INTRODUCTION — In the pre-antibiotic era, bacterial meningitis due to Streptococcus pneumoniae and Haemophilus influenzae was virtually 100 percent fatal. With the advent of antibiotics, the mortality for H. influenzae and Neisseria meningitidis infections decreased to <10 percent, and that of S. pneumoniae to 30 percent [1]. Mortality due to S. pneumoniae meningitis in high-income countries has further decreased with the use of adjunctive steroids [2]. Meningitis remains an important global health disease despite the effectiveness of current antibiotics as well as the availability of conjugate vaccines for the three most common meningeal pathogens [3,4].
The epidemiology of bacterial meningitis in adults will be reviewed here. The pathogenesis, clinical features, treatment, prognosis, and prevention of bacterial meningitis in adults and children and issues related to chronic and recurrent meningitis are discussed separately. (See "Pathogenesis and pathophysiology of bacterial meningitis" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Approach to the patient with chronic meningitis" and "Approach to the adult with recurrent infections", section on 'Meningitis'.)
COMMUNITY-ACQUIRED MENINGITIS
Incidence
United States — S. pneumoniae and N. meningitidis are the two major organisms causing community-acquired meningitis (table 1) [5-7]. The high frequency of pneumococcal meningitis in adults reflects the relatively high rate of pneumococcal infection in the community.
In the United States and other countries, following the institution of routine infant immunization with the conjugate H. influenzae type b vaccine in 1990 and the 7-valent S. pneumoniae (pneumococcus) conjugate vaccine in 2000, followed by the 13-valent pneumococcal vaccine (PCV13) in 2010, bacterial meningitis decreased in frequency, and the peak incidence of bacterial meningitis has shifted from children under five years of age to adults (figure 1) [5,8,9]. The frequency with which various bacteria cause meningitis in children is discussed separately [6,7]. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Epidemiology'.)
It has been estimated that meningitis occurs in only 4 percent of invasive pneumococcal infections, compared with 48 percent of invasive N. meningitidis infections, 30 percent of invasive listeriosis, 10 percent of invasive H. influenzae infections, and 4 percent of invasive group B streptococcal infections [10]. (See "Pneumococcal pneumonia in patients requiring hospitalization" and "Clinical manifestations of meningococcal infection" and "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)
●S. pneumoniae – In a population-based observational study between 1997 and 2010 in the United States, the most common identifiable pathogen was S. pneumoniae (21,858 cases) with an incidence of 0.306 cases per 100,000 people [6]. With the introduction of the PCV13 in 2010, the number of cases in the United States remained unchanged, although the proportion of cases caused by serotypes in the vaccine decreased significantly [11]. A subsequent 16-year prospective study in France showed a reduction in the incidence of pneumococcal meningitis in children after the implementation of PCV13, but with a sharp increase in cases in the last two years of the study due to serotype 24F, which is not present in the current vaccine [12]. The impact of PCV on invasive pneumococcal disease in adults is discussed in greater detail separately. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia", section on 'Impact of childhood vaccination'.)
Another important trend has been the increase in incidence of penicillin-resistant S. pneumoniae meningitis worldwide. This is discussed in detail separately. (See "Treatment of bacterial meningitis caused by specific pathogens in adults", section on 'Streptococcus pneumoniae' and "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Microbiology and pathogenesis of Streptococcus pneumoniae".)
●N. meningitidis – The incidence of Neisseria meningitidis infection has decreased likely associated with meningococcal vaccination in the United States and now occurs at rates close to common bacterial causes of nosocomial meningitis such as staphylococcus, gram-negative bacteria, and H. influenzae [6]. In 2018, the incidence of meningococcal disease was 0.10 per 100,000 persons [7].
●H. influenzae type b – In a population-based observational study in the United States (1997 to 2010), the incidence of H. influenzae meningitis decreased from 0.10 to 0.058 per 100,000 people [6]. A more recent study of 694 infants with meningitis admitted to a large pediatric hospital between 2010 and 2017 found only one case of H. influenzae [13]. This marked decrease is presumed due to widespread vaccination of infants. Strains other than type b continue to cause occasional invasive infection (including meningitis) in children and adults. In an epidemiologic study of H. influenzae disease in children, an increase of invasive H. influenzae disease was noted and mainly caused by nontypeable and type a strains [14]
Global — S. pneumoniae remains the most common etiology globally, accounting for approximately 25 to 41 percent of cases [4]. In a prospective review of 1412 episodes of community-acquired bacterial meningitis in the Netherlands from 2006 to 2014, S. pneumoniae was responsible for 51 percent, N. meningitidis for 37 percent, and L. monocytogenes for 4 percent of cases [9]. The remaining cases were primarily due to H. influenzae, streptococci, Staphylococcus aureus, and gram-negative bacilli.
The distribution of pathogens depends upon the region of the world. As an example, large epidemics of meningitis due to N. meningitidis serogroup A used to occur in sub-Saharan Africa. Although the implementation of the meningococcal group A conjugate vaccine has virtually eliminated meningococcal group A, epidemics due to non-group A meningococcal and other meningeal pathogens continue to occur [15]. In Ghana, pneumococcal meningitis is still common despite introduction of PCV13 into the routine infant immunization program, predominantly due to meningitis caused by serotype 1 [16].
Streptococcus suis is an emerging zoonosis that causes meningitis in Asia and has been linked to exposure to pigs [17]. It is the most frequent cause of bacterial meningitis in adults in southern Vietnam and has caused outbreaks in China.
Mortality — Despite the decreased mortality of meningitis with the advent of effective antibiotics, mortality from meningitis still remains significant. The global burden of disease study in 2016 documented that meningitis caused 318,000 deaths and 21,866,000 disability-adjusted life years annually in the world [18].
The use of adjunctive dexamethasone in pneumococcal meningitis has been shown in clinical trials to decrease mortality in high-income countries [19]. One Dutch study and two studies based in the United States have shown reductions in mortality after the Infectious Diseases Society of America guidelines recommended adjunctive dexamethasone for adults with bacterial meningitis in 2004 [2,6,20]. The use of adjunctive dexamethasone therapy in S. pneumoniae meningitis is discussed in detail elsewhere. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
HEALTH CARE-ASSOCIATED VENTRICULITIS AND MENINGITIS — Meningitis may also be associated with a variety of invasive procedures or head trauma. This has often been classified as nosocomial meningitis because a different spectrum of microorganisms (ie, gram-negative bacilli and staphylococci) is more likely to be implicated than that associated with community-acquired meningitis. These patients often present with clinical symptoms during hospitalization or after hospital discharge, so the term health care-associated ventriculitis and meningitis (HCAVM) is preferred [21]. HCAVM is primarily a disease of neurosurgical patients with specific risk factors for the development of meningitis, including craniotomy, placement of ventricular or lumbar catheters, head trauma, and, very rarely, lumbar punctures [21]. (See 'Risk factors' below.)
The distribution of causative organisms is appreciably different in health care-associated meningitis compared with community-acquired meningitis. Aerobic gram-negative bacilli, such as Escherichia coli and Klebsiella species, are rare causes of community-acquired meningitis in adults but are a common cause of health care-associated infections, mostly following neurosurgical procedures [21,22]. In a study of 215 adult and pediatric patients with HCAVM as per the 2015 United States Centers for Disease Control and Prevention definition, 106 (49 percent) cases had a positive cerebrospinal fluid (CSF) culture, which was caused by gram-positive bacteria (eg, Staphylococcus, Streptococcus, etc) in two-thirds and due to gram-negative organisms (eg, Pseudomonas, Enterobacteriaceae, etc) in one-third of cases [23]. In contrast, the majority of meningitis cases that occur after basilar skull fracture or early after otorhinologic surgery care are caused by microorganisms that colonize the nasopharynx, especially S. pneumoniae [21].
The majority of patients with HCAVM have adverse clinical outcomes, and HCAVM is an independent poor prognostic factor in neurosurgical patients with intracranial hemorrhages [24]. Among patients with health care-associated meningitis, patients with gram-negative meningitis are sicker than those with gram-positive infections, with lower Glasgow Coma Scale scores, lower CSF glucose, higher CSF lactate, and higher proportion of mechanical ventilation, although there is no difference in clinical outcomes at discharge [25].
Prevention of HCAVM is of the utmost importance and can be achieved by perioperative prophylactic antimicrobial therapy, implementation of a standardized protocol for inserting CSF shunts and drains, and by use of antimicrobial-impregnated shunts or drains [24]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery'.)
RISK FACTORS — In both community-acquired and health care-associated meningitis, the organism responsible for acute bacterial meningitis depends in part upon the route of acquisition and underlying host factors (table 1). There are three major mechanisms for developing meningitis:
●Colonization of the nasopharynx, with subsequent bloodstream invasion followed by central nervous system (CNS) invasion.
●Invasion of the CNS following bacteremia due to a localized source, such as infective endocarditis.
●Direct entry of organisms into the CNS from a contiguous infection (eg, sinuses, mastoid), trauma, neurosurgery, a cerebrospinal fluid (CSF) leak, or medical devices (eg, CSF shunts, intracerebral pressure monitors, or, in children, cochlear implants with positioners) [26-28]. (See "Infections of cerebrospinal fluid shunts and other devices" and "Cochlear implant infections".)
The importance of these factors in adults with health care-associated meningitis can be illustrated by the following findings:
●In a report of 197 cases of nosocomial meningitis, the major risk factors, which accounted for 75 percent of cases, were neurosurgery or head trauma within the past month, a neurosurgical device, or a CSF leak [26].
●In a review of 95 cases of post-craniotomy meningitis, independent risk factors for meningitis were CSF leak (present in 37 percent, adjusted odds ratio 28.4) and wound infection (present in 45 percent, adjusted odds ratio 3.7) [27]. In another study of patients who underwent 334 craniotomies, meningitis was encountered in 16 procedures; in a multivariate analysis, the risk for meningitis was independently associated with perioperative glucocorticoid use, CSF leak, and ventricular drainage [29].
Risk factors for recurrent bacterial meningitis are similar to risk factors for initial episodes and include anatomic defects of the spinal cord, brain or inner ear, acquired defects due basilar skull fractures or surgery, parameningeal infections, or immunodeficiency [30]. (See "Approach to the adult with recurrent infections", section on 'Meningitis'.)
Host factors that can predispose to meningitis include asplenia, complement deficiency, glucocorticoid excess, diabetes mellitus, alcoholism, hypogammaglobulinemia, and HIV infection (table 2). Patients with suspected meningitis should also be questioned for other predisposing factors, such as:
●Recent infection (especially respiratory or ear infection)
●Recent exposure to someone with meningitis
●Injection drug use
●Recent head trauma
●Otorrhea or rhinorrhea
●Recent travel (eg, Hajj pilgrimage) [31]
The frequency of underlying host risk factors in patients with bacterial meningitis was illustrated in the series of 1412 patients in the Netherlands [9]. Almost one-half had a predisposing condition such as otitis or sinusitis (34 percent), pneumonia (9 percent), or an immunocompromised state (11 percent).
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Bacterial meningitis (The Basics)")
SUMMARY
●In the pre-antibiotic era bacterial meningitis was virtually 100 percent fatal. Despite the effectiveness of current antibiotics in clearing bacteria from the cerebrospinal fluid (CSF), bacterial meningitis continues to cause significant morbidity and mortality worldwide. (See 'Introduction' above.)
●In the United States, following the institution of routine infant immunization with the conjugate Haemophilus influenzae type b vaccine in 1990 and the 7-valent Streptococcus pneumoniae (pneumococcus) conjugate vaccine in 2000 (PCV7) followed by the 13-valent pneumococcal vaccine (PCV13) in 2010, bacterial meningitis has decreased in frequency, and the peak incidence of bacterial meningitis has shifted from children under five years of age to adults (figure 1). (See 'Community-acquired meningitis' above.)
●S. pneumoniae remains the leading pathogen of community-acquired bacterial meningitis globally and continues to be associated with a high mortality rate. (See 'Global' above.)
●Large epidemics of meningitis due to serogroup A Neisseria meningitidis in sub-Saharan Africa have been eliminated by mass vaccination using the meningococcal A conjugate vaccine, but epidemics due to non-group A meningococcal and other meningeal pathogens continue to occur.(See 'Global' above.)
●Streptococcus suis is an emerging zoonosis that causes meningitis in Asia and has been linked to exposure to pigs or pork. (See 'Global' above.)
●Despite the decreased mortality of meningitis with the advent of effective antibiotics, mortality from meningitis still remains significant. The use of adjunctive dexamethasone in pneumococcal meningitis has been shown in clinical trials and observational studies to decrease mortality in high-income countries. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
●Health care-associated ventriculitis and meningitis are primarily diseases of neurosurgical patients. The most common pathogens are gram-positive bacteria (eg, Staphylococcus, Streptococcus, etc) and gram-negative organisms (eg, Pseudomonas, Enterobacteriaceae, etc). Specific risk factors for the development of health care-associated meningitis include craniotomy, placement of ventricular or lumbar catheters, CSF leak, and head trauma. (See 'Health care-associated ventriculitis and meningitis' above.)
●The organism responsible for acute bacterial meningitis depends in part upon the route of acquisition and underlying host factors (table 1). There are three major mechanisms for developing meningitis:
•Colonization of the nasopharynx, with subsequent bloodstream invasion followed by central nervous system (CNS) invasion
•Invasion of the CNS following bacteremia due to a localized source, such as infective endocarditis
•Direct entry of organisms into the CNS from a contiguous infection (eg, sinuses, mastoid), trauma, neurosurgery, a CSF leak, or medical devices (eg, CSF shunts, intracerebral pressure monitors, or, in children, cochlear implants with positioners) (see 'Risk factors' above)
