vaccination, rates of invasive disease have decreased substantially. β-Hemolytic streptococci are a relatively rare cause of meningitis in older people but still cause life-threatening infection and meningitis at the extremes of life.¹³

Diagnosing meningitis in older adults can be challenging. Fever and altered mental status are classic, but appear to lack both sensitivity and specificity, and so other features must be evaluated.¹⁴ As detailed in the chapter on delirium, change in mental status often goes unrecognized, and even when it occurs in older people, can be misattributed to dementia, psychosis, transient ischemia, or stroke. In patients who have undergone neurosurgery, postoperative lethargy may be attributed to an expected postoperative course or postoperative pain medication. Mistaken for a musculoskeletal problem, a stiff neck in an older patient may not arouse the same concern that it would in a young adult.

Patients with contiguous infectious sources may complain of localized findings indicative of the initial site of infection, such as ear or facial pain. Subarachnoid space bacteria will cause an inflammatory reaction in the pia and arachnoid matter manifesting as neck pain and stiffness with protective reflexes that, when present, cause the Kernig and Brudzinski signs. Structures that lie within the subarachnoid space are involved in the inflammatory reaction. Pial arteries and veins may become inflamed and cranial nerve roots damaged.

Delirium may also occur. Confusion, headache, or lethargy is a manifestation of this diffuse, inflammatory process. Papilledema, hydrocephalus, and other focal findings may occur as a result of pus occluding the foramina of Luschka and Magendie, resulting in increased intracranial pressure.

It is common for the clinical features of meningitis in older adults to be subtler than in younger adults. This is a recurring theme in almost all studies that involve older patients with meningitis.^13,15–17 Most studies have found that older adult patients with bacterial meningitis are less likely to have neck stiffness and meningeal signs. Challenges to interpretation of the clinical exam in older patients include the presence of degenerative cervical spine disease and poor neck mobility at baseline. In a classic study, Behrman and colleagues¹⁸ found meningismus present in only 58% of older adult patients with meningitis. Even so, older patients with meningitis typically have more mental status abnormalities and are more likely to have seizures, neurologic deficits, and hydrocephalus. A delay in meningitis diagnosis is frequent, which may explain the high mortality rate in this patient group.^13,19

Subacute or chronic meningitis, although rare, is more frequently observed in older patients than in other age groups. Mycobacterium tuberculosis (discussed later) and L. monocytogenes are the most common bacterial causes, and the presentation is most often consistent with basilar meningitis. Individuals may present acutely with decreased level of consciousness, confusion, low-grade temperature, or even seizures, with or without frank meningismus. Often, the patient is not frankly septic but has a moderate inflammatory response that is less fulminant than that observed in other forms of bacterial meningitis. However, a careful history from either the patient or family members will usually provide a subacute picture of chronic headache, decreased appetite, and increased confusion over the course of several weeks. Again, because these symptoms are so nonspecific, it is important to have a high index of suspicion for underlying central nervous system (CNS) infection. New-onset headache in a person without a headache history, especially in the context of constitutional symptoms, should prompt asking about risk factors for tuberculosis (travel, country of origin, personal history of tuberculosis) and listeriosis (undercooked or raw vegetables, outbreak situations, deli meat consumption).

When neck stiffness is the result of meningeal irritation, the neck will resist flexion but can be rotated from side to side. Funduscopic and cranial nerve examination are helpful in identifying associated raised intracranial pressure or brain abscess. Mental status should be carefully described and followed, as increasing lethargy and coma are poor prognostic signs. Examination of the head should include a search for skull fracture, avulsion, or hematoma. Careful otoscopic examination is also a necessity, as otitis media can be missed. Older people can have pneumonia and concomitant meningitis. Indeed, with only mild respiratory symptoms, the physical examination may be the first indication of pneumonia. Cardiovascular examination may detect under­lying valvular heart disease predisposing to endocarditis with meningeal seeding. Examination for costovertebral tenderness, decubitus ulcers, and petechial lesions also provide important information about the source and possible causal agent in meningitis.

Timely lumbar puncture is critical to the diagnosis of bacterial meningitis in both young and old individuals. The routine use of neuroimaging (computed tomography [CT]) before lumbar puncture is controversial.²⁰ A substantial minority of older adult patients with meningitis have focal neurologic findings, and because lumbar puncture is contraindicated in patients with brain abscess, imaging is necessary in these older patients. However, the high mortality rate from meningitis in older adults makes early diagnosis and treatment essential. In consequence, many infectious disease experts now support the strategy of beginning empirical antibiotic therapy pending lumbar puncture, particularly when a delay of hours is anticipated because of imaging delays.^17,21 Some meningitis management guidelines do not always require imaging before lumbar puncture, and this change was associated with a reduction in overall mortality, but follow-up correspondence shows that this is not without controversy.^22–24 In general, if focal neurologic deficits exist or cannot be reasonably assessed, CT before lumbar puncture is reasonable. However, treatment should NOT be delayed pending the diagnostic tests. It is very unlikely that antimicrobial therapy will significantly alter lumbar puncture results within several hours, and enhanced molecular microbiologic techniques can still provide a diagnostic answer if the patient has started antibiotics.

Regarding lumbar puncture, online videos are helpful for novices, even when supervised by experienced operators. Understanding the anatomy is essential, and a series of YouTube videos posted by Raeburn Forbes (www.youtube.com/watch?v=cpl0Zb2p_wA) are a useful resource. A review suggests that small-gauge, atraumatic needles may decrease the risk of headache after diagnostic lumbar puncture, as does reinsertion of the stylet before needle removal.²⁵

There is very little literature to suggest that cerebrospinal fluid (CSF) findings differ between older and younger patients with bacterial meningitis. Lumbar puncture will show purulent fluid with white blood cell counts between approximately 500 and 10,000 cells/mm.³ Polymorphonuclear leukocytes predominate, usually comprising more than 90% of total cell count. Meningitis caused by L. monocytogenes, M. tuberculosis, or viruses have a mononuclear cell predominance. At least one study has shown that older adult patients with meningitis are more likely to have a diminished CSF cellular response than younger adults,²⁶ and those with low cell counts but many bacteria on the Gram stain have a poor prognosis. CSF glucose levels are usually low in patients with bacterial meningitis, with CSF to serum glucose ratios less than 50%. Spinal fluid protein is elevated (>50 mg/dL), and very high protein levels are associated with poor prognosis.

CSF Gram stain will be positive for bacteria in 60% to 90% of all patients with meningitis.¹⁴ In a study by Behrman and colleagues,¹⁸ only 50% of older adult patients with meningitis had a positive Gram stain, and the Gram stain is most likely to be negative in patients who have received prior antibiotic therapy. In those patients whose Gram stain is negative, a variety of methods to detect bacterial antigen are now in common use; these include latex fixation, coagglutination, and 16S ribosomal RNA (rRNA) polymerase chain reaction (PCR). Blood cultures are recommended in all patients in whom bacterial meningitis is suspected because almost one half of all older adult patients with meningitis have concomitant bacteremia.¹⁸ In addition, sputum, urine, and wound cultures may be extremely helpful in determining causal agents and source of infection.

The treatment of bacterial meningitis requires prompt initiation of appropriate antibiotic therapy. The antibiotic chosen should be bactericidal for the causal agent and must diffuse across the blood-brain barrier. Table 68-1 lists the causal agent and the antibiotic generally recommended. Information from the history and physical examination, in combination with a careful review of the CSF Gram stain, is the foundation on which the causal agent will be determined and the optimal antibiotic chosen. Although in general a parsimonious approach to consultation serves many frail older adults well, an infectious disease specialist, when possible, should be involved in the case as the mortality rate from the disease is high and the margin of error is small, and the involvement of an infectious disease specialist appears to be beneficial.²⁷ The specific epidemiology of the patient’s hospital or community will take on increasing importance in determining the antibiotic choice. Given the rising incidence of high-level penicillin-resistant organisms, empirical therapy of pneumococcal and neisserial meningitis should include vancomycin and a third-generation cephalosporin.

Staphylococcus aureus can be a particular treatment challenge and is seen in settings both of hematogenous spread²⁸ and postoperatively, where it can be the most common cause of meningitis after neurosurgery in older adults.²⁹ Of note is the reported shift from methicillin-sensitive strains to methicillin-resistant S. aureus (MRSA) strains³⁰ in some countries and institutional settings. The latter necessitate use of such medications as linezolid, trimethoprim-sulfamethoxazole, daptomycin, or vancomycin.^31,32

The role of adjunctive corticosteroid therapy in acute bacterial meningitis in adults with suspected or confirmed pneumococcal meningitis is nuanced. There is discussion that release of bacterial components by the invading pathogen, and the inflammatory reactions that they promote, is the source of secondary systemic and intracranial complications contributing to the high mortality. In consequence, strategies that might inhibit bacterial lysis, or at least not promote it, are being pursued.³³ Included in this is likely to be a reevaluation of the use of corticosteroids as adjuvant treatment and the development of treatment strategies that use antibiotics that are bactericidal but not bacteriolytic.¹⁹ Until further information is available, dexamethasone is associated with decreased sepsis-related mortality in acute S. pneumoniae meningitis (de Gans). Therefore, in the empirical setting, dexamethasone 0.15 mg/kg body weight every 6 hours is recommended, with the first dose 15 to 20 minutes prior to the first dose of antibiotics.³⁴ When cultures are available, if the organism is a bacterium other than S. pneumoniae or M. tuberculosis, steroids should be discontinued.

Older adult patients with meningitis may be admitted to an intermediate or intensive care unit, where vital signs and neurologic status can be carefully monitored. Some patients are severely dehydrated or volume depleted, and others have septic shock. Colloids or crystalloids may be necessary to improve blood pressure and urine output. In an evolving literature, there is some support for crystalloids, especially with so-called balanced fluids such as Ringer’s lactate compared with normal saline, but the generalizability to frail older adults is not known.³⁵ Inappropriate antidiuretic hormone secretion may accompany CNS infections but should be self-limited if hypotonic solutions are avoided.

The comatose older adult patient requires specialized care in the critical care setting. The patient may need frequent suctioning, particularly if pneumonia is present, secondary to potentially limited pulmonary hygiene in the context of advanced age or underlying structural lung disease such as emphysema. The patient should be turned frequently to prevent decubitus ulcers, and an airbed should be considered in all individuals, particularly those with elevated body mass index, poor preexisting nutritional status, and underlying skin disease. A condom catheter is preferable to a Foley catheter, unless urinary retention develops. In patients who develop relapsing or prolonged fever, a repeat lumbar puncture is necessary. Drug fever, phlebitis, urinary tract infection, intravenous and central lines, and pulmonary emboli are all possible explanations for prolonged fever.

The currently available pneumococcal vaccine is routinely recommended in all patients older than 65 years of age. Although there are no specific data to support the prevention of pneumococcal meningitis in older adults, it is clear that the vaccine decreases the incidence of serious pneumococcal respiratory infection. Because most cases of pneumococcal meningitis in older patients are associated with pneumonia as the initial infection, vaccination in older adult patients would be of benefit in preventing meningitis.