PURULENT MENINGITIS IN CHILDREN

Main Statements

Causative agents of meningitis can be bacteria, viruses and fungi. Main clinical presentation of meningitis is meningeal syndrome. The most common causes of purulent meningitis in children are meningococci,

pneumococci and Haemophylus influenza. The most common causes of serous meningitis in children are enteroviruses and

mumps virus. All the patients with purulent meningitis, regardless of clinical presentation and disease

severity, must be obligatory hospitalized to specialized infectious department. Main method of treatment of purulent meningitis is antibiotic therapy. Main method of prophylaxis of purulent meningitis (meningococcal, pneumococcal

and haemophylic) is vaccination.

Meningitis is an acute infectious inflammatory disease of brain and spinal

meninges.

Main causative agents of purulent meningitis in children:

- Meningococcus;

- Pneumococcus;

- Haemophylus influenza type B;

-Staphylococcus;

- Streptococcus;

- Escherichia;

- Salmonella;

- Proteus;

- Klebsiella;

- Pseudomonas aeruginosa;

- Listeria;

- Enterococcus.

Clinical manifestations.

Purulent meningitis usually begins acutely with fever till 390-400С, chills and

headache. Headache is often accompanied by dizziness. First year of age children

utter screams, are considerably agitated. Restlessness in majority of cases changes

into flaccidness. All the symptoms of meningeal syndrome are prominent.

Newborns and children of the first months of life who develop meningitis can

present with toxicosis signs, decreased consciousness, clonic and tonic seizures

with the absence of meningeal symptoms.

Other neurological symptoms at purulent meningitis include transitory or

permanent cranial nerves paralyses, vestibular abnormalities. Part of children can

develop soporous or comatose state. All the above mentioned signs are more

typical for pneumococcal meningitis and the one caused by Haemophylus

influenza type B.

Seizures develop quite often at purulent meningitis. Patients with

haemophylic or pneumococcal meningitis develop seizures twice as often as

patients with meningococcal meningitis. Appearance of seizures during the first

days of the disease does not have particular prognostic value, whereas seizures

after the 4th day of the disease require special attention. The latter can be associated

with consequences and complications of bacterial meningitis.

Besides neurological symptoms, at purulent meningitis arthralgias and

myalgias can develop, which reflect systemic character of infectious process.

Arthritis development is typical for meningococcal meningitis and it always has

transitory character. Patients with meningitis and presence of bacteremia can

develop infectious toxic shock. In these cases, as a rule, intravascular disseminated

coagulation syndrome develops which is accompanied by prominent arterial

hypotension. In patients with meningococcal infection meningitis can be

accompanied by hemorrhagic purpura. Myocarditis and pericarditis can develop.

Clinical presentation of purulent meningitis depending on etiology.

Meningococcal meningitis is one of clinical forms of meningococcal

infection which can be seen as an isolated form or in combination with other signs

of the disease: nasopharyngitis, meningococcemia, arthritis, pneumonia, etc. It

comprises 60-70 % of all cases of purulent meningitis in children older than 1 year

of age.

Epidemiologically meningococcal meningitis has the signs typical for

respiratory tract infection: periodic morbidity increase, seasonal pattern. Periodic

increases of morbidity are observed every 10-15 years. The cause of these

increases is diminishing of population immunity and changes of antigenic structure

of causative agent. Lately in Ukraine predominant circulation of serogroup B

meningococcus is observed.

Meningococcal infection typically has seasonal pattern with increased

morbidity in winter and spring; disease peak is observed in February-April. In

between-epidemic period predominantly early age children are affected with

meningococcal meningitis (till 80 %), whereas during epidemics the percentage of

older children and adults is increased.

The disease begins acutely, suddenly, with acute temperature increase till 390-

400С and higher. Parents can point out not only the day but also the time of disease

onset. Some patients show symptoms of acute respiratory illness several days

before development of meningitis. Patients complain on severe headache, more

often diffuse, but can also be localized in forehead or occiput. Dizziness is often

seen. Repeated vomiting is typical; it is not connected to meals and do not bring

release. Disease onset in infants can be gradual.

In majority of children increased sensitivity to all kinds of stimuli is seen:

photophobia, severe hyperesthesia, hyperacusia.

As a rule, from the first days of the disease consciousness can be decreased.

At the beginning of the disease agitation can be seen, which later changes to

flaccidity and stupor. Degree of decreased consciousness can increase up till coma.

One of early symptoms of meningococcal meningitis, especially in early age

children, is seizures. They are more often clinic-tonic and prone to recurrence. In

some patients seizures from the very beginning can be similar to epileptic status.

Usually on the 1-2nd day of the disease meningeal signs appear and rapidly

increase: neck stiffness, Kernig’s and Brudzinski symptoms. In early age children

the diagnostic value belongs to symptom of suspension (Lessage), kissing of the

knee, etc. Main meningeal sign in infants is permanent fontanel bulging and

tension. However, at severe intoxication and dehydration children can present with

fontanel sinking down.

Throwing back of the head plays an important role in diagnosis of meningitis

in infants. Typical meningeal posture appears later. The patients lay down on the

side with thrown back head and bended knees, adducted to sunken abdomen.

Focal signs of nervous system damage at meningococcal meningitis are

seldom seen. Most often involvement of VІІІ, rarer ІІІ, VІ and VІІ pairs of cranial

nerves is observed.

On the 3-4th day of the disease many children develop herpetic rash on

different areas of the skin, oral mucosa and lips. Sometimes the rash can be

abundant and can considerably worsen the condition of the child. Some authors

consider appearance of this rash a specific sign of meningococcal meningitis.

However, herpetic rash is also often seen at meningitis of other etiology and at

severe forms of other infectious diseases.

Cerebro-spinal fluid at first hours of the disease can be opalescent and can

show neutrophilic-lymphocytic cytosis, normal protein level and positive globulin

reactions. With disease course the CSF becomes cloudy, cytosis is increased till

thousands and tens of thousands of neutrophils in 1 mcl, the level of protein in

increased. Sometimes decreased glucose and chlorides level is seen, which predicts

disease severity and possible prolonged course.

Meningococcal meningitis is seldom seen in newborns. However, if there are

carriers of meningococcus among maternity house personnel or departments of

neonatal pathology, outbreaks of meningococcal infection can develop. In case of

meningococcal infection in a pregnant woman, intrauterine fetal infection can

develop.

Clinical course of meningococcal meningitis often depends on terms of

diagnosis and adequate therapy. If the diagnosis is made timely, that is, on the 1-2nd

days of the disease, and therapy is adequate, in majority of cases disease outcome

is favorable. Clinical signs of the disease disappear on the 5-6th days of the disease;

CSF clearance occurs in the 8-10th day.

Pneumococcal meningitis

According to frequency, pneumococcal meningitis possesses the second place

after meningococcal meningitis. The frequency of the latter is 12-16 % among all

purulent meningitis. Pneumococcal meningitis presents with severe course and

high mortality which reaches 40-60%. Children of the first years of life are

predominantly affected, more often from 6 months till 1 year of life, but the

disease is also possible in older children and adults.

Pneumococcal meningitis is more often registered as a sporadic disease but

sometimes outbreaks are seen. Development of the disease in 60-70 % of cases is

preceded by presence of purulent focus of infection. Most often it can be otitis,

sinusitis or pneumonia. The facilitating factor of meningitis development is head

trauma. In children with head trauma in the past, even long-term ago, acute and

chronic diseases of upper respiratory tract can lead to development of meningitis.

The disease onset is acute in majority of cases. Fever is till 380 – 390 С, severe

headache, hyperesthesia and repeated vomiting develop. Meningeal symptoms

appear early.

Particularity of pneumococcal meningitis is development of brain edema,

which can be the main cause of death during the first 3 days of the disease. At this

complication consciousness decreases and seizures prevail in clinical picture. More

than half of patients develop symptoms of cranial nerves damage (ІІІ, VІ, VІІ, ІX,

X pairs). In some patients pareses of extremities and hyperkinesias are seen.

Clinical signs of brain edema are more prominent than meningeal signs, especially

in early age children. In some cases it can be the reason for diagnostic mistakes.

Brain edema can also develop later in the disease course. In some cases the disease

presents with syndrome of ependymitis.

In patients with septic course of the disease appearance of hemorrhagic rash

similar to that at meningococcemia is possible. At this form pneumonia,

endocarditis and arthritis can be seen.

Cerebral spinal fluid at pneumococcal meningitis is always cloudy, of

greenish-grayish color. Neutrophilic cytosis reaches from several hundreds till tens

of thousands cells per 1 mcl. Protein level is increased till 3-6 g/l and higher.

Dramatic increase of protein level justifies development of ventriculitis and often

precedes lethal outcome. Especially severe cases are accompanied by high protein

level and low cytosis.

Pneumococcal meningitis often has prolonged or recurrent course. Even at

early treatment onset CSF clearance occurs not earlier than 12-14 th days of the

disease. Late onset of therapy with delay for 3-4 days can lead to prolonged disease

course due to consolidation of purulent-fibrinous exudates. Prolonged course of

meningitis is often accompanied by complications and persistent residuals.

Haemophylic meningitis

Haemophylus іnfluenzae has several serotypes (a, b, c, d, e, f), from which the

serotype b (Hіb) is the most common infectious agent, causing generalized forms

of the disease. Hіb is the leading cause of purulent meningitis in early age

children. In Ukraine the frequency of meningitis caused by Hіb, according to

different authors, is from 3 till 9 % among all purulent meningitis in children.

Recently the disease frequency growth is observed which can possibly be

explained by improvement of laboratory diagnosis.

Haemophylic meningitis most commonly develops in early age children.

Majority of children have unfavorable premorbid conditions: complicated

pregnancy and delivery in mother, perinatal pathology of the child. Among these

children there are a lot of prematurely born and malnourished children. These

children often develop respiratory diseases, otitis, pneumonia. Haemophylic

meningitis most commonly develops concurrently with bronchitis, pneumonia and

otitis.

Haemophylic meningitis often has subacute course with gradual onset, but

sometimes the disease begins acutely. Along with moderate fever (37.50-380С),

sleepiness, adynamia, vomiting and slowly increasing intoxication are seen.

Meningeal signs are not prominent.

At septicemia caused by Hіb hemorrhagic rash on the skin and joint and lung

involvement can appear. Development of infectious toxic shock is possible.

The disease often has wave-like course with periods of worsening and

improvement of the patient condition. Moreover, short-term improvement can be

even seen at the absence of appropriate therapy.

Clinical presentation of meningitis can often be disguised by pneumonia

symptoms or by gastrointestinal disturbances. Development of dehydration is

typical. In these cases the tissue turgor is decreased, facial features are pointed,

intracranial hypotension develops with sinking down of large fontanel. Meningeal

signs are not seen; muscle hypotonia and hyporeflexia develop. It is very difficult

to suspect meningitis in these patients.

Cerebral spinal fluid at haemophylic meningitis often is leaking by rare drops.

Cytosis can be from several hundreds till tens of thousands cells per 1 mcl. CSF

reveals predominant neutrophils, but at the first days of the disease number of

lymphocytes can be increased. Protein level is increased till 1 g/l.

Mortality at haemophylic meningitis according to different authors is from 4

till 30 %. Frequency of residuals reaches 20-25 %. Before introduction of anti-

haemophylic vaccination into medical practice, haemophylic meningitis was one of

the main causes of mental retardation and deafness in children. In some patients

residuals develop which include hydrocephalic syndrome and cerebellum-

pyramidal disturbances.

Diagnosis. Clinical criteria:

1. General infectious syndrome:

increased body temperature;

agitation which rapidly changes into flaccidness, sopor, in severe cases into

coma;

muscle tonus is decreased, tendon reflexes are increased; anisoreflexia is

seen, in severe cases reflexes are inhibited;

pathological reflexes (Babinski, Rossolimo, etc.), feet clonus;

anisocoria;

possible clonic and tonic seizures;

possible impairment of cranial nerves, more often ІІІ, ІV, VІ, VІІ, VІІІ

pairs;

possible development of infectious toxic shock;

head trauma in the past.

2. Meningeal syndrome:

hydrocephalic-hypertension symptoms: severe diffuse headache, repeated

vomiting, general, auditory and acusitory hyperesthesia;

meningeal signs: “meningeal” posture, tonic tension of back muscles, neck

stiffness, positive symptoms of Kernig and Brudsinski (upper, medial and

lower).

Diagnosis of meningitis in first month of age children: newborns can be

suspected for meningitis if they present with two of the listed symptoms:

temperature instability (hypо- or hyperthermia), possibly normal body

temperature;

changes of child’s behavior (depression or agitation);

loud (high-pitched) cry;

feeding refusal, regurgitations, vomiting;

appearance of seizures, hyperkineses, hand tremor and nystagmus;

fontanel bulging or tension, widening of fissures;

anisocoria;

throwing back of the head;

positive Lessage symptom;

decreased consciousness;

appearance of any pathological neurological symptom with respiratory

distress-syndrome, pneumonia, otitis, sinusitis, other infectious disease.

Diagnosis of meningitis in children from 1 till 18 months of age:

Suspected case of bacterial meningitis in a child from 1 till 18 months of age

can be a disease with acute onset, fever (higher than 380С in axillary area) and

presence of one of the following symptoms:

neck stiffness and throwing back of the head;

fontanel bulging or tension;

hyperesthesia;

monotonous high-pitch cry;

not motivated changes of behavior;

inactive suckling, feeding refusal;

vomiting;

consciousness decrease;

clonic and tonic seizures;

extremities tremor;

eyes movement disturbances;

anisocoria;

presence of any focal neurological symptoms;

meningeal signs, positive Lessage symptom.

Paraclinical investigations:

1. Complete blood count reveals neutrophilic leukocytosis with young

forms, accelerated ESR.

2. CSF analysis shows neutrophilic cytosis, increased protein level. In

severe cases decreased glucose level.

3. Performance of lumbar puncture can be preceded by: clinical

examination, oculist consulting (with examination of eye fundus), if required

– consulting of ENT, neurologist, neurosurgeon, hematologist, as well as

complete blood count and urinalysis.

4. Bacterioscopic SCF examination and blood smears with Gram staining;

5. Bacteriological culture on selective nutritional media of CSF, blood,

nasopharyngeal mucus;

6. Serological methods (reaction of latex agglutination, countercurrent

immunoelectrophoresis, immune enzyme analysis).

7. Detection of bacterial nucleic acids in CSF by PCR method.

Treatment of purulent meningitis. All the patients with purulent

meningitis, regardless of clinical form and severity of the disease must be

obligatory hospitalized into specific infectious departments. The child should be

places on its side during the first day of hospitalization to prevent aspiration.

Children with signs of intracranial hypertension (ICH) and brain edema (BE)

must be hospitalized into intensive care units. At the presence of signs of ICH

and/or BE the head end of the bed should be elevated on 300. The child should be

rotated every 2 hours to prevent bedsores.

Condition monitoring in the hospital is performed by nurse during the first

day of hospitalization every 3 hours, later every 6 hours. The doctor evaluates

child’s condition twice a day and more often if required.

Antibacterial therapy. Empiric antibacterial therapy.

Empiric choice of antibiotic at meningitis is used in the conditions when

etiology is not confirmed during the first day of hospitalization, performance of

lumbar puncture is delayed or CSF Gram stains are not informative.

Antibiotics recommended for empiric therapy of purulent meningitisPatients age Most possible etiology Recommended antibiotic

From 0 till 4 weeks

Str. agalactiae, E. coli,K. pneumoniae, St. aureusL. monocytogenes,

Ampicillin + cefotaxime ± aminoglycoside

From 4 weeks till 3 months H. influenzae,S. pneumoniae,N. meningitidis

Ampicillin + 3rd generation cephalosporin (cefotaxime, ceftriaxone)

From 4 months till 18 years N. meningitidіs, S. pneumoniae,H. influenzae

3rd generation cephalosporin (cefotaxime, ceftriaxone) or penicillin G

With head trauma, neurosurgery or cerebrospinal shunting, nosocomial and otogenic meningitis

St. aureus Str. pneumoniaeEnterococcus Pseudomonas aeruginosa

Vancomycin + ceftazidime

Length of antimicrobial therapy of purulent meningitis in children

Causative agent Recommended length of antibacterial therapy in days

N. meningitidіs 7H. influenzae 10-14

Str. pneumoniae 10-14Str. аgalactiae 14L. monocytogenes 21Enterobacteriaceae 21St. аureus, St. еpidermidis,Enterococcus

28

Pseudomonas aeruginosa 28

Etiotropic therapy of purulent meningitis considering the detected causative

agent. After investigation of CSF culture, antibacterial therapy is prescribed with

consideration of specific causative agent, its sensitivity or resistance to antibiotics.

At relapses of purulent meningitis reserve antibiotics are given.

Additional therapy. Indication for dexamethasone prescription at purulent

meningitis in children:

1. Meningitis in children from 1 to 2 months of age. Newborns with meningitis

are not given dexamethasone.

2. Children with Gram-negative bacteria in CSF smear.

3. Patients with high intracranial pressure.

4. Patients with brain edema.

Dexamethasone is given in dosage 0.15 mg/kg every 6 hours during 2-4 days.

The drug is injected 15-20 minutes before first dosage of antibiotic or 1 hour after.

Infusion therapy. Starting solutions at purulent meningitis should be 5%-

10% glucose solution (with potassium chloride, 20-40 mmol/l) and normal saline

in correlation 1:1. In first year of age children this correlation is 3:1.

Colloid solutions as starting ones are used at increased intracranial

pressure and brain edema in combination with hypovolemia and arterial

hypotension.

Amount of intravenous infusion per day is 30-50 ml/kg of body weight and

should not exceed diuresis. Total fluid volume (intravenous and per mouth) during

the first day is calculated considering physiological requirement. With positive

dynamics one-time infusing during 6-8 hours is admissible.

At the presence of signs of increased intracranial pressure and brain edema

infusion therapy is directed to regulation of the volume and optimization of brain

microcirculation, which is maintained by isovolemia, isoosmolarity and

isooncoticity.

Standard supportive infusion is performed with 5%-10% glucose solution

(with potassium chloride solution of 20-40 mmol/l) and physiological solution of

normal saline in correlation 1:1. In first year of age children this correlation is 3:1.

Since the second day the infusion therapy is performed with the goal of

support of null water balance, at which the amount of excreted urine must not be

less than the amount of intravenous fluid and not less than 75% from total daily

amount of injected fluid.

Treatment of children with purulent meningitis accompanied by infectious

toxic shock is performed according to protocol of meningococcemia treatment.

Prophylaxis of meningitis. For prophylaxis of purulent meningitis in

children vaccination is used. Currently there are simple polysaccharide and

conjugated vaccines against meningococcus, pneumococcus and Haemophylus.

According to vaccination schedule in Ukraine, obligatory is the vaccine against

Haemophylus influenza, which is performed at the age of 3-4 and 18 months.

Vaccination against meningococcal and pneumococcal infections in Ukraine is

recommended.

Questions for self-control

1. Give the definition of “meningitis” term.2. Etiological particularities of purulent and serous (aseptic) meningitis in children.3. Clinical signs of serous and purulent meningitis in children depending on etiological factor.4. Particularities of clinics and diagnosis of meningitis in first year of age children.5. Laboratory diagnosis of meningitis, modern methods of investigation.6. Differential diagnosis of meningitis according to CSF character (purulent and serous meningitis).7. Differential diagnosis of serous and purulent meningitis in children.8. Antibiotics recommended for therapy of purulent meningitis.9. Spectrum of antibiotics for treatment of purulent meningitis depending on age and etiology.10.Pathogenetic therapy of meningitis in children.

Tests for self-control

1. The most common cause of purulent meningitis in children:А. Meningococcus

В. Proteus С. Staphylococcus D. Pseudomonas aeruginosa Е. Listeria 2. The most common causes of serous meningitis:А. Mycoplasma В. Enteroviruses С. FungiD. ProtozoaЕ. Meningococcus 3. Main route of bacteria penetration into central nervous system:А. Hematogenous В. Contact С. Transneural D. Alimentary Е. Sexual 4. At purulent and serous meningitis are predominantly affected:А. Dura mater and arachnoid membraneВ. Pia materС. Only arachnoid membrane D. Pia mater and dura mater Е. No correct answer 5. Leading clinical syndromes at purulent meningitis in children are:А. Meningeal В. CSF changes С. Seizures D. Total cerebral Е. All the answers are correct 6. For the clinics of meningococcal meningitis in first year of age children it is not typical:А. High fever during the first hours of the disease В. Meningeal posture С. Absence of meningeal signs D. Positive Lessage symptom, large fontanel bulging Е. Abundant hemorrhagic rash on the skin 7. Early appearance and rapid regression of focal symptoms at purulent meningitis are due to:А. Hemorrhage into brain parenchyma В. Encephalitis С. Transitory blood and CSF circulation disturbancesD. Brain edema Е. All the answers are correct8. For etiology confirmation of purulent meningitis the causative agent should be isolated from:А. Blood В. Nasopharynx С. CSFD. UrineЕ. Stool9. 3 years old child develops fever till 390С, sleepiness, agitation, vomiting. The child received 10 days course of ampicillin due to exacerbation of recurrent otitis. At examination: CSF is purulent, Gram-positive diplococcic in the smear. The most adequate therapy is:

А. Ampicillin В. Cefuroxime С. PenicillinD. Ceftriaxone Е. Chloramphenicol 10. The main criteria of antibiotic therapy termination at meningococcal meningitis is:А. Normal body temperature В. Normal CBC С. Absence of meningeal signs D. CSF clearance Е. All the answers are correct

Test answers

1-A, 2-B, 3-A, 4-B, 5-E, 6-E, 7-C, 8-C, 9-D, 10-Е.