Pneumococcal meningitis …

Ravindra Kumar Garg DM FRCP

Infectious Disorders

Updated 09.03.2024
Released 05.02.2005
Expires For CME 09.03.2027

Pneumococcal meningitis

Author: Ravindra Kumar Garg DM FRCP

See Contributor Disclosures

Editor: Christina M Marra MD

Pneumococcal meningitis

In This Article

Quick Link

Introduction

Overview

Streptococcus pneumoniae is the leading cause of bacterial meningitis in adults in the United States and accounts for significant morbidity and mortality in essentially all age groups. Prompt recognition and treatment can improve outcomes. Treatment guidelines recommend that dexamethasone should be added to initial empiric antibiotic therapy. A low-dose dexamethasone protocol significantly reduced mortality in pneumococcal meningitis patients. In this article, the author reviews the clinical manifestations of S pneumoniae infection, with an emphasis on neurologic symptoms and key features that can help avoid pitfalls leading to missed or late diagnosis. Cerebral vasculitis is a significant complication observed in approximately one-third of patients with pneumococcal meningitis. The lockdown and COVID-19 containment measures had a favorable impact on the transmission of life-threatening invasive diseases caused by S pneumoniae, H influenzae, and N meningitidis globally. The reported incidence of S pneumoniae infections decreased by 68% at 4 weeks and 82% at 8 weeks after start of the lockdown. Current diagnostic laboratory techniques are evaluated, and up-to-date treatment recommendations based on the most recent research and expert opinions are incorporated. Research regarding the importance of endocarditis and bacteremia to neuropathogenesis, as well as the effect of bacterial meningitis on neurogenesis, is presented.

Key points

	• Globally, community-acquired bacterial meningitis is most frequently caused by Streptococcus pneumoniae.
	• Patients with a basilar skull or cribriform fracture with a CSF leak are at increased risk of acquiring pneumococcal meningitis.
	• CSF infection with Streptococcus pneumoniae often leads to a severe degree of meningeal inflammation.
	• Pneumococcal meningitis is treated intravenously with a combination of a third-generation cephalosporin and vancomycin.
	• Dexamethasone reduces mortality.
	• Dexamethasone treatment leads to lower rates of hearing loss.

Historical note and terminology

In 1881, Streptococcus pneumoniae was identified simultaneously by Pasteur in France, who named it Microbe septice mique du salive, and by Sternberg in the United States, who called it Micrococcus pasteuri. By the late 1880s, the term pneumococcus had come into general use because of the association between this organism and lobar pneumonia. In 1926, the term Diplococcus was assigned because of the organism’s appearance in gram-stained sputum. Finally, in 1974, the organism was renamed, Streptococcus pneumoniae because of its morphology during growth in liquid medium (104; 65).

Clinical manifestations

Presentation and course

Streptococcus pneumoniae infections are more common in children and persons over 65 years of age. S pneumoniae is a causative agent for many serious systemic infections, including pneumonia, septicemia, sinusitis, and otitis media (21; 58). The most frequent predisposing and associated conditions for pneumococcal meningitis are pneumonia, sinusitis, or otitis media. Invasive pneumococcal disease is defined as a culture of S pneumoniae from a normally sterile body site (blood or cerebrospinal fluid but not sputum) (16).

Pneumococcal meningitis symptoms typically include fever, headache, nausea, vomiting, irritability, and lethargy proceeding to further clouding of consciousness. Fever may be 103°F or higher. Clinical signs include evidence of meningeal irritation, though this can be lacking in children, the elderly, and the deeply comatose. Focal signs may also appear. The course is frequently fulminant, with rapid neurologic deterioration leading to respiratory arrest and death (24; 99).

Lobar pneumonia and meningitis are the two most serious forms of S pneumoniae infection. Lobar pneumonia affects more people and, therefore, causes more morbidity and mortality, whereas meningitis has a higher mortality rate. S pneumoniae is the most common cause of bacterial meningitis in adults worldwide. In people over the age of 16, Streptococcus pneumoniae is responsible for approximately 72% of bacterial meningitis cases, whereas Neisseria meningitidis accounts for around 11%. In early-onset neonatal meningitis, Escherichia coli and Streptococcus agalactiae together make up about 35% of cases (65; 39). S pneumoniae is also a frequent cause of recurrent bacterial meningitis in individuals with a dural defect.

Finally, as a respiratory pathogen, the most typical coexisting complications will affect the upper or lower airways. Concomitant pneumonia is frequent in patients with S pneumoniae meningitis. Not infrequently, it is possible to obtain a history of productive cough, dyspnea, and constitutional symptoms in the days prior to onset of meningitis-like symptoms. Bacteria and inflammatory exudate accumulate in the alveoli of the lung, allowing a diagnosis of pneumonia to be made when a consolidated area appears on chest x-ray (65). The more severe cases of pneumonia are more likely to be accompanied by bacteremia (70; 103) and, therefore, with meningitis. Meningitis occurs in approximately 8% of patients who become bacteremic with this organism (80).

S pneumoniae is a common etiologic agent of otitis media in both children and adults (85; 29) and is either the first or second leading cause of acute sinusitis (38). In a study of 2548 episodes of community-acquired bacterial meningitis, otitis was present in 27% of cases, with Streptococcus pneumoniae identified as the primary pathogen in 88% of these cases (78). Otitis was associated with a favorable outcome (odds ratio 0.74), but ear surgery showed no significant impact on patient outcomes. These infections can provide a source of meningitis by either hematogenous spread or direct extension. It is reasonable to perform an otologic examination on any patient presenting with fever and altered consciousness (71).

The triad of pneumococcal pneumonia, meningitis, and endocarditis is a rare but serious condition known as Austrian syndrome (46). Alcoholism is the most common predisposing factor, but it is also seen with intravenous drug use (08), and the diagnosis of endocarditis should be considered early in every patient with pneumococcal meningitis or bacteremia (57).

Other complications of S pneumoniae include septic arthritis and osteomyelitis (33), both of which are manifestations of bacteremic spread, as is meningitis. Osteomyelitis also tends to involve the vertebral bones (98) and, from there, can extend directly into the central nervous system.

Prognosis and complications

The prognosis of Streptococcus pneumoniae meningitis, as with most bacterial meningitis, relates directly to early diagnosis and prompt initiation of appropriate antibiotic therapy (07). Streptococcus pneumoniae was the leading cause of meningitis-related deaths in 2019, accounting for 18.1% of all meningitis deaths (34). Morbidity, however, is high, even with the best possible treatment, and significant, permanent neurologic sequelae are observed in up to a third of the survivors (62; 07; 88). After pneumococcal meningitis, adult patients are at greater risk of neurologic and neuropsychologic deficits, impaired daily activities, and poor quality of life (49).

French data for children (5 to 15 years) with a diagnosis of pneumococcal meningitis between 2001 and 2013 were analyzed. Among the 316 children with pneumococcal meningitis, the mortality rate was approximately 10%, and additionally, 23% of cases had severe complications (abscess, coma, hemodynamic failure, cerebral thrombophlebitis, or deafness) (40). In an American retrospective study, in-patient data from 2008 to 2014 were evaluated. During the study period, there were 10,493 hospitalizations due to pneumococcal meningitis. Data collected involved patients from all age groups (children younger than 2 years of age to over 65 years of age). There were 1016 deaths, with case fatality rate ranging from 8.3% to 11.2% (45).

Acute neurologic complications, especially coma, are associated with later behavioral and developmental difficulties, developmental delay, hearing loss, motor defects, and seizures (76). Independent predictors of a poor outcome include low Glasgow coma scale score, presence of a cranial nerve palsy, elevated sedimentation rate (105), advanced age, presence of an underlying chronic illness, presence of associated pneumonia, absence of associated otitis media, seizures, requirement for assisted ventilation, high CSF protein concentration, low CSF glucose concentration, CSF white count below 500 cells/microliter (72; 52), abnormal deep tendon reflexes, presence of stroke or hydrocephalus on imaging, and delay in antibiotic administration (88).

Complications during acute illness are similar to those seen with meningitides of any etiology and include subdural effusion, empyema, ischemic or hemorrhagic stroke, cerebritis, ventriculitis, abscess, and hydrocephalus (37; 65). Hearing loss is the most common long-term neurologic sequela of pneumococcal meningitis, occurring in up to 35% of pediatric survivors (52). The pneumococcal toxin pneumolysin is an important factor involved in ototoxic toxicity (75). Other focal neurologic deficits, such as ataxia and paresis, occur in an additional 16% (72).

Cerebral vasculitis is a significant complication observed in approximately 29% of patients with pneumococcal meningitis as per a retrospective study conducted across two tertiary hospitals from 2002 to 2020. The study found that cerebral vasculitis was likely to occur when there was a delay in hospital admission after the first symptoms, with an increased risk noted for those having high CRP levels at admission and those who took NSAIDs before hospitalization. Furthermore, elevated CSF protein levels were also identified as a risk factor for cerebral vasculitis. Interestingly, the administration of dexamethasone showed no influence on the occurrence of cerebral vasculitis in patients with pneumococcal meningitis (06).

Inflammation of the meninges can spread to involve the blood vessels, leading to a type of vasculopathy known as delayed cerebral vasculopathy. Delayed cerebral vasculopathy associated with dexamethasone use is a slower, less immediate condition affecting the cerebral arteries. Boix-Palop and colleagues noted delayed cerebral vasculopathy in approximately 10% of patients with pneumococcal meningitis (09). Delayed cerebral vasculopathy was considered if these patients had clinical worsening or if they failed to show an expected improvement after beginning antibiotic treatment. Neuroimaging in these patients showed small or large cerebral vessel disease. The patients who had delayed cerebral vasculopathy were severely ill, had a longer duration of illness, and more frequently had unfavorable outcomes. The authors hypothesized that the abrupt withdrawal of corticosteroids led to a cascade of rebound inflammatory changes manifesting as vasculopathy.

Cognitive impairment, particularly psychomotor slowing, is found in approximately 30% of survivors and is stable on formal testing over time after meningitis, despite subjective perception of improvements over time (43). Another study assessed the long-term neurologic, cognitive, and quality-of-life outcomes in adults who survived pneumococcal meningitis (49). The study found that even 1 to 5 years after the acute illness, 34% of patients exhibited persistent neurologic issues, predominantly hearing loss. Cognitive impairments were also significant, affecting domains like alertness and cognitive flexibility. The study also reported that these survivors had considerably lower quality-of-life scores compared to a control group.

Clinical vignette

A 45-year-old man with alcoholism was brought by ambulance from a homeless shelter to an emergency room due to alteration in mental status. A few hours earlier, he had told the staff at the shelter that he had a bad headache. He had also vomited once. He then went to rest on his bunk. When staff checked on him, they found him to be confused. In the emergency room, he was noted to have a temperature of 39.1 degrees Celsius. He responded to his first name but was not oriented to place or time. He was given doses of ceftriaxone, vancomycin, and ampicillin. A head CT was unremarkable, and a lumbar puncture was performed. CSF examination demonstrated an opening pressure of 500 mmHg, a white count of 4914 cells/ul with 91% neutrophils, a glucose concentration of 5 mg/dl, and a protein concentration of 279 mg/dl. Gram stain revealed gram positive diplococci, and a presumptive diagnosis of pneumococcal meningitis was made.

The patient was admitted to the neurologic intensive care unit. Triple antibiotic coverage was continued pending definitive speciation and antibiotic sensitivity determination. Intravenous dexamethasone was also added to the regimen. The patient’s condition continued to deteriorate, and he required ventilatory support. A repeat head CT demonstrated worsening cerebral edema. The patient developed signs of cerebral herniation. He was temporarily stabilized, but then required pressor support. He became increasingly bradycardic, and eventually died, 30 hours after initial presentation.

CSF and blood cultures both confirmed the diagnosis of infection with Streptococcus pneumoniae, sensitive to all tested antibiotics.

Biological basis

Etiology and pathogenesis

Streptococcus pneumoniae are the prototypic extracellular bacterial pathogens. In the absence of anticapsular antibody, they resist phagocytosis and grow extracellularly. They are gram-positive cocci that tend to grow in chains. They are catalase negative and grow better with a source of catalase, such as red blood cells. S pneumoniae produce pneumolysin, which degrades hemoglobin to a green pigment; they are, therefore, surrounded by a green zone on blood-agar growth media, a process termed alpha-hemolysis. Currently, at least 100 distinct serotypes have been identified based on the structure and antigenicity of their polysaccharide capsules. Of these, a limited number of capsular serotypes account for most invasive pneumococcal diseases (65; 102; 18). Invasive disease caused by different serotypes may result in different degrees of host response (84), leading to different pathogenic mechanisms, clinical courses, and outcomes. Certain serotypes are more frequently associated with pneumococcal meningitis. For instance, among children, serotype 15B/C is more frequently linked to meningitis. Among adults, serotype 12F is more frequent in cases of meningitis. Notably, serotype 15B/C also presents with issues of antibiotic resistance, particularly against penicillin and macrolides (64).

Streptococcus pneumoniae causes infection of the upper and lower respiratory tracts by spread from the nasopharynx, which is normally colonized; it causes infection elsewhere, including the central nervous system, via hematogenous spread. In fact, an autopsy study of children who died from bacterial meningitis showed no evidence for direct extension, suggesting that even in cases of otitis media, meningitis may be due to bacteremia (30). The bacteremia may actually contribute to the neurologic injury by affecting cerebral blood flow regulation, blood-brain barrier permeability, and cerebral edema (10; 74).

A key bacterial factor enabling S pneumoniae to cause disease is its capsular polysaccharide. The capsule allows the organism to escape immune surveillance and ingestion by phagocytes. The capsule may have electrochemical forces that repel phagocytes and may mask cell wall constituents, which would otherwise be immunogenic (65). Pneumococcal bacterial genetic variation is a determinant of invasive pneumococcal disease phenotype. Variations in S pneumoniae genome also contribute to determining the clinical phenotype of invasive pneumococcal disease. For example, the presence of pneumococcal gene slaA along with sequence cluster 9 were independent predictors of meningitis. In addition, presence of a set of four pneumococcal genes co-located on a prophage independently predicted 30-day increased mortality (23).

Various bacterial and host factors contribute to pathogenicity of the organism within the central nervous system. In its attempt to fight the infection, the host inflammatory response probably causes most of the pathological damage.

The processes by which Streptococcus pneumoniae bacteria move from the bloodstream to cross the blood-brain barrier and infect the brain are not completely clear. Once S pneumoniae enters the central nervous system, bacteria multiply in the CSF. Subsequently, there is bacterial lysis with a release of toxic material in the CSF. The prominent toxic materials released during bacterial lysis include the pneumolysin protein, bacterial wall fragments, and capsular components. These toxic materials orchestrate an intense inflammatory reaction in the CSF and brain parenchyma (92; 44). Pneumolysin produced by Streptococcus pneumoniae activates the complement system, causing inflammation. Simultaneously, it interferes with complement effectiveness by binding to complement proteins or damaging host cells, reducing immune clearance. This dual action allows the bacterium to evade the immune system, promoting infection and bacterial survival within the host. By interfering with complement activation, pneumolysin helps the bacteria evade host defenses, allowing for increased survival and propagation within the host (25). Furthermore, pneumolysin destroys phagocytic cells, activates complement and other cytokines, and induces apoptosis-like programmed cell death in neurons and brain-derived endothelial cells (59; 82). In addition, an altered balance of matrix metalloproteinase (MMP-9) and its tissue inhibitor (TIMP-1) may play a role in disruption of the blood-brain barrier and extent of cortical damage in a rat model of pneumococcal meningitis (86). Upregulation of aquaporin-4 may contribute to increased water permeability across the blood-brain barrier, accounting for the brain edema seen in pneumococcal meningitis (73).

In response to bacterial infection of the central nervous system, neural progenitor cells proliferate and differentiate, although bacterial factors, like cell wall constituents, may trigger immunoreactivity, which can hamper this neurogenesis. Immunoreactivity refers to the immune system's response to foreign antigens (41). Work in a murine model of pneumococcal meningitis has demonstrated upregulated expression of brain derived neurotrophic factor (BDNF) and its receptor (TrkB), which is associated with increased density of dentate granule cells in the hippocampal formation (94). BDNF was demonstrated to have in vitro neuroprotective effects in bacterial meningitis (55).

Brain histopathology of 31 patients who died of pneumococcal meningitis was assessed. Common pathological observations were inflammation of medium-large arteries, cerebral hemorrhage, cerebritis, arterial and venous thrombosis, infarction, and ventriculitis. Inflammation of arteries leading to obstruction of the vascular lumen was associated with cerebral infarction (32). Deliran and colleagues performed brain autopsy in two patients who died of pneumococcal meningitis and had clinical cerebral venous thrombosis (28). They noted multifocal deep intramural inflammation in the cerebral venous sinus. Bacteria were identified within the intramural inflammation and thrombus. Similar changes were not noted in patients with cerebral venous thrombosis without meningitis and in patients with uncomplicated bacterial meningitis. Delayed cerebral thrombosis in pneumococcal meningitis arises from multiple factors like vascular inflammation, large artery thromboembolism, and infectious aneurysms, often exacerbated by lingering inflammation (31).

Epidemiology

Streptococcus pneumoniae is the leading cause of bacterial meningitis in the United States and in other parts of world. Infants and young children are particularly vulnerable for Streptococcus pneumoniae meningitis. In an American retrospective study from 2008 to 2014 there were 10,493 hospitalizations due to pneumococcal meningitis. Overall, pneumococcal meningitis incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease). Among children less than 2 years of age, the average annualized pneumococcal meningitis rate decreased by 45% from 2.19 to 1.20 per 100,000. Annual pneumococcal meningitis rates decreased in those 18 to 39 years of age (0.25 to 0.15 cases per 100,000) and 40 to 64 years of age (0.95 to 0.54 cases per 100,000) (45).

In 2019, S pneumoniae was the leading cause of meningitis-related deaths globally, accounting for 18.1% of all-age fatalities. N meningitidis (13.6%) and K pneumoniae (12.2%) followed closely. Among children under 5, S pneumoniae was responsible for 17.3% of meningitis deaths (34).

Between 2012 and 2019 in England, a study collected 6554 laboratory-confirmed cases of bacterial meningitis, with an annual incidence of 1.49 per 100,000. The primary pathogens were Streptococcus pneumoniae (19.9%), Neisseria meningitidis (12.2%), and Staphylococcus aureus (11.5%). Interestingly, while pneumococcal meningitis showed an increasing trend, meningococcal and group A streptococcal meningitis declined. Infants under 3 months had the highest incidence due to group B streptococci, whereas children aged 3 to 11 months mainly had pneumococcal and meningococcal infections. The overall 30-day fatality rate was 10%, but group A streptococcal meningitis had a staggering 55.3% mortality rate. Healthcare, antibiotic resistance, public health strategies, and microbial differences explain variations (91).

Patients with various underlying conditions, such as asplenic states, cancer, alcoholism, malnutrition, diabetes mellitus, HIV, and other chronic diseases, may be at increased risk for developing pneumococcal infection, including meningitis (35; 36; 03). Certain ethnic groups, including Native Americans, Alaskans, and Australian Aboriginals, may have an incidence as much as 10-fold greater than the general population (26; 96; 47). The reasons for this remain unclear. Infants (but not neonates) up to 2 years of age and adults over 65 years are also at increased risk (11).

Transmission can occur due to close contact, such as in daycare centers, military camps, prisons, homeless shelters, and nursing homes (63; 42; 66; 87). The lockdown and COVID-19 containment measures had a favorable impact on the transmission of life-threatening invasive diseases caused by S pneumoniae, H influenzae, and N meningitidis globally. The reported incidence of S pneumoniae infections decreased by 68% at 4 weeks and 82% at 8 weeks after start of the lockdown (March 2020) (12).

Prevention

The Centers for Disease Control and Prevention recommends routine pneumococcal vaccine for the following types of patients: immunocompetent but at increased risk of acquiring pneumococcal infection or having a serious complication, such as patients with chronic pulmonary disease, cardiovascular disease, diabetes, alcoholism, liver and renal disease, CSF leak, cochlear implants, and those older than 65 years of age or younger than 2 years of age; and immunocompromised patients, including those with functional or anatomic asplenia (including sickle cell disease), congenital or acquired immunodeficiency, malignancy, leukemia or lymphoma, HIV infection, or organ transplantation. Vaccine may also be reasonable for other populations at risk by virtue of ethnicity (Native Americans) or crowded living conditions (65; 14).

Pneumococcal conjugate vaccines are now part of national immunization programs of many countries (21). There are two types of pneumococcal vaccines currently available: pneumococcal conjugate vaccine (PCV13), which consists of purified capsular polysaccharides from 13 bacterial serotypes, and pneumococcal polysaccharide vaccine (PPSV23), which consists of purified capsular polysaccharides from the 23 serotypes responsible for 90% of invasive pneumococcal infections. The polysaccharides are conjugated to a carrier protein, which makes them more immunogenic and effective in protecting against infection, particularly in young children less than 2 years of age. Furthermore, the vaccine protects against both systemic and mucosal infection and prevents nasopharyngeal colonization, thereby reducing transmission in the community.

The Advisory Committee on Immunization Practices (ACIP) under the CDC has updated its recommendations for pneumococcal vaccinations in U.S. In the U.S., two pneumococcal vaccines, pneumococcal conjugate (PCV13, PCV15, or PCV20) and pneumococcal polysaccharide (PPSV23), are used to protect against pneumococcal disease. They offer substantial but not complete protection against various pneumococcal bacteria types. The CDC recommends these vaccines especially for at-risk groups. All children under 5 should receive PCV13 or PCV15. Those aged 5 to 18 with specific medical conditions should also get PCV13 or PCV15, and those between 2 to 18 with certain conditions need PPSV23. Adults aged 65 and above or those 19 to 64 with particular medical conditions or risk factors should receive PCV15 or PCV20, with PCV15 followed by PPSV23. Those who had earlier vaccinations like PCV13 or PCV7 should consult with their healthcare provider about completing their series. Moreover, adults aged 65 or older who previously took PCV13 (but not PCV15 or PCV20) and PPSV23 after turning 65 can discuss with their doctor the option of receiving PCV20 (19).

For adults aged 65 years and older or those aged 19 to 64 with certain medical conditions or risk factors, the ACIP recommends either a single dose of PCV20 alone or PCV15 in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Those who began their vaccination series with the earlier 13-valent vaccine (PCV13) but haven’t received all recommended PPSV23 doses can opt for a single dose of PCV20 or one or more doses of PPSV23. For those who have received PPSV23 but not PCV, the new CDC guidance recommends either PCV15 or PCV20. A single supplemental dose of PCV13 is advised for children 14 to 59 months old who completed a PCV7 schedule. Those with medical conditions such as chronic heart, lung, and liver disease; diabetes; immunocompromised; asplenia; or alcoholism should get this up to the age of 71 months. It's applicable even if they've had the PPSV23 vaccine. It is important to wait 8 weeks before administering a subsequent pneumococcal vaccine dose after the last dose of PCV7 or PPSV23 (15; 19). Both types of vaccines are well tolerated and highly effective, and they can be administered at the same time as other vaccines (04).

Differential diagnosis

Confusing conditions

The history and examination data obtained from any given case of acute bacterial meningitis can be quite variable. Some findings are typically present, whereas others may be absent. Additionally, the signs and symptoms frequently seen with acute bacterial meningitis, including fever, behavioral or personality changes, and mental status changes can be nonspecific and suggest other diagnoses, including systemic infection or sepsis, viral encephalitis or meningitis, fungal or tuberculous meningitis, trauma or closed head injury, multiple metabolic abnormalities (hypoglycemia, ketoacidosis, electrolyte imbalance, uremia, toxic exposure), seizure, and brain tumor. Even meningismus does not exclude alternative diagnoses such as subarachnoid hemorrhage, intracranial hemorrhage, and epidural abscess. In order to prevent morbidity and mortality from missed diagnoses, it is important to keep a high index of suspicion for acute bacterial meningitis and err on the side of starting treatment early and potentially unnecessarily (07).

Streptococcus pneumoniae and Neisseria meningitidis are the most common etiologic agents of bacterial meningitis after 1 year of age. In children less than 1 year of age, Group B streptococci and gram-negative enteric bacilli, particularly Escherichia coli, are the leading etiologic agents, presumably because of exposure to these agents during birth. Due to passive transfer of maternal antibodies, these neonates do not typically develop Haemophilus influenzae or pneumococcal or meningococcal meningitis (69).

In the setting of a preceding sinusitis, otitis media, head trauma, neurosurgical procedure, or cerebrospinal fluid leak, S pneumoniae and nontypeable H influenzae are both common etiologic agents of recurrent meningitis (48; 01) because both are a common part of “normal” skin and nasopharyngeal colonization. One study provides good evidence that surgical repair of CSF leaks effectively prevents recurrent bacterial meningitis (90).

In patients over 50 years of age, the most common causes of bacterial meningitis include S pneumoniae, Listeria monocytogenes, and gram-negative bacilli (79; 51). H influenzae is included in the gram-negative group, along with E coli, Enterobacter, and Pseudomonas. S pneumoniae is more likely in association with pneumonia, Pseudomonas in association with chronic lung disease, E coli, or Enterobacter in the setting of urinary tract infection, and S pneumoniae or H influenzae in the setting of sinusitis, otitis media, head trauma, or a neurosurgical procedure. Listeria monocytogenes can also be seen, especially in the immunosuppressed elderly, and Staphylococcus aureus is seen with dural disruption.

Diagnostic workup

Bacterial meningitis, including that caused by Streptococcus pneumoniae, should be considered and promptly treated in any patient with a compatible presentation, keeping in mind that the presentation may be atypical in some patients, especially young children and the elderly. Neutrophilic CSF pleocytosis and a decreased CSF glucose concentration are strongly suggestive of bacterial meningitis (07). Empiric therapy is initiated with a third- or fourth-generation cephalosporin and vancomycin along with dexamethasone (22).

A minority of patients with bacterial meningitis, particularly with pneumococcal meningitis, have normal CSF leukocyte counts. This finding is more common in individuals who are immunocompromised and is associated with a poor outcome (101).

Imaging is recommended before lumbar puncture in meningitis if there are signs of raised intracranial pressure, focal neurologic deficits, altered consciousness, recent seizures, or immunocompromised status, to prevent herniation risks. Images should be looked for contraindications for lumbar puncture. In such a scenario, empirical treatment should be initiated before the patient is sent for neuroimaging (22).

With S pneumoniae meningitis, as well as most other etiologic agents, both blood and CSF cultures will usually be positive if they are collected before administration of antibiotics. However, again, treatment should be initiated without delay. Multiplex PCR platforms for simultaneous detection of multiple bacterial pathogens causing meningitis are now commercially available. A probe to detect unique S pneumoniae RNA sequences is also available. Methods for detecting antibody to capsular polysaccharide have proven neither sensitive nor specific enough to be clinically useful.

Rapid antigen tests show promise for quick pneumococcal meningitis diagnosis. A systematic review and meta-analysis were undertaken to assess the effectiveness of rapid antigen tests in CSF for pneumococcal meningitis detection. After reviewing various databases, 44 studies involving 14,791 participants were included. These studies evaluated the rapid antigen tests' sensitivity and specificity against CSF culture. Results indicated a high sensitivity (99.5%) and specificity (98.2%) for the rapid tests. With a 4.2% median prevalence, the tests had positive and negative predictive values of 70.8% and 100%, respectively (89).

Historically, pneumococci have been identified in culture by the following characteristics: alpha-hemolysis of blood agar, catalase negativity, susceptibility to optochin, and solubility in bile salts (65). With the modern techniques of molecular biology, reliance on these bacterial properties may be less important, but cultures remain vital to determine antibiotic sensitivity.

Management

When bacterial meningitis is suspected, emergent antibiotic treatment must be initiated without waiting for speciation (07). In persons older than the neonatal period, empiric treatment is directed primarily against S pneumoniae and N meningitidis. Current recommendations for treatment of community-acquired meningitis for ages 3 months to 50 years is vancomycin 15 mg/kg IV every 8 to 12 hours and up to 2 g/day (maintain serum trough concentration of 15 to 20 ug/ml) plus either cefotaxime 50 mg/kg IV every 4 to 6 hours (maximum 2 g IV every 4 hours) or ceftriaxone 50 to 100 mg/kg IV every 12 hours (maximum 2 g IV every 12 hours). For patients over age 50 years, addition of ampicillin 2 g IV every 4 hours is recommended (97; 61; 99).

In adults, dexamethasone should ideally be added to empirical therapy before or at the same time as the first antibiotic dose, and it should be continued for 4 days in those with proven pneumococcal meningitis (106). The dose is 0.15 mg/kg every 6 hours (27; 97; 100). The European Society of Clinical Microbiology and Infectious Diseases guidelines suggest that corticosteroids can still be started up to 4 hours after commencement of antibiotic treatment (99). The UK guidelines recommend that for adults, dexamethasone can be given up to 12 hours after antibiotics are started (61). There has been some concern that dexamethasone could decrease the penetration of vancomycin into the CSF. However, a study demonstrated that appropriate levels of vancomycin are reached in the CSF of patients with pneumococcal meningitis receiving dexamethasone as long as proper serum levels of vancomycin are maintained (81). Dexamethasone 0.15 mg/kg every 6 hours, initiated prior to the first dose of antibiotic and continued for the first 2 to 4 days of treatment, decreases the risk of neurologic sequelae from community-acquired bacterial meningitis in children (54; 67; 93).

A 31-year retrospective study (1977 to 2018) on 363 cases of pneumococcal meningitis revealed that a low-dose dexamethasone protocol (12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose), combined with mannitol and phenytoin, significantly reduced mortality. Patients treated with dexamethasone had lower overall mortality (11.6% vs. 35%), early mortality (5.8% vs. 24%), and neurologic mortality (7.4% vs. 23%) compared to those without dexamethasone, highlighting its potential benefit in improving outcomes (13).

Current recommendations advocate for the immediate admission of pneumococcal meningitis patients to ICUs. A study of 4052 adults in France with pneumococcal meningitis and sepsis, conducted between 2011 and 2020, compared direct ICU admission with secondary ICU admission. Findings revealed that direct ICU admission significantly reduced mortality, even after adjusting for disease severity and other factors, preventing one death for every 11 patients directly admitted to the ICU (95).

In addition to medication therapies, it is imperative that appropriate supportive care be instituted. Advancements in intensive care techniques offer significant benefit for patients with bacterial meningitis, including S pneumoniae meningitis.

Outcomes

Pneumococcal meningitis has always been associated with a high possibility of mortality and morbidity in adults. Authors from the Netherlands analyzed data between October 1998 and April 2002 and between January 2006 and July 2018. The outcome of pneumococcal meningitis in adults was better in the latter era of administration of conjugate vaccines and adjunctive dexamethasone compared to the former era, when these two interventions were used less. Nonetheless, in a cohort of 1783 patients (1816 pneumococcal meningitis episodes), there were 363 episodes of in-hospital death (20%). Unfavorable outcomes were recorded in 772 episodes (43%). Delayed cerebral venous thrombosis occurred in 29 patients (2%), and more half of these died (50). Neurofunctional disability in adults is frequent 1 year after community-acquired bacterial meningitis, particularly following pneumococcal meningitis. In a cohort of 281 patients at 12 months, 84 (30%) patients had neuro-functional disability and six patients died. Dexamethasone did not impact the likelihood of neurofunctional disability (02).

The cerebrospinal fluid (CSF) bacterial load has been identified as a key indicator of worse outcomes in adults with pneumococcal meningitis. A study involving 152 patients revealed a median CSF bacterial load of 1.6 × 10⁴ DNA copies/mL. Higher bacterial loads were linked to severe complications such as circulatory shock and cerebrovascular issues, along with increased risk of unfavorable outcomes (OR: 2.8) and mortality (OR: 3.1) (20).

A pediatric observational study analyzed 505 cases of Streptococcus pneumoniae meningitis across three continents (60). Compared to other causes, this type of meningitis had double the mortality rate (33%) and triple the rate of poor outcomes (15%). Key predictors of poor outcomes included a Glasgow Coma Score below 13, age under 1 year, seizures, and prior parenteral antibiotic use. Outcomes were particularly severe in Angola.

References

01: Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J. Community-acquired recurrent bacterial meningitis in adults. Clin Infect Dis 2007;45(5):e46-51. PMID 17682979
02: Akroum S, Tubiana S, de Broucker T, et al. Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis. Infection 2022;50(5):1363-72. PMID 35657529
03: Albrich WC, Baughman W, Schmotzer B, Farley MM. Changing characteristics of invasive pneumococcal disease in Metropolitan Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate vaccine. Clin Infect Dis 2007;44(12):1569-76. PMID 17516400
04: American Academy of Pediatrics. Pneumococcal infections. In: Pickering LK, editor. Red Book: 2006 Report of the Committee on Infectious Diseases, 27th edition. Elk Grove Village: American Academy of Pediatrics, 2006:525-37.
05: American College of Obstetricians and Gynecologists. Maternal immunization practice advisory October 2022. Accessed September 2023. Available at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/10/maternal-immunization. 2022.
06: Artiaga A, Herman F, Arquizan C, et al. Cerebral vasculitis as a complication of pneumococcal meningitis: a cohort study. Infect Dis Now 2023;53(8):104772. PMID 37619963
07: Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 2006;34:2758-65. PMID 16915106
08: Beadsworth MB, Wooton D, Chenzbraun A, Beeching NJ. Austrian’s syndrome: The first described case of pneumococcal meningitis pneumonia and endocarditis in an injecting drug user. Eur J Intern Med 2007;18:605-6. PMID 18054715
09: Boix-Palop L, Fernández T, Pelegrín I, et al. Delayed cerebral vasculopathy in pneumococcal meningitis: epidemiology and clinical outcome. A cohort study. Int J Infect Dis 2020;97:283-9. PMID 32531430
10: Brandt CT, Holm D, Liptrot M, et al. Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis. J Infect Dis 2008;197(2):235-44. PMID 18173365
11: Breiman RF, Spika JS, Navarro VJ, Darden PM, Darby CP. Pneumococcal bacteremia in Charleston County, South Carolina: a decade later. Arch Intern Med 1990;150:1401-5. PMID 2369239
12: Brueggemann AB, Jansen van Rensburg MJ, Shaw D, et al. Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data. Lancet Digit Health 2021;3(6):e360-70. PMID 34045002
13: Cabellos C, Guillem L, Pelegrin I, et al. A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis. Infect Dis (Lond) 2024;56(11):974-82. PMID 38922314
14: Centers for Disease Control and Prevention. Pneumococcal vaccination: summary of who and when to vaccinate. Accessed June 2021a.
15: Centers for Disease Control and Prevention. Pneumococcal vaccine recommendations. Accessed June 2021b.
16: Centers for Disease Control and Prevention. Invasive Pneumococcal Disease (IPD) (Streptococcus pneumoniae) 2017 Case Definition. CSTE Position Statement(s), 16-ID-08. Available at: https://wwwn.cdc.gov/nndss/conditions/invasive-pneumococcal-disease/case-definition/2017/. Accessed November 2017.
17: Centers for Disease Control and Prevention. Guidelines for vaccinating pregnant women. Available at: https://www.cdc.gov/vaccines/pregnancy/hcp-toolkit/guidelines.html#ppsv23. Accessed May 2019.
18: Centers for Disease Control and Prevention. Pneumococcal disease; for laboratorians. Available at: https://www.cdc.gov/pneumococcal/laboratorians.html#:~:text=There%20are%20more%20than%20100,vaccines%20against%20this%20global%20pathogen. Accessed September 19, 2023a.
19: Centers for Disease Control and Prevention. Pneumococcal vaccination. Available at: https://www.cdc.gov/pneumococcal/vaccination.html. Accessed September 10, 2023b.
20: Chekrouni N, van Soest TM, da Cruz Campos AC, Brouwer MC, van de Beek D. Bacterial load in cerebrospinal fluid predicts unfavourable outcome in pneumococcal meningitis: a prospective nationwide cohort study. Clin Microbiol Infect 2024;30(6):772-8. PMID 38479702
21: Corcoran M, Vickers I, Mereckiene J, et al. The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd effect? Epidemiol Infect 2017;145(11):2390-9. PMID 28712384
22: Costerus JM, Brouwer MC, Sprengers MES, Roosendaal SD, van der Ende A, van de Beek D. Cranial computed tomography, lumbar puncture, and clinical deterioration in bacterial meningitis: a nationwide cohort study. Clin Infect Dis 2018;67(6):920-6. PMID 29522090
23: Cremers AJH, Mobegi FM, van der Gaast-de Jongh C, et al. The contribution of genetic variation of Streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease. Clin Infect Dis 2019;68(1):61-9. PMID 29788414
24: Curtis S, Stobart K, Vandermeer B, Simel DL, Klassen T. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatrics 2010;126(5):952-60. PMID 20974781
25: Dao TH, Rosch JW. JMM profile: Streptococcus pneumoniae: sugar-coated captain of the men of death. J Med Microbiol 2021;70(11):001446. PMID 34779760
26: Davidson M, Parkinson AJ, Bulkow LR, Fitzgerald MA, Peters HV, Parks DJ. The epidemiology of invasive pneumococcal disease in Alaska, 1986-1990: ethnic differences and opportunities for prevention. J Infect Dis 1994;170:368-76. PMID 8035023
27: de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549-56. PMID 12432041
28: Deliran SS, Engelen-Lee JY, Brouwer MC, van de Beek D. Cerebral venous thrombosis in pneumococcal meningitis: an autopsy study. Clin Neuropathol 2021;40(3):126-33. PMID 33433314
29: Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance. Pediatr Infect Dis J 1999;18:1-9. PMID 9951971
30: Eavey RD, Gao Y, Schuknecht HF, Pineda MG. Otologic features of bacterial meningitis of childhood. J Pediatr 1985;136:2025-9. PMID 3973777
31: Engelen-Lee JY, Brouwer MC, Aronica E, van de Beek D. Delayed cerebral thrombosis complicating pneumococcal meningitis: an autopsy study. Ann Intensive Care 2018;8(1):20. PMID 29427117
32: Engelen-Lee JY, Brouwer MC, Aronica E, van de Beek D. Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path). Acta Neuropathol Commun 2016;4:26. PMID 27001057
33: Forestier E, Sordet C, Solal JC, et al. Bone and joint infection due to Streptococcus pneumoniae in two immunocompetent adults. Joint Bone Spine 2006;73:325-8. PMID 16495104
34: GBD 2019 Meningitis Antimicrobial Resistance Collaborators. Global, regional, and national burden of meningitis and its aetiologies, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2023;22(8):685-711. PMID 37479374
35: Geiseler PJ, Nelson KE, Levin S, Reddi KT, Moses VK. Community acquired purulent meningitis: a review of 1316 cases during the antibiotic era, 1954-1976. Rev Infect Dis 1980;2:725-45. PMID 6763303
36: Godeau B, Bachir D, Schaeffer A, et al. Severe pneumococcal sepsis and meningitis in human immunodeficiency virus infected adults with sickle cell disease. Clin Infect Dis 1992;15:327-9. PMID 1520768
37: Grigoriadis E, Gold WL. Pyogenic brain abscess caused by Streptococcus pneumoniae: Case report and review. Clin Infect Dis 1997;25:1108-12. PMID 9402366
38: Gwaltney JM, Scheld WM, Sande MA, Sydnor A. The microbial etiology and antimicrobial therapy of adults with acute community acquired sinusitis: a fifteen year experience at the University of Virginia and review of other selected studies. J Allergy Clin Immunol 1992;90:457-62. PMID 1527337
39: Hasbun R. Progress and challenges in bacterial meningitis: a review. JAMA 2022;328(21):2147-54. PMID 36472590
40: Hénaff F, Levy C, Cohen R, et al. Risk factors in children older than 5 years with pneumococcal meningitis: data from a National Network. Pediatr Infect Dis J 2017;36(5):457-61. PMID 28403047
41: Hoffmann O, Mahrhofer C, Rueter N, et al. Pneumococcal cell wall induced meningitis impairs adult hippocampal neurogenesis. Infect Immun 2007;75(9):4289-97. PMID 17591796
42: Hoge CW, Reichler MR, Dominguez EA, et al. An epidemic of pneumococcal disease in an overcrowded, inadequately ventilated jail. N Engl J Med 1994;331:643-8. PMID 8052273
43: Hoogman M, van de Beek D, Weisfelt M, de Gans J, Schmand B. Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry 2007;78(10):1092-6. PMID 17353256
44: Hupp S, Förtsch C, Graber F, Mitchell TJ, Iliev AI. Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis. Nat Commun 2022;13(1):5032. PMID 36028511
45: Jacobs DM, Yung F, Hart E, Nguyen MNH, Shaver A. Trends in pneumococcal meningitis hospitalizations following the introduction of the 13-valent pneumococcal conjugate vaccine in the United States. Vaccine 2017;35(45):6160-5. PMID 28951086
46: Juanatey CG, Testa A, Mayo J, Gay MAG. Austrian syndrome: report of two new cases and literature review. Int J Cardiol 2006;108:273-5. PMID 16139379
47: King BA, Richmond P. Pneumococcal meningitis in Western Australian children: epidemiology, microbiology, and outcome. J Paediatr Child Health 2004;40:611-5. PMID 15469529
48: Kline MW. Review of recurrent bacterial meningitis. Pediatr Infect Dis J 1989;8:630-4. PMID 2677957
49: Kloek AT, Brouwer MC, Schmand B, Tanck MWT, van de Beek D. Long-term neurologic and cognitive outcome and quality of life in adults after pneumococcal meningitis. Clin Microbiol Infect 2020;26(10):1361-7. PMID 32006689
50: Koelman DLH, Brouwer MC, Ter Horst L, van der Ende A, van de Beek D. Pneumococcal meningitis in adults: a prospective nationwide cohort study over a 20-year period. Clin Infect Dis 2022;74(4):657-67. PMID 34036322
51: Koelman DLH, van Kassel MN, Bijlsma MW, Brouwer MC, van de Beek D, van der Ende A. Changing epidemiology of bacterial meningitis since introduction of conjugate vaccines: three decades of national meningitis surveillance in The Netherlands. Clin Infect Dis 2021;73(5):e1099-107. PMID 33247582
52: Kutz JW, Simon LM, Chennupati SK, Giannoni CM, Manolidis S. Clinical predictors for hearing loss in children with bacterial meningitis. Arch Otolaryngol Head Neck Surg 2006;132(9):941-5. PMID 16982970
53: Landrum LM, Hawkins A, Goodman JR. Pneumococcal meningitis during pregnancy: a case report and review of the literature. Infect Dis Obstet Gynecol 2007;2007:63624. PMID 17485820
54: Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis: results of two double blind, placebo controlled trials. N Engl J Med 1988;319:964-71. PMID 3047581
55: Li L, Shui QX, Liang K, Ren H. Brain derived neurotrophic factor rescues neurons from bacterial meningitis. Pediatr Neurol 2007;36(5):324-9. PMID 17509465
56: Liechti FD, Bijlsma MW, Brouwer MC, van de Beek D. Effect of the COVID-19 pandemic on clinical characteristics and outcomes of adult pneumococcal meningitis patients - a Dutch prospective nationwide cohort study. Infection 2024;52(5):1657-62. PMID 38831205
57: Luzzati R, Pinamonti B, Giacomazzi D, Sinagra G, Zingone B. Aortic-right atrium fistula complicating Austrian Syndrome: a case report and literature review. Infez Med 2007;15(2):124-8. PMID 17599001
58: Manoharan A, Manchanda V, Balasubramanian S, et al. Invasive pneumococcal disease in children aged younger than 5 years in India: a surveillance study. Lancet Infect Dis 2017;17(3):305-12. PMID 27956163
59: Marriott HM, Dockrell DH. Streptococcus pneumoniae: the role of apoptosis in host defense and pathogenesis. Int J Biochem Cell Biol 2006;38(11):1848-54. PMID 16844403
60: Mbakwe PL, Roine I, Cruzeiro ML, Kallio M, Peltola H, Pelkonen T. Clinical picture and risk factors for poor outcome in Streptococcus pneumoniae meningitis of childhood on three continents. Pediatr Infect Dis J 2024;43(5):415-9. PMID 38359336
61: McGill F, Heyderman RS, Michael BD, et al. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect 2016;72(4):405-38. PMID 26845731
62: McIntyre PB, Macintyre CR, Gilmour R, Wang H. A population based study of the impact of corticosteroid therapy and delayed diagnosis on the outcome of childhood pneumococcal meningitis. Arch Dis Child 2005;90:391-6. PMID 15781931
63: Mercat A, Nguyen J, Dautzenberg B. An outbreak of pneumococcal pneumonia in two men’s shelters. Chest 1991;99:147-51. PMID 1984946
64: Meroc E, Fletcher MA, Hanquet G, et al. Systematic literature review of the epidemiological characteristics of pneumococcal disease caused by the additional serotypes covered by the 20-valent pneumococcal conjugate vaccine. Microorganisms 2023;11(7):1816. PMID 37512988
65: Musher DM. Streptococcus pneumoniae. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia: Churchill Livingstone, 2000:2128-44.
66: Nuorti JP, Butler JC, Crutcher JM, et al. An outbreak of multidrug resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents. N Engl J Med 1998;338:1861-8. PMID 9637804
67: Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991;324:1525-31. PMID 2027357
68: Oligbu G, Collins S, Djennad A, et al. Effect of pneumococcal conjugate vaccines on pneumococcal meningitis, England and Wales, July 1, 2000-June 30, 2016. Emerg Infect Dis 2019;25(9):1708-18. PMID 31441745
69: Oordt-Speets AM, Bolijn R, van Hoorn RC, Bhavsar A, Kyaw MH. Global etiology of bacterial meningitis: a systematic review and meta-analysis. PLoS One 2018;13(6):e0198772. PMID 29889859
70: Ort S, Ryan RL, Barden G, D’Esopo N. Pneumococcal pneumonia in hospitalized patients: clinical and radiological presentations. JAMA 1983;249:214-8. PMID 6848806
71: Ostergaard C, Hoiby N, Konradsen HB, Samuelsson S. Prehospital diagnostic and therapeutic management of otogenic Streptococcus pneumoniae meningitis. Scand J Infect Dis 2006;38:172-80. PMID 16507498
72: Ostergaard C, Konradsen HB, Samuelsson S. Clinical presentation and prognostic factors of Streptoccocus pneumoniae meningitis according to the focus of infection. BMC Infect Dis 2005;5:93. PMID 16253143
73: Papadopoulos MC, Verkman AS. Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. J Biol Chem 2005;280:13906-12. PMID 15695511
74: Pedersen M, Brandt CT, Knudsen GM, et al. The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats. J Cereb Blood Flow Metab 2008;28(1):126-34. PMID 17565362
75: Perny M, Solyga M, Grandgirard D, Roccio M, Leib SL, Senn P. Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures. Hear Res 2017;350:100-9. PMID 28460251
76: Pikis A, Kavaliotis J, Tsikoulas J, Andrianopoulos P, Venzon D, Manios S. Long-term sequelae of pneumococcal meningitis in children. Clin Pediatr (Phila) 1996;35:72-8. PMID 8775479
77: Quiambao BP, Nohynek HM, Kayhty H, et al. Immunogenicity and reactogenicity of 23-valent pneumococcal polysaccharide vaccine among pregnant Filipino women and placental transfer of antibodies. Vaccine 2007;25(22):4470-7. PMID 17442467
78: Ranzenigo M, van Soest TM, Hensen EF, et al. Otitis in patients with community-acquired bacterial meningitis: a nationwide prospective cohort study. Clin Infect Dis 2024;79(2):329-35. PMID 38655694
79: Rasmussen HH, Sorensen HT, Moller-Petersen J, Mortensen FV, Nielsen B. Bacterial meningitis in elderly patients: clinical picture and course. Age Ageing 1992;21:216-20. PMID 1615786
80: Raz R, Elhanan G, Shimoni Z, et al. Pneumococcal bacteremia in hospitalized Israeli adults: epidemiology and resistance to penicillin. Clin Infect Dis 1997;24:1164-8. PMID 9195076
81: Ricard JD, Wolff M, Lacherade JC, et al. Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study. Clin Infect Dis 2007;449(2):250-5. PMID 17173226
82: Rupprecht TA, Angele B, Klein M, et al. Complement C1q and C3 are critical for the innate immune response to Streptococcus pneumoniae in the central nervous system. J Immunol 2007;178:1861-9. PMID 17237437
83: Sáez-Llorens X, McCracken GH Jr. Bacterial meningitis in children. Lancet 2003;361(9375):2139-48. PMID 12826449
84: Sandgren A, Albiger B, Orihuela CJ, Tuomanen E, Normark S, Normark BH. Virulence in mice of pneumococcal clonal types with known invasive disease potential in humans. J Infect Dis 2005;192:791-800. PMID 16088828
85: Schwartz LE, Brown RB. Purulent otitis media in adults. Arch Intern Med 1992;152:2301-4. PMID 1444690
86: Sellner J, Leib SL. In bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP9/TIMP1 ratio and increased collagen type IV degradation. Neurobiol Dis 2006;21:647-56. PMID 16257222
87: Siedler A, Reinert RR, Toschke M, Al-Lahham A, von Kries R. Regional differences in epidemiology of invasive pneumococcal disease in toddlers in Germany. Pediatr Infect Dis J 2005;24:1114-5. PMID 16371880
88: Singhi P, Bansal A, Geeta P, Singhi S. Predictors of long term neurological outcome in bacterial meningitis. Indian J Pediatr 2007;74(4):369-74. PMID 17476082
89: Someko H, Okazaki Y, Tsujimoto Y, Ishikane M, Kubo K, Kakehashi T. Diagnostic accuracy of rapid antigen tests in cerebrospinal fluid for pneumococcal meningitis: a systematic review and meta-analysis. Clin Microbiol Infect 2023;29(3):310-9. PMID 36503113
90: Sprekelsen MB, Alobid I, Mullol J, Trobat F, Barberan MT. Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis. Rhinology 2005;43:277-81. PMID 16405272
91: Subbarao S, Ribeiro S, Campbell H, Okike I, Ramsay ME, Ladhani SN. Trends in laboratory-confirmed bacterial meningitis (2012-2019): national observational study, England. Lancet Reg Health Eur 2023;32:100692. PMID 37538400
92: Subramanian K, Henriques-Normark B, Normark S. Emerging concepts in the pathogenesis of the Streptococcus pneumoniae: from nasopharyngeal colonizer to intracellular pathogen. Cell Microbiol 2019;21(11):e13077. PMID 31251447
93: Syrogiannopoulos GA, Lourida AN, Theodoridou MC, et al. Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen. J Infect Dis 1994;169:853-8. PMID 8133101
94: Tauber SC, Stadelmann C, Spreer A, Bruck W, Nau R, Gerber J. Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis. J Neuropathol Exp Neurol 2005;64:806-15. PMID 16141791
95: Thy M, Dupuis C, Mageau A, Mourvillier B, et al. Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database. Ann Intensive Care 2024;14(1):15. PMID 38279066
96: Torzillo PJ, Hanna JN, Morey F, Gratten M, Dixon J, Erlich J. Invasive pneumococcal disease in central Australia. Med J Aust 1995;162:182-6. PMID 7877538
97: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39(9):1267-84. PMID 15494903
98: Turner DP, Weston VC, Ispahani P. Streptococcus pneumoniae spinal infection in Nottingham, United Kingdom: not a rare event. Clin Infect Dis 1999;28:873-81. PMID 10825053
99: van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016;22 Suppl 3:S37-62. PMID 27062097
100: van de Beek D, de Gans J, McIntyre P, Prasad K. Steroids in adults with acute bacterial meningitis: a systematic review. Lancet Infect Dis 2004;4:139-43. PMID 14998499
101: van Soest TM, Chekrouni N, van Sorge NM, Brouwer MC, van de Beek D. Bacterial meningitis presenting with a normal cerebrospinal fluid leukocyte count. J Infect 2022;84(5):615-20. PMID 35245581
102: Vieira AC, Gomes MC, Rolo Filho M, Eudes Filho J, Bello EJ, de Figueiredo RB. Streptococcus pneumoniae: a study of strains isolated from cerebrospinal fluid. J Pediatr (Rio J) 2007;83(1):71-8. PMID 17279283
103: Watanakunakorn C, Bailey TA. Adult bacteremic pneumococcal pneumonia in a community teaching hospital, 1992-1996: a detailed analysis of 108 cases. Arch Intern Med 1997;157:1965-71. PMID 9308508
104: Watson DA, Musher DM, Jacobson JW. A brief history of the pneumococcus in biomedical research: a panoply of discovery. Clin Infect Dis 1993;17:913-24. PMID 8286641
105: Weisfelt M, van de Beek D, Spanjaard L, Reitsma JB, de Gans J. Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series. Lancet Neurol 2006;5:123-9. PMID 16426988
106: Young N, Thomas M. Meningitis in adults: diagnosis and management. Intern Med J 2018;48(11):1294-1307. PMID 30387309

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Ravindra Kumar Garg DM FRCP

Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.
See Profile

Editor

Christina M Marra MD

Dr. Marra of the University of Washington School of Medicine has no relevant financial relationships to disclose.
See Profile

Former Authors

Jeffrey A Rumbaugh MD

Patient Profile

Age range of presentation: 1 month to 65+ years
Sex preponderance: male:female, 1:1
Heredity: none
Population groups selectively affected: Eskimo, Native American Indian, Australian Aboriginal
Occupation groups selectively affected: child care center personnel

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Pneumococcal meningitis

Associated Disorders

Austrian syndrome
Bacterial meningitis
Endocarditis
Osteomyelitis
Otitis media
- Pleural empyema
- Pneumonia
- Septic arthritis
- Sinusitis

Differential Diagnosis

encephalitis
systemic infection
sepsis
viral encephalitis
viral meningitis
- fungal meningitis
- tuberculous meningitis
- trauma
- closed head injury
- child abuse
- hypoglycemia
- ketoacidosis
- electrolyte imbalance
- uremia
- toxic exposure
- seizure
- brain tumor
- subarachnoid hemorrhage
- intracranial hemorrhage
- epidural abscess
- Haemophilus influenzae
- Neisseria meningitidis
- Group B streptococci
- gram-negative enteric bacilli
- Escherichia coli
- Enterobacter
- Pseudomonas
- Listeria monocytogenes
- Staphylococcus aureus

Also Relevant

Blood-brain barrier
Gram-negative bacillary meningitis
Haemophilus influenzae meningitis
Headache associated with intracranial infection
Infective endocarditis
- Meningococcal meningitis
- Neurologic complications of vaccination
- Recurrent meningitis

Pneumococcal meningitis …

Pneumococcal meningitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Prion diseases

Rabies

Malaria

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Neurocysticercosis

Trichinosis

Zika virus: neurologic complications

Pneumococcal meningitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Prion diseases

Rabies

Malaria

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Neurocysticercosis

Trichinosis

Zika virus: neurologic complications

This is an article preview.
Start a Free Account
to access the full version.