Streptococcal Meningitis

Etiology

Numerous Streptococcus species are capable of causing meningitis. Among them, S pneumoniae is the most clinically significant and is considered the leading etiological agent of bacterial meningitis globally, affecting both adults and children. Within the beta-hemolytic group, S agalactiae (group B streptococcus [GBS]) is particularly notable, representing the most common cause of bacterial meningitis in neonates and young infants. Other streptococcal species, such as those belonging to the Streptococcal viridans group or group A streptococcus, are less frequently implicated but can occasionally act as causative agents of meningitis in both pediatric and adult populations. 

Epidemiology

The etiologic agents responsible for streptococcal meningitis vary significantly by age group. S pneumoniae remains the most common cause of bacterial meningitis in children older than 1 month and adults across all ages. In individuals older than 16, S pneumoniae accounts for approximately 72% of bacterial meningitis cases.[1] In pediatric populations, the prevalence of pneumococcal meningitis ranges geographically, from 22.5% in Europe to 41.1% in Africa.[2] 

In the developing world, invasive pneumococcal disease (IPD) constitutes a significant public health concern, contributing to substantial morbidity and mortality. IPD is estimated to cause up to 1 million deaths annually among children younger than 5.[3] The case-fatality rate for pneumococcal meningitis in children varies widely, ranging from approximately 12% in high-income countries to as high as 61% in low-income settings.[4] 

The introduction of pneumococcal conjugate vaccines has led to a significant decline in the incidence of pneumococcal meningitis. In the United States (US), the prevalence of pneumococcal meningitis decreased from 0.8 per 100,000 population in 1997 to 0.3 per 100,000 in 2010, following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000.[5] Similarly, in Japan, a substantial reduction in incidence was observed, with a 53.6% decrease following the introduction of PCV7 and a further 70.2% decrease after transitioning to the 13-valent conjugate vaccine (PCV13), particularly among children aged 3 years or younger.[6] 

In neonates, S agalactiae (GBS) is a leading causative pathogen responsible for meningitis.[7] In the US, between 2006 and 2015, the incidence of early-onset disease, defined as symptom onset within the first 6 days of life, declined from 0.37 to 0.23 per 1000 live births, primarily due to the implementation of intrapartum antibiotic prophylaxis. However, the incidence of late-onset disease remained stable during this period.[8] Globally, the incidence of invasive GBS disease in infants is approximately 0.49 per 1000 live births, with the highest burden observed in Africa.[9] Other streptococcal groups infrequently cause meningitis. S viridans accounts for an estimated 0.3% to 3.0% of adult bacterial meningitis cases, and approximately 1% of cases in children.[10] Additionally, group A streptococcal meningitis has been diagnosed in adults in around 2% of community-acquired bacterial meningitis cases.[11]

Pathophysiology

Meningitis occurs when bacteria access the central nervous system by entering the bloodstream, crossing the blood-brain barrier, or spreading directly to the meninges from adjacent structures such as the skin or nasal cavity. The most common initial site of infection is the nasopharynx, which may be colonized by S pneumoniae capable of evading host immune defenses. During IPD, the pathogen enters the bloodstream, triggering activation of the complement and coagulation cascades. This systemic immune response leads to the release of large quantities of inflammatory mediators, increasing the blood-brain barrier's permeability and facilitating bacterial penetration into the subarachnoid space. The resulting inflammation underlies the hallmark features of bacterial meningitis, including significant CSF pleocytosis.

History and Physical

Symptoms of bacterial meningitis, including those caused by streptococcal species, may develop abruptly (more commonly) or gradually over several days. Clinical manifestations typically appear within 3 to 7 days following exposure. However, no pathognomonic signs or symptoms reliably distinguish the specific causative pathogen based solely on patient history and physical examination.

Adults

The classic triad of diagnostic symptoms of meningitis in adults— fever, nuchal rigidity, and altered mental status—is present in only 44% of adults with bacterial meningitis.[12] However, nearly all patients exhibit at least 2 of the following 4 symptoms: headache, fever, neck stiffness, and altered mental status.[12] Additional commonly reported complaints include severe headache exacerbated by head movement, nausea, vomiting, and photophobia.

A study by Lucht evaluated the diagnostic accuracy of clinical examination for meningitis in adults, revealing that the sensitivity of individual symptoms such as headache, vomiting, or fever was less than 30%. In comparison, nuchal rigidity had a sensitivity of 45%.[13] Notably, the study demonstrated that the absence of 2 or more signs—headache, fever, altered mental status, or neck stiffness—makes the diagnosis of meningitis highly unlikely, with a negative predictive value of 95%. Results from a Danish study focusing on adults with pneumococcal meningitis found that fever and altered mental status were present in nearly all patients upon admission. Other symptoms, such as back rigidity, headache, and seizures, were observed less frequently, reported in 57%, 41%, and 11% of cases, respectively.[14]

On physical examination, signs of meningeal irritation, such as nuchal rigidity, Kernig sign, and Brudzinski sign, may be present. While these signs demonstrate high specificity for meningitis, their sensitivity is low. Results from a study conducted by Thomas et al, which evaluated adults with suspected meningitis, reported that the specificity of both Kernig's and Brudzinski's signs was 95%, while their sensitivity was only 5%. Nuchal rigidity demonstrated a sensitivity of 30% and specificity of 68%.[15] Altered mental status is another common clinical finding and may manifest as confusion, decreased level of consciousness, or sometimes seizures. The jolt accentuation test elicited by rapid horizontal rotation of the head is considered to have the highest sensitivity among physical exam findings; however, its specificity remains limited. 

Pediatrics

Clinical signs of neonatal and infant meningitis are often nonspecific, including irritability or lethargy, fever or hypothermia, poor feeding, vomiting, and diarrhea. These early symptoms are subtle and can easily be attributed to other neonatal or pediatric conditions. More specific clinical findings, such as bulging fontanel, nuchal rigidity, and seizures, are typically late manifestations of the disease in this age group.[16]

In a study by Amarilyo et al, approximately 50% of neonates with meningitis and an open fontanelle presented with a bulging fontanelle.[17] The study enrolled children aged 2 months to 16 years with suspected meningitis and found that Kernig and Brudzinski signs had sensitivities of 27% and 51%, respectively, but demonstrated high positive predictive values of 77% and 81%. Further, classic meningeal signs are frequently absent in infants younger than 6 months. According to a study by Weber et al, several clinical variables were independently associated with meningitis in children aged 2 months to 3 years.[18] These included poor feeding, appearing severely ill, lethargy or unconsciousness, neck stiffness, and a bulging fontanelle. These findings highlight the importance of maintaining a high index of suspicion and relying on a combination of clinical observations when evaluating young children or possible meningitis.

Evaluation

The cornerstone of meningitis diagnosis, including streptococcal meningitis, is CSF examination; this is essential not only for confirming the diagnosis but also for identifying the causative pathogen, which allows for subsequent de-escalation of antimicrobial therapy. CSF should be obtained promptly once bacterial meningitis is suspected, unless there are specific contraindications to performing an immediate lumbar puncture (LP). These contraindications include the risk of cerebral herniation, severe uncorrected coagulopathy, or the presence of a critical clinical condition requiring stabilization.

According to the Infectious Diseases Society of America (IDSA) guidelines, a cranial computed tomography (CT) scan should be performed before LP in patients with focal neurological deficits (excluding isolated facial palsy), altered level of consciousness, papilledema, recent seizure activity (within 1 week of presentation), a history of central nervous system disease, or immunocompromised status. During LP, CSF samples are collected and analyzed for physical and chemical properties, cell count, Gram stain, latex agglutination test (LAT), culture, and, if available, polymerase chain reaction (PCR). In streptococcal meningitis, CSF typically demonstrates neutrophilic pleocytosis (white blood count ≥500/µL), an elevated lactate level, and a decreased CSF-to-serum glucose ratio. Specific CSF parameters have prognostic significance. For instance, a leukocyte count less than 50/mm^3 and an elevated CSF protein level (≥660 mg/dL) have been associated with poor outcomes in children with pneumococcal meningitis.[19]

Gram staining of CSF provides rapid, though sometimes limited, preliminary identification of bacteria. The LAT is a rapid diagnostic tool that detects capsular antigens of several pathogens, including S pneumoniae, and often yields results faster than culture. Although CSF culture remains the gold standard for confirming the causative pathogen, its sensitivity may be limited. Results from a comparative study found that fewer than half of bacterial meningitis cases yielded positive culture results, particularly when patients had received prior antibiotic therapy.[20]

PCR has emerged as a valuable diagnostic adjunct, particularly in cases where culture results are negative due to prior use of antimicrobials. However, its utility is limited to the bacterial species in the assay's primer mix. In the same study, LAT demonstrated greater sensitivity than traditional Gram staining and culture in detecting specific organisms such as Haemophilus influenzae, S pneumoniae, and GBS. Nevertheless, the combined use of Gram stain, culture, and LAT was superior to any single method alone in establishing the etiological diagnosis.[20]

Additional laboratory tests include blood culture, which is essential for increasing the likelihood of identifying the causative pathogen, particularly in cases where CSF cultures are negative. Other supportive tests typically include a complete blood count, inflammatory markers (which are often markedly elevated), coagulation profiles, and assessments of renal and hepatic function. Despite the need for diagnostic evaluation, these procedures should not delay the initiation of empiric antimicrobial therapy, as early treatment is crucial for improving clinical outcomes in bacterial meningitis. 

Treatment / Management

Streptococcal meningitis requires the immediate initiation of antibiotic therapy, as any delay in treatment is associated with significantly increased morbidity and mortality and is therefore unacceptable.

S pneumoniae

Initial empiric treatment for pneumococcal meningitis typically includes a combination of vancomycin and a third-generation cephalosporin, such as cefotaxime or ceftriaxone. According to the 2025 World Health Organization (WHO) guidelines and 2024 National Institute for Health and Care Excellence (NICE) recommendations, monotherapy with a third-generation cephalosporin is generally sufficient in most clinical settings.[21] However, in regions with a high prevalence of S pneumoniae strains resistant to cephalosporins, empirical addition of vancomycin is advised to ensure adequate antimicrobial coverage.  

Once antimicrobial susceptibility results become available, therapy should be de-escalated accordingly. Switching to penicillin G or ampicillin is appropriate in cases where the isolate is penicillin-susceptible. For patients with a documented history of anaphylaxis to β-lactam antibiotics, chloramphenicol may serve as an alternative agent. Adjunctive therapy with dexamethasone is recommended in pneumococcal meningitis. Evidence from multiple studies has demonstrated that dexamethasone significantly reduces mortality and the incidence of unfavorable outcomes when compared to antibiotic therapy alone.[22][23](A1)

S agalactiae

Monotherapy with penicillin G or ampicillin is appropriate for treating meningitis caused by GBS. Current evidence does not support the use of adjunctive corticosteroid therapy in this context. Available data indicate that dexamethasone does not confer a survival benefit, nor does it reduce the incidence of severe complications in GBS meningitis. Therefore, its use is neither recommended nor routinely practiced in clinical settings.[7]

S viridans, Group A Streptococcus

Penicillin G remains an effective treatment for meningitis caused by S viridans or group A Streptococcus. Supportive care constitutes an essential management component and includes appropriate fluid resuscitation, measures to reduce intracranial pressure, administering antipyretics, and providing analgesics to manage fever and discomfort. 

Prevention

Among all streptococcal meningitis cases, only pneumococcal meningitis is preventable by vaccination. Two vaccine types exist against S pneumoniae: the older pneumococcal polysaccharide (PPSV23) and the newer pneumococcal conjugate vaccines (PCVs). PPSV23 includes 23 pneumococcal capsular polysaccharides, offering the broadest serotype coverage. However, it is ineffective in children younger than 2 due to their immature immune response, making it suitable only for individuals 2 years and older.

A meta-analysis by Sikjær reported vaccine effectiveness (VE) against vaccine-type invasive pneumococcal disease (VT-IPD) ranging from 28% to 54.1% in individuals aged 65 to 79, and 7.5% to 34% in those aged 80 to 85 or older.[24] Results from a Danish study showed that the VE of PPSV23 in adults 65 and older was 32% against all-type IPD and 41% against PPSV23-serotype IPD.[25](A1)

PCVs consist of pneumococcal capsular polysaccharides linked to a carrier protein and are immunogenic in infants. These vaccines are recommended for routine pediatric immunization. Five types exist: PCV10, PCV13, PCV15, PCV20, and PCV21, though only PCV10 through PCV20 are currently approved for children.

In a US study, receiving 3 or more doses of PCV13 in children younger than 5 was 90.2% effective against VT-IPD. VE for specific serotypes among children receiving 3 or greater doses was 86.8% for serotype 19A, 50.2% for serotype 3, and 93.8% for serotype 19F.[26] In adults aged 65 and older, PCV13 demonstrated a VE of 61.5% against PCV13-serotype IPD.[27] Randomized controlled trials suggest that PCV15 has immunogenicity and safety comparable to PCV13.[28]

A German cost-effectiveness analysis estimated that PCV20, when administered instead of PCV15, would prevent an additional 11,334 IPD cases and 41,596 deaths in the pediatric population, owing to its broader serotype coverage.[29] As of June 27, 2024, the Advisory Committee on Immunization Practices has recommended PCV21 for adults 19 and older who are currently recommended to receive a dose of PCV. PCV21 includes 8 additional serotypes not found in other approved vaccines.(B3)

Meningitis caused by GBS is also preventable through maternal screening and the use of intrapartum antibiotic prophylaxis. All pregnant women should be screened for GBS colonization via vaginal and rectal swabs between 36 0/7 and 37 6/7 weeks of gestation; those testing positive should receive intrapartum antibiotic prophylaxis to prevent transmission to the newborn.

Global maternal colonization rates range from 11% to 35% [30], with about 50% of colonized mothers passing the bacteria to their infants during labor or after membrane rupture.[31] Up to 2% of exposed newborns would develop EOD without antibiotic prophylaxis.[31] In the US, GBS EOD incidence has declined from 1.8 per 1000 live births in 1992 to 0.2 per 1000 in 2020, largely due to the widespread implementation of this strategy.[32] (A1)

Differential Diagnosis

The differential diagnosis of streptococcal meningitis encompasses a range of other CNS infections. Meningitis caused by different bacterial etiology (such as Neisseria meningitidis) can present with similar clinical features and may be indistinguishable from streptococcal meningitis based solely on symptomatology. Therefore, CSF culture remains essential for accurate etiological identification.

Viral and fungal meningitides must also be considered and systematically ruled out. Encephalitis, which may present with overlapping clinical signs, should be distinguished from meningitis by the presence of parenchymal brain involvement, as evidenced by neuroimaging or altered neurological function. Additionally, other potential causes of altered mental status or coma, such as cerebrovascular accidents, toxic or metabolic encephalopathies, hypoglycemia, and significant electrolyte disturbances, should be excluded during diagnostic evaluation.

• Brain abscess
• Brain tumors
• Subdural and epidural abscess
• CNS leukemia
• Hypersensitivity to drugs
• CNS tuberculosis
• Disorders associated with vasculitis (eg, Kawasaki disease and collagen vascular disease)
• Lead and other encephalopathies
• Encephalitis
• Cerebrovascular accident
• Hypoglycemia
• Intoxication
• Viral meningitis
• Fungal meningitis

Prognosis

The prognosis of streptococcal meningitis remains serious and often uncertain. Results from a Danish study focusing on pneumococcal meningitis showed that the overall case-fatality rate was 21%, with adults exhibiting a 10-fold higher mortality rate than in children.[14] Causes of death included neurological complications such as brain herniation and cerebrovascular complications (reported in 41% of patients), and systemic causes such as septic shock and multiple-organ dysfunction, accounting for nearly a quarter of deaths. Other causes were responsible for 8% of fatalities, while approximately one-third of patients died due to a combination of systemic and neurological complications.[14]

Several prognostic factors were identified as being associated with a fatal outcome within 100 days: advanced age, presence of a pulmonary focus, occurrence of convulsions, undergoing a CT scan before lumbar puncture, and the requirement for assisted ventilation. Conversely, an otogenic focus of infection was associated with improved survival.[14] In pediatric populations, retrospective analyses have shown that coma, respiratory failure, shock, and leukopenia (white blood cell count <4000/mm^3) at presentation are poor prognostic factors.[19] Mortality rates for neonatal GBS meningitis have declined with the widespread implementation of intrapartum antibiotic prophylaxis. However, mortality remains significant, with a reported rate of 11.4% among 848 neonates studied.[33]

Among survivors of streptococcal meningitis, as well as those with pneumococcal and GBS, neurological and systemic sequelae are common. They may include cognitive impairment, hearing loss, motor deficits, and seizure disorders, underscoring the importance of early diagnosis and aggressive management. These long-term complications can significantly impact quality of life and developmental outcomes, particularly in pediatric patients.

Complications

The incidence of neurological sequelae among survivors of pneumococcal meningitis remains high. In a study by Kastenbauer et al, intracranial complications associated with meningitis were observed in 74.7% of adults, while systemic complications affected more than one-third. Reported neurological complications included seizures (27.6%), diffuse brain swelling (28.7%), hearing loss (19.7%), ischemic or hemorrhagic brain damage (21.8%), and hydrocephalus (16.1%).[34] Similarly, in a study by Van De Beek et al, focal neurological deficits were identified in 65% of patients with pneumococcal meningitis, with hearing impairment being the most frequently reported sequela.[12] These findings underscore the substantial burden of long-term complications and emphasize the need for comprehensive follow-up care in individuals affected by this condition.

Developmental delay was the frequently reported long-term sequela following pneumococcal meningitis, affecting 43% of the enrolled pediatric patients.[26] Nearly one-third of survivors experienced seizures 1 year after the infection, and hearing loss was documented in 29% of the children. These findings emphasize the lasting impact of pneumococcal meningitis on neurodevelopmental outcomes in the pediatric population. Long-term morbidity among survivors of GBS meningitis is significant. Approximately 25% of affected children exhibit mild to moderate neurodevelopmental impairment, while nearly 20% demonstrate severe deficits upon follow-up assessment.[35]