Acute bacterial meningitis

Acute bacterial meningitis is a fulminant, often fatal purulent infection of the membranes of the brain.

The main symptoms of the disease are headache, fever and stiff neck. Without emergency treatment, stun and coma develop. The diagnosis is based on the results of the CSF analysis. Antibiotic therapy with cephalosporins of the 3rd and 4th generation, vancomycin and ampicillin at the onset of the disease is usually empirical; additionally assigned glucocorticoids. The mortality rates remain high.

[1], [2], [3], [4], [5], [6],

What causes acute bacterial meningitis?

Many bacteria are capable of causing meningitis, but the leading pathogens during the first two months of life are group B Streptococcus, followed by Neisseria meningitidis (meningococci) and Streptococcus pneumoniae (pneumococci). Meningococci is found in the nasopharynx in about 5% of people; they spread by airborne and by contact. For unclear reasons, only a small proportion of carriers are ill with meningitis.

Meningococcal meningitis is most often affected by children of the first year of life. The disease also tends to grow into an epidemic in closed collectives (in army barracks, student hostels, boarding schools).

In adults, pneumococci are the most frequent cause of meningitis. Patients with chronic otitis, sinusitis, mastoiditis, recurrent meningitis, pneumococcal pneumonia, sickle-cell anemia, persons with asplenia [aplasia of the spleen] and cerebrospinal fluid, as well as alcohol abusers, are at high risk. The prevalence of pneumococcal meningitis is reduced due to the introduction of vaccination.

Meningitis of gram-negative etiology (predominantly Escherichia coli, Klebsiella spp., And Enterobacter spp.) Is most likely in individuals with immunodeficiency conditions, after CNS and brain injury, bacteremia (for example, after manipulation on the genitourinary tract) or infection with nosocomial infection . In persons with immunodeficiency states and in some populations, agents of the genus Pseudomonas may be the causative agent of meningitis . Haemophilus influenzae type B as a causative agent of bacterial meningitis currently occurs rarely due to widespread vaccination, but sometimes it is isolated in individuals with immunodeficiency, after traumatic brain injury and in unvaccinated individuals.

Staphylococcal meningitis can develop after penetrating wounds to the head, neurosurgical interventions (often as a combination infection) or bacteremia (in endocarditis patients). Listeriosis meningitis can develop at any age, more often in persons with immunosuppression against a background of chronic renal infection, liver dysfunction or treatment with glucocorticoids or cytostatics after organ transplantation.

Bacteria reach the membranes of the brain usually by hematogenous way from places of colonization in the nasopharynx or other foci of infection (for example, pneumonia). Tropicity of bacteria to the CSF is not fully understood, however, the ability of bacteria to encapsulate and the presence of fixating cilia play a certain role in the colonization process. The presence of receptors in the choroidal plexus of the cilia and other surface structures of bacteria facilitates the penetration of bacteria into the liquor-containing spaces.

Bacteria can enter the CSF by contact, spreading from a nearby source of infection (eg sinusitis, mastoiditis), or in cases of contact between the CSF and the external environment (for example, with penetrating trauma to the skull, neurosurgical interventions, meningomyelocele, fistula).

Pathophysiology of acute bacterial meningitis

Under the action of the surface components of the bacterial cell, complement and pro-inflammatory cytokines (tumor necrosis factor, IL-1), neutrophils rush into the liquor-containing spaces. Neutrophils produce membrane-toxic metabolites that damage the endothelium of the vessels, resulting in vasculitis and thrombophlebitis leading to focal ischemia or infarction and edema of the brain. As a result of vasculitis, the integrity of the blood-brain barrier is violated, which contributes to the further increase of brain edema. Purulent exudate in cerebrospinal fluid blocks circulation and reabsorption of the cerebrospinal fluid, resulting in the development of hydrocephalus. Increasing cerebral edema and hydrocephalus further increase intracranial pressure, systemic complications develop, including hyponatremia due to the syndrome of inadequate synthesis of antidiuretic hormone (SNADH), disseminated intravascular coagulation (DVS) and septic shock, which often develop bilateral hemorrhagic infarction of the adrenal glands (syndrome Waterhouse-Frideriksen).

Symptoms of acute bacterial meningitis

The occurrence of fever, headache, rigidity of the neck muscles and vomiting, characteristic of meningitis, are often preceded by the symptoms of respiratory diseases. An extremely serious condition can develop in adults within 24 hours, and in children - even faster. Symptoms of Kernig and Brudzinsky appear in about 1/2 patients, in 30% of patients develop epileptic seizures, 10-20% have symptoms of cranial nerve [eg, III (oculomotor nerve), VII (facial nerve), or VIII pair of cranial nerves] and other variants of focal neurologic symptoms. In children older than 2 years and adults, impaired consciousness develops in this order: excitation - deafness - drowsiness - sopor - coma. Opisthotonus may develop.

Dehydration is often observed, with a vascular collapse that can be replaced by shock. For infection, especially meningococcal, is characterized by dissemination throughout the body with penetration into the joints, lungs, sinuses and other organs. The appearance of a petechial (hemorrhagic) or purple rash indicates generalized septicemia and meningococcal meningitis. With a close examination of the head, ears, spine and skin, it is possible to identify the source or entrance gates of the infection. Deepening in the spine, fistula, nevus or hair bundles may indicate the presence of meningomyelocele.

In children younger than 2 years, meningeal signs may be absent. In children of the first two months of life, the clinical symptoms of meningitis are non-specific, especially in the early stages of the disease. Often there are fever, hypothermia, dystrophy, drowsiness, vomiting and irritability. Later, epileptic seizures, piercing screaming, bulging and tension of the large fontanel can join. A few days later, young children can develop a subdural effusion, manifested by epileptic seizures, constant fever and hydrocephalus.

In elderly people, symptoms can also be nonspecific (eg, inhibition with or without fever), meningeal signs may be absent or minor. In this case, the limitation of movements in the neck (all directions) in them can be due to arthritis, which should not be mistaken for manifestations of meningism.

Partially treated meningitis. When a patient has an average otitis or sinusitis in the early stage of the disease, antibiotics are usually prescribed before the appearance of typical signs of meningitis. Some drugs can partially (but temporarily) suppress the infectious process, which will manifest slow progression of the disease, weakening of meningeal symptoms. This situation significantly complicates the diagnosis of meningitis.

Diagnosis of acute bacterial meningitis

Fever, blockage or irritability, piercing screaming, bulging of the parietal fontanel, meningeal signs or hypothermia in children under 2 years of age are grounds for suspecting acute bacterial meningitis. Likewise, in older children and adults, bacterial meningitis should be thought of if they have meningeal symptoms, impaired consciousness of an unclear genesis, especially if there is fever and risk factors.

Because acute bacterial meningitis, especially meningococcal, can lead to death within a few hours, it requires emergency diagnosis and treatment. Emergency lumbar puncture and treatment with antibiotics and glucocorticoids are indicated, without waiting for the results of laboratory tests.

CSF pressure can be increased. In Gram-smeared smears, microorganisms in the CSF are determined in 80% of patients. The number of neutrophils in CSF usually exceeds 2000 / μL. The concentration of glucose is reduced to less than 40 mg / dL due to disrupted transport of glucose to the central nervous system and its absorption by neutrophils and bacteria. The protein level is usually more than 100 mg / dL. The results of sowing are positive in 90% of cases; in partially treated, they can be false-negative. To identify meningococcal antigens Haemophilus influenzae type B, pneumococcus, streptococcus Group B strain and Kl E . coli, the latex agglutination reaction is used. With the help of the lysate of amoebocytes of the horseshoe, the presence of gram-negative bacteria in the blood of endotoxin is revealed (LAL-test). LAL test and latex agglutination reaction help to identify pathogens in cases of partially treated meningitis and meningitis against the background of immunodeficiency, and also in cases when the pathogen is not isolated from the CSF. PCR helps to establish a pathogen in similar situations.

The CT picture is either normal, or shows a decrease in ventricular size, smoothing of the furrows and an increase in density over the convective surfaces of the hemispheres. MRI with gadolinium is the best method for diagnosing subarachnoid inflammation. Obtained images should be carefully studied to identify signs of brain abscess, infection of the paranasal and mastoid processes, fractures of the skull bones and congenital malformations. Later - in a few days or weeks - venous infarcts or communicating hydrocephalus may be detected.

A number of infectious and non-infectious diseases can resemble bacterial meningitis, the clinical picture of the disease, in combination with the results of CT and CSF analysis, helps differentiate them. Despite the fever, headache and rigidity of the neck muscles, viral meningitis, however, is much easier with other changes in the cerebrospinal fluid. A violent and sudden onset of the disease, severe headache and rigidity of the neck muscles are also characteristic for subarachnoid hemorrhage, but there is no fever, CT is diagnosed with hemorrhage, the CSF contains a large number of erythrocytes or has a xanthrome coloration. Brain abscess is accompanied by an increase in body temperature, headache and impaired consciousness, but the rigidity of the neck muscles is not characteristic, unless the contents of the abscess breaks into the liquor-containing space with the lightning development of secondary meningitis. Severe generalized infectious diseases (for example, sepsis, infective endocarditis) can occur with a violation of consciousness, increased body temperature, a decrease in tissue perfusion, but there is no stiff neck, and CSF, either without pathological changes or with a slight leukocytosis. The wedging of the cerebellar tonsils can cause a secondary impairment of consciousness (due to obstructive hydrocephalus) and rigidity of the neck muscles, but there is no fever, and the true cause is easily diagnosed by CT or MRI. Moderate fever and headache, changes in mental status and inflammation of the brain membranes are observed with cerebral vasculitis (for example, lupus) and venous thrombosis, however, the changes in cerebrospinal fluid in these diseases are similar to those in viral encephalitis.

The acute onset of the disease, the lightning course, clinical manifestations and results of CSF studies in fungal meningitis or amoebic (Naegleria) meningoencephalitis are virtually indistinguishable from the pattern of bacterial meningitis. When Gram stains and standard crops, bacteria are not detected. Investigation of cerebrospinal fluid under a microscope and sowing on selective nutrient media allows to detect a fungus. Characteristic movements of amoebae can be seen in the study of a noncentrifugated CSF by the method of a thick drop; In addition, they are sowing on selective media. For tuberculous meningitis, a subacute or chronic course is typical with rare exceptions; by the nature of changes CSF in tuberculosis takes an intermediate place between acute bacterial and aseptic meningitis; To confirm the diagnosis, use special methods of staining (for acid-fast bacteria or immunofluorescent).

Blood tests include sowing (positive blood culture is obtained in 50% of cases), a general clinical blood test with a leukocyte formula, a biochemical blood test (electrolytes, serum glucose, residual nitrogen and urea), and a coagulogram. Monitoring of Na content in the blood plasma is carried out in order to identify SNAP, monitoring the parameters of the coagulogram allows not to miss the onset of the development of ICE. Urine culture, discharge from the nasopharynx, secretion of the respiratory tract and discharge from the lesions on the skin are carried out.

Waterhouse-Friderixen syndrome can be suspected in cases when a patient with a high fever does not come out of a shock state, despite adequate treatment, or when a patient suddenly has a hemorrhagic rash and signs of an ICE syndrome. Determine the level of cortisol and conduct CT, MRI or ultrasound of the adrenal glands.

[7], [8], [9], [10], [11],

Prognosis and treatment of acute bacterial meningitis

Antibacterial and symptomatic therapy for early detection of the disease allowed to reduce the lethality in acute bacterial meningitis to below 10%. However, with late diagnosis, in newborns, seniors and people with immunodeficiency, lethality remains high. The prognosis is unfavorable with persistent leukopenia or the development of the Waterhouse-Frideriksen syndrome. The survivors may experience deafness and symptoms of injury to other cranial nerves, cerebral infarction, repeated convulsive seizures and mental disorders.

When suspected of acute bacterial meningitis, treatment with antibiotics and glucocorticoids begins immediately after taking blood samples and CSF for sowing. In less severe cases and doubt in the diagnosis, the appointment of antibiotics can be postponed until the CSF analysis results are obtained. The onset of antibiotic therapy before performing lumbar puncture increases the probability of obtaining false negative results of bacteriological examination, especially in the case of pneumococcal infection, but does not affect the results of the remaining studies.

Dexamethasone in a dose of 0.15 mg / kg for children and 10 mg for an intravenous adult every 6 hours should be started 15 minutes before the first dose of antibiotics and continue for 4 days. Dexamethasone can prevent hearing loss and other neurological complications by suppressing the release of pro-inflammatory cytokines released by bacterial lysis under the action of antibiotics. Dexamethasone should not be prescribed to patients with immunodeficiency, so as not to disrupt immune protection in aseptic meningitis. If the causative agent from CSF is not isolated, it is advisable to supplement the treatment with antituberculous drugs. If the crop does not give growth or the culture was identified after 24-48 h, the administration of glucocorticoids should be discontinued; the administration of glucocorticoids over 24 hours without adequate antibiotic cover can exacerbate the infectious process. In addition, glucocorticoids prevent the penetration of vancomycin through the blood-brain barrier, therefore, the dose of vancomycin should be increased.

If there are doubts about the correctness of the CSF analysis results, the lumbar puncture can be repeated after 8-24 hours (or earlier, if the patient's condition worsens). If the clinical picture and the final results of CSF analysis confirm the diagnosis of aseptic meningitis, antibiotics should be discontinued. If the state of the patient remains severe against the background of antibiotic therapy (possibly, which has become the cause of the false negative result of inoculation), the administration of antibiotics does not stop.

The choice of antibiotic depends on the type of pathogen and the age of the patient. Cephalosporins of the third generation (for example, ceftriaxone, cefotaxime), as a rule, are universally effective against most pathogens isolated from patients of all age groups. Instead of cephalosporins of the 3rd generation, children can be prescribed cephalosporin of the 4th generation cefepime; In addition, cefepime is indicated for meningitis of Pseudomonas aeruginosa. Currently, in connection with the spreading resistance of pneumococci to cephalosporins, they are trying to replace vancomycin in combination with rifampin (or without). Ampicillin retained its effectiveness against listeria. Although aminoglycosides poorly penetrate the blood-brain barrier, they are still used for the empirical treatment of gram-negative meningitis in newborns. After clarifying the etiology of the disease, according to the results of a bacteriological study, antibiotic therapy is corrected.

After antibiotic therapy is started, a continuous control of the cerebrospinal fluid for sterility and cytosis is carried out every 24-48 hours. Antibiotics continue to be administered for at least one week after normalizing the body temperature and improving the CSF parameters almost to the norm (full normalization may take several weeks). Dosages of antibiotics do not decrease after clinical improvement, because as the inflammatory process in the membranes decays, their permeability decreases.

Doses of intravenous antibiotics for bacterial meningitis

	Dosage
Antibiotic	Children	Adults
Ceftriaxone	50 mg / kg h / h 12 h	2 grams / h 12 h
Cefotaxime	50 mg / kg	2 g / h 4-6 h
Ceftazidime	50 mg / kg b / w 8 h	2 g h / h 8 h
Cefepim	2 hrs 12 h	2g / s8-12h
Ampicillin	75 mg / kg	2-3 g hour 4 h
Penicillin G	4 million units h / h 4 h	4 million units h / h 4h
Nafcillin and oxacillin	50 mg / kg	2 g hour 4 h
Vancomycin	15 mg / kg	500-750 mg h / h 6 h
Gentamicin and tobramycin	2.5 mg / kg	2 mg / kg b / w 8 h
Amikacin	10 mg / kg	7.5 mg / kg h / h 12 h
Rifampin	6.7 mg / kg	600 mg h / h 24 h
Chloramphenicol	25 mg / kg	1 g hour 6 h

The kidney function should be monitored.

Symptomatic therapy is aimed at normalizing body temperature, cupping of the edema, correction of electrolyte disorders, seizures and shock. If suspicion of Waterhouse-Friderixen syndrome is prescribed high doses of hydrocortisone (from 100 to 200 mg intravenously every 4 hours or as a continuous infusion after the initial bolus injection); the lack of data on the concentration of the hormone in the blood is not a reason for delaying treatment.

With a strong cerebral edema, the amount of fluid administered is monitored, and controlled hyperventilation (PaCO ₂, 25-30 mmHg), mannitol (0.25-1.0 g / kg w / w) is prescribed to prevent central and transstan- and dexamethasone (4 mg IV every 4 hours); monitor intracranial pressure. With increasing ventricular size, monitoring of intracranial pressure is connected and ventricles are drained in order to eliminate excess CSF, but the prognosis is usually unfavorable.

In young children in the presence of subdural effusions, it is necessary to remove fluid by repeated daily subdural punctures through the seams of the skull. Number outputted from each side liquor not be greater than 20 ml / day in order to avoid bias medulla. If the effusion, despite punctures, persists for 3-4 weeks, surgery is shown with the possible excision of the subdural membrane.

In the case of severe meningococcal meningitis, it is advisable to administer drotrekogin alpha (activated protein C) to effectively suppress the inflammatory response. With the development of sepsis against the background of meningitis, the risk of intracranial hemorrhages increases dramatically, regardless of whether the patient receives the Droscogene or not.

Prevention of acute bacterial meningitis

All children are recommended the introduction of a conjugated 7-valent pneumococcal vaccine, covering more than 80% of microorganisms-pathogens of meningitis. A standard high-performance anti-hemophilic vaccine is administered at the age of two months. A tetravalent meningococcal vaccine is administered to children with immunodeficiency or functional asplenia at the age of 2 years; In addition, travelers traveling to endemic areas are vaccinated, and laboratory medical personnel directly in contact with samples of meningococcal infection in daily practice. It is advisable to cover the immunization of the meningococcal vaccine of students living in hostels and conscripts into the armed forces.

To limit the airborne transmission of the patient, meningitis is placed in a special box with respiratory isolation for at least the first 24 hours. Gloves, masks and medical gowns are used. Among the family members of the patient, medical personnel and others who were in close contact with the patient, it is necessary to conduct post-exposure prophylaxis. In the case of meningococcal meningitis, it consists in immunizing the meningococcal vaccine (to prevent spread) and taking rifampicin inside within 48 hours (for adults, 600 mg twice a day, for children 10 mg / kg 2 times / day, for newborns 5 mg / kg 2 times / day). As an alternative, single intramuscular administration of ceftriaxone is allowed (adults - 250 mg, children - 125 mg) or a single dose of 500 mg ciprofloxacin inside (adults only). To prevent hemophilia, rifampicin is taken at a dose of 20 mg / kg orally once a day (but not more than 600 mg / day) for 4 days. Concerning the conduct of postcontact prophylactic measures for young children (up to 2 years) in kindergartens and nurseries there is no unanimity. After contact with pneumococcal infection, chemoprophylaxis is usually not carried out.