Streptococcal meningitis is an acute inflammation of the membranes surrounding the brain and spinal cord caused by bacteria from the streptococcal species. Bacterial meningitis is a severe and life-threatening infection that may lead to death, especially when treatment initiation is overdue. Despite progress in diagnostic methods and treatment as well as the implementation of national immunization programs, bacterial meningitis is still one of the most burdening infectious diseases worldwide.
Numerous Streptococcus bacteria can cause meningitis. The most significant one is Streptococcus pneumoniae, probably the leading etiologic agent of meningitis worldwide, both in adults and children. In the beta-hemolytic group, the most notable is group B Streptococcus (GBS) – the most common cause of meningitis in neonates and young infants. Other streptococci, i.e., belonging to the S. viridans group or group A are very rarely causative pathogens of meningitis in adults or children.
The etiologic agents causing streptococcal meningitis vary by age group. Streptococcus pneumoniae remains the most common etiologic agent of bacterial meningitis in children above one month and adults of all ages. In the U.S., the incidence of pneumococcal meningitis decreased from 0.8 per 100000 people in 1997 to 0.3 per 100000 people in 2010 (PCV 7 was introduced in 2000). S. pneumoniae infection is also the most common cause of bacterial meningitis in children, ranging from 22.5% in Europe to 41.1% in Africa. In the developing world, invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality, with up to 1.0 million deaths per year in children less than five years old.
In neonates, S. agalactiae is one of the leading pathogens responsible for meningitis. In the U.S., from 2006 to 2015, early-onset disease (onset at 0 to 6 days of life, EOD) incidence decreased from 0.37 to 0.23 per 1000 live births, mainly due to intrapartum antibiotic prophylaxis. Late-onset disease (LOD) rates were stable in those years. The global incidence of invasive GBS disease in infants is 0.49 per 1000 live births with the highest numbers in Africa. Other groups of streptococci rarely cause meningitis. S. viridans accounts for 0.3% to 3.0% of cases of bacterial meningitis in adults and 1% in children. Group A streptococcal meningitis was diagnosed in 2% of the cases of community-acquired bacterial meningitis.
Meningitis occurs when bacteria enter the bloodstream and then cross the blood-brain barrier or through direct contact of meninges with the skin or nasal cavity. The most frequent focus of the infection is nasopharynx colonized by S. pneumoniae that evades the host immune system. During IPD, the bloodstream becomes invaded, and complement and coagulation systems are activated. Inflammatory mediators are released massively, which makes it easier for the bacteria to cross the blood-brain barrier. Inflammation is responsible for all the typical findings of bacterial meningitis, i.e., CSF pleocytosis.
Symptoms of bacterial meningitis, including Streptococcal, can develop either suddenly or over a few days. Typically they are present 3 to 7 days after exposure. There are no specific symptoms that allow recognition of causative agents of bacterial meningitis based solely on history taking and examination.
The classic triad of diagnostic symptoms of meningitis in adults includes fever, nuchal rigidity, and altered mental status; however, only 44% of adult patients with bacterial meningitis present with all three symptoms. In the same study, nearly all patients had a minimum of two out of four symptoms among headache, fever, neck stiffness, and altered mental status. Other complaints typically reported by patients are severe headache, intensified by head movements, nausea, vomiting, and photophobia. In the study by Lucht accuracy of clinical examination for the diagnosis of meningitis in adults was reviewed. Sensitivity for clinical signs like headache, vomiting, or fever was less than 30% and for nuchal rigidity, 45%. The study also showed that if two out of four signs among headache, fever, altered mental status, and neck stiffness are absent, the diagnosis of meningitis is extremely unlikely (with the negative predictive value of 95%). A Danish study enrolled adults with pneumococcal meningitis. On admission, researchers observed fever and an altered mental status in almost all cases. Back rigidity, headache, and convulsions were found less commonly (57%, 41%, and 11%, respectively).
On physical examination, signs of meningeal irritation can be present - nuchal rigidity, Kernig's, and Brudzinski's signs. Those signs have high specificity in patients with meningitis. However, their sensitivity is low. In a study conducted by Thomas et al. that analyzed adults with meningitis suspicion, researchers reported the specificity of 95% and sensitivity of 5% for both Kernig's and Brudzinski's signs, as well as a sensitivity of 30% and specificity of 68% for nuchal rigidity. Altered mental status is observable – confusion decreased alertness or even seizures.
Clinical signs of neonatal and infant meningitis are usually non-specific, including irritability or lethargy, fever or hypothermia, poor feeding, and vomiting with diarrhea. More specific signs on the physical examination like bulging fontanel, nuchal rigidity, and seizures in neonates are usually late findings. In the study of Amarilyo et al., half of the enrolled patients with meningitis with open fontanel had bulging fontanel. This study enrolled children aged two months to 16 years with suspected meningitis - Kernig's and Brudzinski's signs had a sensitivity of 27% and 51%, respectively, with the high positive predictive value of 77% and 81%, respectively. Classic meningeal signs are often absent in infants less than six months. Weber et al. proved that reduced feeding, the appearance of being very sick, being lethargic or unconscious, neck stiffness, and a bulging fontanel are the variables associated independently with meningitis in children aged two months to 3 years.
The pivotal test for diagnosis of meningitis (including streptococcal one) is cerebrospinal fluid (CSF) examination. It is required to confirm the diagnosis, identify the causative bacterial pathogen, and, therefore, to implement de-escalated treatment later on. CSF should be obtained as soon as the bacterial meningitis is suspected unless contraindications for urgent lumbar puncture (LP) are present. Contraindications for immediate LP include risk of herniation, uncorrected coagulopathy, or critical condition of the patient. According to the Infectious Diseases Society of America guidelines, head CT before LP is warranted in the case of focal neurologic deficit, abnormal level of consciousness, papilledema, seizure within one week of presentation, history of central nervous system disease and an immunocompromised state. During LP, samples of CSF are taken and sent for physical and chemical characteristics, cell count, Gram stain, latex agglutination test (LAT), culture, and, if available, PCR. CSF examination in patients with streptococcal meningitis usually shows neutrophilic pleocytosis (white blood count of 500/ microL or higher), elevated lactate level, and lowered CSF/serum glucose ratio. CSF leukocyte count less than 50/mm^3 and elevated CSF protein level (at least 660 mg/dL) were poor prognostic factors in children with pneumococcal meningitis. CSF Gram staining results in the initial identification of bacteria. LAT detects antigens of few pathogens, among them S. pneumoniae. Results are provided in a short time. The causative pathogen is confirmed by positive culture from the CSF sample; however, in a study comparing traditional culture and antigen detection methods, less than half of the cases of bacterial meningitis were culture positive. Another option was PCR, especially valid when previously using antibiotics. The use of the PCR test in determining the etiology of bacterial meningitis is increasing. However, it recognizes only several types of bacteria – the ones included in the primer mix. In the previously mentioned study, LAT proved to be more sensitive compared to conventional Gram stain and Culture technique in identifying the specific organisms like H. influenzae, S. pneumoniae, and Group B Streptococcus. Nevertheless, the combination of culture, Gram stain, and LAT was more effective than any of the single methods alone.
Other laboratory tests include blood culture – necessary to take to increase the likelihood of identification of causative pathogen - as well as complete blood count, inflammatory markers (often much elevated), coagulation testing, markers of liver and kidney function. There should be no delays in instituting treatment because of all the diagnostic procedures.
Streptococcal meningitis requires immediate treatment with antibiotics. Delays in implementing treatment are not acceptable.
Initial treatment for pneumococcal meningitis consists of vancomycin plus one of the third-generation cephalosporins: cefotaxime or ceftriaxone. The antibiotic therapy can undergo review after antibiotic sensitivity is available – if bacteria is penicillin-susceptible, switch to penicillin is acceptable. For patients with a history of anaphylaxis to cephalosporins or penicillins, chloramphenicol is an option. Adjuvant therapy with dexamethasone is recommended - research showed a significant reduction in mortality, and all unfavorable outcomes in patients with pneumococcal meningitis compared to sole antibiotic treatment.
Penicillin G monotherapy is suitable for the treatment of meningitis caused by GBS. Ampicillin is an acceptable alternative.
S. viridans, Group A Streptococcus
Penicillin G is effective for the treatment of meningitis caused by S. viridans or group A Streptococcus.
Supportive care, including fluid management, reduction of intracranial pressure, antipyretics, and analgesics, are a valid part of the therapy.
Diseases that merit consideration in the differential diagnosis are other neural infections. Meningitis of different bacterial etiology (i.e., meningococcal) can be mistaken for streptococcal meningitis. It is impossible to establish the etiology taking into consideration only the clinical picture. CSF culture is indispensable in making a precise diagnosis. Viral and fungal etiologies of meningitis must also be ruled out. Encephalitis is another disease that can present itself very similarly to meningitis. Although encephalitis can affect meninges as well, evidence of brain inflammation is the distinguishing feature absent in meningitis. All other causes of altered mental status and coma should be ruled out, including stroke, intoxication, hypoglycemia, and electrolyte disturbances.
Prognosis in streptococcal meningitis is always serious. In a Danish study of pneumococcal meningitis, the overall case-fatality rate was 21%, with a 10-fold higher mortality rate in adults than in children. The causes of death were neurological, such as brain herniation, cerebrovascular complications (41% of the patients), systemic causes like septic shock, multiple-organ dysfunction (nearly one-fourth), other causes (8%) and roughly one-third died due to a combination of systemic and neurological complications. Advanced age, presence of lung focus, convulsions, having a CT-scan before lumbar puncture, and need of assisted ventilation were prognostic factors associated with a fatal outcome within 100 days. The otogenic focus was associated with better survival. Retrospective analysis showed that the initial presentation of coma, respiratory failure, shock, and leukopenia (WBC less than 4,000/mm^3) were poor prognostic factors in children with meningitis. Mortality rates for GBS meningitis in neonates decreased following the introduction of intrapartum chemoprophylaxis. However, it remains high (11.4% among 848 patients enrolled). Neurological and systemic sequelae in survivors are common.
The incidence of neurological sequelae in survivors of pneumococcal meningitis remains high. Kastenbauer et al., in their study of adults, showed that meningitis-associated intracranial complications concerned 74.7% of the patients after pneumococcal meningitis and systemic complications touched over one-third of the patients. Some of the complications were seizure (27.6%), diffuse brain swelling (28.7%), hearing loss (19.7%), ischemic or hemorrhagic brain damage (21.8%), and hydrocephalus (16.1%). In Van De Beek's study, researchers found focal neurological deficits in 65% of the patients with pneumococcal meningitis, with the most common one being hearing impairment.
In children, the developmental delay was the most common long-term post-pneumococcal meningitis sequelae concerning 43% of the enrolled children. In almost one-third of survivors, seizures were observed at one year postinfection. Hearing loss occurred in 29% of the children.
Long-term morbidity in survivors of GBS meningitis is significant. One-fourth of the children with GBS meningitis had a mild-to-moderate impairment, almost 20% showed severe impairment when assessed later.
Patient education about Streptococcal meningitis, including alarming symptoms, is vital to provide the best possible outcome. Treatment delay is an unfavorable factor in bacterial meningitis. Pregnant women should be informed by their obstetrician about possible intrapartum chemoprophylaxis.
S. pneumoniae spreads through respiratory droplets from people with Pneumococcal disease or healthy carriers who have the bacteria in their nasopharynx. However, there is a little chance of having pneumococcal meningitis even after close contact. There are individual factors that make the person vulnerable to the development of pneumococcal meningitis, including immunocompromised, especially patients with asplenia, diabetes, leak of cerebrospinal fluid, cochlear implant, history of meningitis, cigarette smoking, and alcohol use.
GBS is a common finding in gastrointestinal and genital tracts. Women who become colonized with this bacteria can pass it on to their newborns during labor. In adults, most of the GBS meningitis is found in patients with comorbid conditions.
Among all streptococcal meningitides, only pneumococcal is a vaccine-preventable condition. Two types of vaccines exist against Streptococcus pneumoniae available: older pneumococcal polysaccharide vaccine (PPSV) and newer pneumococcal conjugate vaccines (PCV). PPSV is composed of 23 pneumococcal capsular polysaccharides, and it covers the broadest range of antigens out of all pneumococcal vaccines. Children less than two years old do not respond to this vaccination, though; therefore, it is suitable only for patients over two years of age. In the meta-analysis by Falkenhorst et al., PPSV23 efficacy against IPD caused by any serotype was reported to be 73% in a pooled analysis of all included clinical trials enrolling adults aged above 60 years living in industrialized countries. PCV contains pneumococcal capsular polysaccharides linked to a carrier protein that allows the immune system of infants to produce antibodies. The recommendation is to use PCV in the children's routine immunizations. There are two types of PCV available with a different number of serotypes: PCV10 and PCV13. Lucero et al. conducted a meta-analysis of six randomized trials of different valencies of PCV. In children of less than two years of age, the efficacy of PCV for preventing vaccine-type IPD was 80%, and 58% for preventing IPD caused by all serotypes. The CAPiTA trial assessed the efficacy of PCV13 with immunocompetent adults above 65 years of age enrolled. Results demonstrated about 75% efficacy against the vaccine-type invasive pneumococcal disease.
Meningitis caused by group B streptococci is also preventable by testing all pregnant women at 35 to 37 weeks of gestation for vagina and rectum colonization with GBS and using antibiotic chemoprophylaxis in colonized women. Approximately half of the colonized women will pass the bacteria to their neonates during labor or after membranes' rupture. If not for intrapartum antibiotic prophylaxis, up to 2% of those newborns will develop GBS EOD. Since the implementation of national guidelines in the USA for intrapartum prophylaxis, statistics show a reduction in the occurrence of GBS EOD of more than 80% between the early 1990s and 2010.
Streptococcal meningitis is a severe, life-threatening infection. It may pose a diagnostic challenge, especially in infants, because these patients may exhibit non-specific signs. The most vital for a patient outcome is fast diagnosis and treatment. Doctors who work in ambulatory care facilities should educate their patients about alarming symptoms of meningitis. While the pediatrician or internist is almost always involved in the care of patients with streptococcal meningitis, it is essential to cooperate with other specialists that include infectious disease expert, or anesthesiologist if needed. The nurses are also a vital member of the interprofessional group, as they will monitor the patient's vital signs. Laboratory professionals play an essential role in establishing the diagnosis of causative agents. A physiotherapist is also needed to reduce the neurological burden of streptococcal meningitis. A board-certified infectious disease pharmacist can review antibiotic choices with the clinician, using the latest antibiogram data. They can also check for interactions, verify dosing and duration, and communicate with the rest of the team regarding potential adverse events. Interprofessional team efforts are necessary to improve outcomes for patients. [Level 5]
|||Castelblanco RL,Lee M,Hasbun R, Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study. The Lancet. Infectious diseases. 2014 Sep; [PubMed PMID: 25104307]|
|||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; [PubMed PMID: 29889859]|
|||Brouwer MC,Tunkel AR,van de Beek D, Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clinical microbiology reviews. 2010 Jul; [PubMed PMID: 20610819]|
|||Nanduri SA,Petit S,Smelser C,Apostol M,Alden NB,Harrison LH,Lynfield R,Vagnone PS,Burzlaff K,Spina NL,Dufort EM,Schaffner W,Thomas AR,Farley MM,Jain JH,Pondo T,McGee L,Beall BW,Schrag SJ, Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance. JAMA pediatrics. 2019 Mar 1; [PubMed PMID: 30640366]|
|||Madrid L,Seale AC,Kohli-Lynch M,Edmond KM,Lawn JE,Heath PT,Madhi SA,Baker CJ,Bartlett L,Cutland C,Gravett MG,Ip M,Le Doare K,Rubens CE,Saha SK,Sobanjo-Ter Meulen A,Vekemans J,Schrag S, Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2017 Nov 6; [PubMed PMID: 29117326]|
|||Birlutiu V,Birlutiu RM,Costache VS, Viridans streptococcal infective endocarditis associated with fixed orthodontic appliance managed surgically by mitral valve plasty: A case report. Medicine. 2018 Jul; [PubMed PMID: 29979391]|
|||Lucas MJ,Brouwer MC,Bovenkerk S,Man WK,van der Ende A,van de Beek D, Group A Streptococcal meningitis in adults. The Journal of infection. 2015 Jul; [PubMed PMID: 25614959]|
|||van de Beek D,de Gans J,Spanjaard L,Weisfelt M,Reitsma JB,Vermeulen M, Clinical features and prognostic factors in adults with bacterial meningitis. The New England journal of medicine. 2004 Oct 28; [PubMed PMID: 15509818]|
|||Lucht F, [Sensitivity and specificity of clinical signs in adults]. Medecine et maladies infectieuses. 2009 Jul-Aug; [PubMed PMID: 19632074]|
|||Østergaard C,Konradsen HB,Samuelsson S, Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection. BMC infectious diseases. 2005 Oct 27; [PubMed PMID: 16253143]|
|||Thomas KE,Hasbun R,Jekel J,Quagliarello VJ, The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2002 Jul 1; [PubMed PMID: 12060874]|
|||Ku LC,Boggess KA,Cohen-Wolkowiez M, Bacterial meningitis in infants. Clinics in perinatology. 2015 Mar; [PubMed PMID: 25677995]|
|||Amarilyo G,Alper A,Ben-Tov A,Grisaru-Soen G, Diagnostic accuracy of clinical symptoms and signs in children with meningitis. Pediatric emergency care. 2011 Mar; [PubMed PMID: 21346676]|
|||Weber MW,Herman J,Jaffar S,Usen S,Oparaugo A,Omosigho C,Adegbola RA,Greenwood BM,Mulholland EK, Clinical predictors of bacterial meningitis in infants and young children in The Gambia. Tropical medicine [PubMed PMID: 12225501]|
|||Ma JS,Chen PY,Mak SC,Chi CS,Lau YJ, Clinical outcome of invasive pneumococcal infection in children: a 10-year retrospective analysis. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2002 Mar; [PubMed PMID: 11950116]|
|||Mohammadi SF,Patil AB,Nadagir SD,Nandihal N,Lakshminarayana SA, Diagnostic value of latex agglutination test in diagnosis of acute bacterial meningitis. Annals of Indian Academy of Neurology. 2013 Oct; [PubMed PMID: 24339598]|
|||Brouwer MC,Heckenberg SG,de Gans J,Spanjaard L,Reitsma JB,van de Beek D, Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis. Neurology. 2010 Oct 26; [PubMed PMID: 20881273]|
|||de Gans J,van de Beek D, Dexamethasone in adults with bacterial meningitis. The New England journal of medicine. 2002 Nov 14; [PubMed PMID: 12432041]|
|||Romain AS,Cohen R,Plainvert C,Joubrel C,Béchet S,Perret A,Tazi A,Poyart C,Levy C, Clinical and Laboratory Features of Group B Streptococcus Meningitis in Infants and Newborns: Study of 848 Cases in France, 2001-2014. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Mar 5; [PubMed PMID: 29045606]|
|||Kastenbauer S,Pfister HW, Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases. Brain : a journal of neurology. 2003 May; [PubMed PMID: 12690042]|
|||Stockmann C,Ampofo K,Byington CL,Filloux F,Hersh AL,Blaschke AJ,Cowan P,Korgenski K,Mason EO,Pavia AT, Pneumococcal meningitis in children: epidemiology, serotypes, and outcomes from 1997-2010 in Utah. Pediatrics. 2013 Sep; [PubMed PMID: 23979090]|
|||Libster R,Edwards KM,Levent F,Edwards MS,Rench MA,Castagnini LA,Cooper T,Sparks RC,Baker CJ,Shah PE, Long-term outcomes of group B streptococcal meningitis. Pediatrics. 2012 Jul; [PubMed PMID: 22689869]|
|||Falkenhorst G,Remschmidt C,Harder T,Hummers-Pradier E,Wichmann O,Bogdan C, Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis. PloS one. 2017; [PubMed PMID: 28061505]|
|||Lucero MG,Dulalia VE,Nillos LT,Williams G,Parreño RA,Nohynek H,Riley ID,Makela H, Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age. The Cochrane database of systematic reviews. 2009 Oct 7; [PubMed PMID: 19821336]|
|||Bonten MJ,Huijts SM,Bolkenbaas M,Webber C,Patterson S,Gault S,van Werkhoven CH,van Deursen AM,Sanders EA,Verheij TJ,Patton M,McDonough A,Moradoghli-Haftvani A,Smith H,Mellelieu T,Pride MW,Crowther G,Schmoele-Thoma B,Scott DA,Jansen KU,Lobatto R,Oosterman B,Visser N,Caspers E,Smorenburg A,Emini EA,Gruber WC,Grobbee DE, Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. The New England journal of medicine. 2015 Mar 19; [PubMed PMID: 25785969]|
|||Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 782. Obstetrics and gynecology. 2019 Jul; [PubMed PMID: 31241599]|
|||Schrag SJ,Verani JR, Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine. 2013 Aug 28; [PubMed PMID: 23219695]|