Bacterial meningitis can be community-acquired, or it may be associated with some treatment (usually a neurosurgical procedure). This article deals with community-acquired bacterial meningitis.
Bacterial meningitis should always be suspected in a patient with fever and meningeal symptoms, such as headache, neck stiffness and decreased level of consciousness.
The antimicrobial treatment of an acute bacterial meningitis must be started immediately.
As soon as the bacteriological aetiology is established, antimicrobial pharmacotherapy is directed according to the aetiology.
An aseptic meningitis is much more common than bacterial meningitis. Its symptoms are milder, and it very seldom causes an impairment of consciousness.
Slowly progressing meningitis should be suspected in patients with general symptoms and impaired consciousness, even when neck stiffness is absent.
Acute community-acquired bacterial meningitis
In adults the most significant causes are Neisseria meningitidis (or "meningococcus") and Streptococcus pneumoniae (or "pneumococcus").
More rare causative agents include Staphylococcus aureus, gram-negative rods and listeria.
The three classical symptoms, i.e. fever, neck stiffness and decreased level of consciousness, are seen in less than half of the patients only.
At least two of the following symptoms are seen in 95% of the patients: headache, fever, neck stiffness and decreased level of consciousness.
Lack of neck stiffness does not rule out meningitis.
In very young or very old patients the symptom picture may deviate from the usual: the only symptom of a bacterial meningitis may be poor general condition either with or without a decreased level of consciousness.
Diagnosis
Clinical picture
A cerebrospinal fluid sample Lumbar Puncture and two samples for culture of blood should be obtained before starting antimicrobial treatment.
Antimicrobial therapy and dexamethasone 0.15 mg/kg intravenously 4 times daily are started before taking the samples if the distance to a facility with the possibility for sample-taking is long.
Antimicrobial therapy and dexamethasone are started right after taking the blood cultures, if a CT scan of the head is indicated before taking a liquor sample or if a spinal tap is contraindicated (e.g. thrombocyte count < 50 × 109 /l).
Examination of cerebrospinal fluid
If the cerebrospinal fluid is opaque, a bacterial meningitis is very likely.
Differential white cell count, glucose, protein, bacterial staining and bacterial culture are examined Lumbar Puncture. If antimicrobial pharmacotherapy was started before CSF sample was taken, bacterial PCR testing should also be performed.
Typical cerebrospinal fluid findings
Leucocytes 1 000-5 000 × 106 /l
The majority of the leucocytes are polymorphonuclear, usually more than 60-80%.
Glucose concentration low, < 2 mmol/l, or CSF/serum glucose ratio < 0.4
Protein concentration is increased to > 1 000 mg/l.
At the initial stage, the cell reaction may not have fully developed.
Ceftriaxone 2 g × 2 i.v. and vancomycin 15 mg/kg × 2 i.v. are started as empirical medication. If, based on bacterial staining, there is no suspicion of pneumococcal disease, there is no need to start vancomycin or it can be discontinued.
If the patient has risk factors for listeria infection (age > 50 years, alcoholism, immunosuppression), the initial empirical medication consists of ceftriaxone 2 g × 2 i.v., vancomycin 15 mg/kg × 2 i.v. and ampicillin 2 g × 6 i.v.
The definitive antimicrobial therapy is chosen when the causative agent and its antimicrobial sensitivity have been clarified.
Dexamethasone is discontinued if the causative agent is found to be else than pneumococcus.
Either G-penicillin 4 million IU × 6 i.v. or ceftriaxone 2 g × 2 i.v. can be used for meningococcal or pneumococcal meningitis, taking into account the sensitivity testing.
In listeria meningitis, ampicillin 2 g × 6 i.v. can be used combined with gentamycin with a starting dose of 2 mg/kg i.v., and as maintenance dose 1.7 mg/kg i.v. 3 times daily; in patients with penicillin allergy, meropenem 2 g × 3 i.v. is an alternative.
In staphylococcal meningitis, cloxacillin 2 g × 6 i.v.
Meningitis caused by Escherichia coli can be treated with ceftriaxone 2 g × 2 i.v., taking into account the sensitivity testing.
If the aetiology is meningococcal or such aetiology is suspected, droplet isolation is implemented for 24 hours from the onset of antimicrobial medication.
Preventive antimicrobial medication is given from the hospital to close relatives (living in the same household or otherwise being in close contact) and to those health care workers who have been exposed to oral or pharyngeal secretions. Other contact tracing is performed by the local physician responsible for infection control.
If the disease is caused by listeria, dexamethasone should be stopped.
Duration of treatment
The minimum duration of treatment is
10-14 days in pneumococcal infections
7 days in meningococcal infections
21-28 days in listeria and enterococcal infections.
Acute viral meningitis (aseptic meningitis)
Much more common than bacterial meningitis.
Inflammation of the cranial meninges where no bacterial, parasitic or fungal aetiology can be found.
Often involves a postinfectious immunological mechanism.
In more than half of the cases the aetiology remains unknown.
Clinical picture is self-limited. The majority will heal with symptomatic treatment (rest, treatment of pain and nausea)
Of the identified causative agents, the most common are enteroviruses.
Onset is most common in the autumn and early winter when epidemics of respiratory viruses and enteroviruses appear.
It is essential to investigate the presence of any diseases that weaken the patient's immune defences and any medication for such diseases, as well as the patient's lifestyle, nutritional state, possible contact with ticks and whether the patient has been engaged in sexual risk behaviour.
In young individuals in association with HSV-2 primary infection
HSV-2 is also the most common cause of recurrent aseptic meningitis in adults.
In association with VZV shingles; can be found through careful examination of patient's skin.
TBE in risk areas (in some countries wild reindeers and deers have expanded their distribution: ask about travels)
Also pharmaceuticals can cause aseptic meningitis (NSAIDs, sulpha drugs and intravenous immunoglobulin).
Also in association with mumps in unvaccinated persons; in such cases concomitant orchitis may be present.
The possibility of HIV infection should be kept in mind in patients with risky behaviours.
Symptoms
These develop more slowly than in bacterial meningitis, and the patient's general condition is often clearly better. In young patients the symptoms are more severe with headache and fever as the predominant symptoms, whereas in older patients the symptoms are milder with fatigue and nausea as the predominant symptoms.
Patient history: travelling, unprotected sex, nutrition, staying in areas with ticks?
In investigating the symptom picture it is important to find out about the start and development of symptoms, as well as any concurrent or preceding other symptoms, such as respiratory, bowel, skin, mucosal and joint symptoms.
Headache
Nausea and vomiting
Fatigue
Neck stiffness is common, but not necessarily present.
Confusion, impairment of consciousness and focal symptoms are not a part of the typical symptom picture (suspect encephalitis, brain abscess or bacterial meningitis).
Diagnosis
Clinical picture, development of symptoms and the patient's general status
CRP is often normal or only slightly elevated.
Lumbar puncture is performed at discretion in order to rule out bacterial meningitis and treatable aetiologies.
In patients with severe symptoms, immunosuppressed patients and patients recovering from cranial surgery, even if the cerebrospinal fluid is clear, it is advisable to take samples for bacterial stain and culture. Tuberculosis stain and culture are performed at discretion.
In addition, 2-5 ml of spinal fluid should be stored for potential later virological and serological testing, as deemed necessary. The sample can be used for further testing within a period of 2 weeks.
Typical cerebrospinal fluid findings
Leucocytes 20-200 × 106 /l, often almost exclusively mononuclear, in a sample taken at the very initial phase also polymorhonuclear
Glucose concentration is over 2 mmol/l. A low glucose concentration always necessitates further investigations.
Proteins generally under 1000 mg/l
Treatment
Treatment is symptomatic. If hospitalization is needed and adequate oral fluid intake is unfeasible, intravenous fluid therapy is started.
For nausea methoclopramide, for headache an NSAID, using sufficiently high doses.
A decision about the appropriate treatment location should be based on the final diagnosis and the general condition of the patient. Home care is suitable for patients with mild symptoms, depending on the circumstances and the patient's condition.
If symptoms persist, increase or become more severe, repeated diagnostic evaluation is necessary.
Subacute and chronic meningitis
Causes
Borrelia (slowly within weeks-months developing symptoms, neuralgias in the neck, back)
Tuberculosis (often in persons coming from countries with high incidence rate)
These patients should always be referred to a hospital with sufficient resources for investigations and treatment.
Tuberculous meningitis
Today this condition tends to be rare in many countries, the patient often comes from a country with a high incidence rate.
It is an important possibility to bear in mind, because early treatment is crucial; without treatment the mortality is high.
In suspicion of tuberculous meningitis the patient should be referred to a hospital.
A history of recent tuberculosis or having had tuberculosis before eradication treatment (including tuberculosis in a close person) is possible but not necessary.
Symptoms develop usually slowly in 1-2 weeks. Symptoms include clouding of consciousness, personality changes, symptoms of meningeal irritation and cranial nerve pareses.
Treatment must be initiated on the grounds of a strong suspicion and the clinical picture.
Cerebrospinal fluid findings
The findings are the same as in viral meningitis (mononuclear pleocytosis), with the exception of glucose concentration which is decreased (< 2 mmol/l) and protein concentration which is increased. In judging the glucose concentration, also the blood glucose levels should be considered.
Diagnostic problems are caused by the unreliability of the acid-fast stains, or if the confirmation based on the culture will be too late to be of use in treatment decisions.
PCR assay of the CSF is more sensitive than CSF staining (positive in 5-30% only) for tuberculosis. The test result is available within a few days.
A chest x-ray is always evaluated with also tuberculosis in mind. Taking into account the results of clinical findings and laboratory and imaging studies, tuberculosis stains and culture are also performed on the sputum and urine.
Treatment duration is usually 12-24 months. The duration depends on both the severity of the disease and the causative agent's sensitivity to drugs.
Fungal meningitis
The condition is very rare, usually affecting patients with severely compromized immune system (AIDS, haematological malignancy, organ transplant patients, immunosuppressive medication).
Causes include Candida, Cryptococcus and Aspergillus.
The manifestation of the disease resembles meningeal tuberculosis.
Cerebrospinal fluid findings
Similar to those in tbc meningitis, but the cellular content may also include some polymorphonuclear leucocytes.
Diagnosis is based on detecting fungus in the cerebrospinal fluid (smear, culture, antigen or nucleic acid detection).
Borrelia meningitis
Symptoms of early neuroborreliosis usually appear 1-2 months after a tick bite. Erythema migrans rash is mostly not present in patients with neuroborreliosis.
Nowadays erythema migrans is often recognized and well treated, and consequently neuroborreliosis will not develop.
Seasonal and geographical variation exists in the incidence of neuroborreliosis. In Northern Europe, the disease is most common between May and January (see e.g. http://www.nature.com/articles/s41598-020-64638-5). Find out about local epidemiology.
The bite may often remain unnoticed; nymphs are almost invisible.
Symptoms
The most common symptoms
Symptoms of meningeal irritation (mild headache, feeling heavy, feeling ill)
Fatigue
Painful neuralgias that change location (radiculitis)
Facial nerve palsy (sometimes bilateral)
Also symptoms of meningitis developing within a few weeks-months are possible: mostly mild headache and fever.
Cerebrospinal fluid findings
Cell counts are similar to those in viral meningitis, and glucose concentration is mostly normal.
Protein concentrations in the cerebrospinal fluid are often increased, > 1000 mg/l.
The IgG index of the cerebrospinal fluid may be elevated (normal value < 0.60). This is not, however, needed in diagnostics.
Borrelia antibodies, using both serum and CSF samples, are usually determined (intrathecal antibody synthesis index is calculated: > 2 suggests intrameningeal antibody production)Lyme Borreliosis (LB). Their concentrations are usually increased in both samples, but occasionally in only one of them.
CSF CXCL13 concentration is usually increased in acute infection and works well as a biomarker of neuroborreliosis. It can be used in special situations.
Detecting borrelia nucleic acid in CSF is specific, but the test is rarely positive and hence it is not a routine examination.
Treatment
Diagnosis can be classified as definite, probable and possible neuroborreliosis.
In definite neuroborreliosis, there is a typical symptom picture, CSF findings, intrathecal antibody index > 2 and other aetiologies have been excluded in a sufficient manner.
Treatment of neuroborreliosis may be started before the results of antibody tests are available, if the patient is known to have a tick contact or if he/she has stayed in an area endemic for ticks and the clinical picture and CSF findings are compatible with neuroborreliosis. If antibodies are negative or another aetiology is found for the symptoms, antimicrobial therapy is discontinued.
The first-line therapy is oral doxycycline 100 mg twice daily for 28 days. In rare cases with clinical pictures involving severe CNS symptoms, the treatment is intravenous ceftriaxone 2 g once daily for 14-21 days.
Other chronic types of meningitis
Most important of these are the meningitis associated with connective tissue diseases, secondary syphilis and neurosarcoidosis, as well as a carcinoma (melanoma, adenocarcinomas, breast cancer, glioblastoma) and lymphoma that has spread into the meninges.
Treponema pallidum antibodies is the screening test for syphilis. If the test is positive, serum and CSF samples should be taken at the same time to perform anti-cardiolipin antibodies and treponema pallidum haemagglutination (TPHA) tests and, as necessary, CSF FTA absorption test.
If malignant cells are detected, cytological examination of the CSF should be performed, using several repeated samples. Tumour cells do not alway transfer to the CSF even though they grow on the meninx. In such cases the clinical picture and contrast-enhanced MRI demonstrate the spread of the disease.
If lymphoma is suspected, CSF surface markers (haematological laboratory), CSF cytology and CSF blast cells should be examined.
References
McGill F, Heyderman RS, Panagiotou S ym. Acute bacterial meningitis in adults. Lancet 2016;388(10063):3036-3047. [PubMed]
van de Beek D, Cabellos C, Dzupova O ym. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016;22 Suppl (3):S37-62. [PubMed]
Wright WF, Pinto CN, Palisoc K ym. Viral (aseptic) meningitis: A review. J Neurol Sci 2019;(398):176-183. [PubMed]