Acute Bacterial Meningitis
Acute Bacterial Meningitis
Acute Bacterial Meningitis
Acute Bacterial
Meningitis
C O N T I N UU M A UD I O
I NT E R V I E W A V AI L A B L E
ONLINE
By Larry E. Davis, MD, FAAN
ABSTRACT
PURPOSE OF REVIEW: While acute bacterial meningitis is becoming less
common in developed countries because of the widespread use of
vaccines against Streptococcus pneumoniae, Neisseria meningitides, and
Haemophilus influenzae, bacterial meningitis still occurs worldwide, with
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Address correspondence to
Dr Larry E. Davis, New Mexico VA
Health Care System, 1501 San
INTRODUCTION
A
Pedro Dr SE, Albuquerque, NM cute bacterial meningitis is a severe life-threatening inflammation
87108, Larry.Davis@VA.gov. of the meninges and subarachnoid space caused by bacteria. The
RELATIONSHIP DISCLOSURE: inflammation can also involve the brain cortex and spinal cord
Dr Davis receives publishing owing to their anatomic proximity. The condition requires
royalties from Springer Science+
immediate medical attention and management. Meningeal
Business Media, LLC.
inflammation causes vasospasm and possible thrombosis of cerebral arterioles
UNLABELED USE OF and arteries as well as possible cerebral vein occlusions. A variety of inflammatory
PRODUCTS/INVESTIGATIONAL
USE DISCLOSURE:
products of bacteria and neutrophils can cross the pial barrier to cause neuronal
Dr Davis reports no disclosure. necrosis or compress cranial nerves. Acute bacterial meningitis occurs
worldwide, develops in individuals of all ages, and causes morbidity and
© 2018 American Academy mortality. In 2013, an estimated 16 million cases of acute bacterial meningitis
of Neurology. occurred.1 This article focuses on the clinical characteristics of acute bacterial
Children
The manifestations of meningitis may develop over hours or up to a day in
children. Classic features include fever, severe headache, lethargy, irritability,
A 4-month-old infant boy was noted by his mother to be fussy and less CASE 1-1
active than usual and was breast-feeding poorly. Soon thereafter, he was
noted to have generalized weakness, so his mother took him to the
pediatrician. The infant’s older sister had reported an earache for several
days. The physician confirmed the symptoms and noted the infant’s
temperature to be slightly elevated but did not detect a stiff neck or
spasticity. He was immediately taken to the emergency department,
where a lumbar puncture was performed. The lumbar puncture showed
a white blood cell count of 350 cells/mm3 with 80% neutrophils, protein
of 280 mg/dL, and glucose of 20 mg/dL (blood glucose was 90 mg/dL).
CSF Gram stain demonstrated gram-positive diplococci. A diagnosis of
acute bacterial meningitis was made, with a suspicion of Streptococcus
pneumoniae. The patient was given IV cefotaxime and dexamethasone
for 14 days and made a full recovery without neurologic sequelae.
This case demonstrates that young infants may not present with typical COMMENT
signs of bacterial meningitis. The change in this infant’s behavior was
recognized by his mother, and she promptly took him to the pediatrician,
who recognized the findings as suspicious for bacterial meningitis. The
patient’s CSF findings were typical for pneumococcal meningitis. He had
not been vaccinated with the pneumococcal meningitis vaccine.
CONTINUUMJOURNAL.COM 1265
confusion, photophobia, nausea, vomiting, stiff neck, and back pain.2 About 20%
of children with acute bacterial meningitis will experience a seizure before
admission to the hospital. Risk factors for acute bacterial meningitis in children
are listed in TABLE 1-2. A medication history should be obtained to exclude recent
antibiotic use that could impede isolation of the bacteria from CSF.
On examination, meningeal irritation usually manifests as neck stiffness,
especially on anterior-posterior flexion of the chin to the chest. The Kernig sign
(painful knee extension after flexing the thigh with the hip and knee at 90-degree
angles) and Brudzinski sign (reactive hip and knee flexion when the neck is
flexed) have limited specificity and sensitivity.10
Adults
Risk factors for acute bacterial meningitis in adults and the elderly are listed in
TABLE 1-3. As in children, the classic clinical features of acute bacterial meningitis
in adults are headache, neck stiffness, fever, and altered mental status. A
prospective nationwide study of 1268 adults with community-acquired bacterial
meningitis in the Netherlands found headache in 83%, neck stiffness in 74%,
fever in 74%, and impairment of consciousness in 71%.11 However, some studies
of adults have found all the classic features were present in as little as 41% of
patients.12 Of note, patients receiving analgesics or corticosteroids may not have
neck stiffness. Occasionally, patients may present with focal neurologic deficits,
and a few may have a petechial rash from either meningococcal or pneumococcal
meningitis. Complications of acute bacterial meningitis include seizures (17%),
ischemic stroke (14% to 25%), hydrocephalus (3% to 5%), subdural empyema
(3%), brain abscess (5%), and venous sinus thrombosis (1%).4
TABLE 1-1 Risk Factors for Acute Bacterial Meningitis in Neonates and Infants
◆ Preterm birth
◆ Low birth weight (<2500 g [5.5 lb])
◆ Chorioamnionitis
◆ Endometritis
◆ Maternal Group B streptococci colonization
◆ Prolonged duration of intrauterine monitoring (>12 hours)
◆ Traumatic delivery
◆ Fetal hypoxia
◆ Galactosemia
◆ Urinary tract abnormalities
◆ Dermal sinus tract of spine
◆ Down syndrome
◆ Congenital heart disease
◆ Poverty, malnutrition
◆ Day care attendance
◆ Asplenia
◆ Primary immunodeficiency
◆ Human immunodeficiency virus (HIV) infection
◆ Sickle cell anemia
◆ Cochlear implant
◆ Central nervous system shunt or CSF leak
◆ Recent or current respiratory tract infection
◆ Recent exposure to case of meningococcal or Haemophilus influenzae meningitis
◆ Penetrating head trauma
◆ Dermal sinus of spine
◆ Recent travel to country with endemic meningococcal disease
◆ Lack of immunizations
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TABLE 1-3 Risk Factors for Acute Bacterial Meningitis in Adults and the Elderly
CONTINUUMJOURNAL.COM 1269
CSF opening pressure 200–500 mm CSF Pressure may be lower if patient is an infant/small
child or very dehydrated or if bacteria species is
atypical.18
White blood cell Usually 1000–3000 white blood cells/mm3 White blood cell count can be lower if patient is
count immunosuppressed or taking steroids or if bacteria
species is atypical. However, only rarely are white
blood cell levels less than 100 white blood cells/mm3.
Glucose Usually <40 mg/dL, often below 25 mg/dL Normal CSF glucose is about two-thirds serum level
concentration but may be falsely low if the patient recently received
IV glucose or has a very high blood glucose level.
Many CSF glucose concentrations in bacterial
meningitis are less than 25 mg/dL.
Gram stain Average positive >75% but depends on Concentrations of bacteria in the CSF in patients with
concentration of bacteria in CSF acute bacterial meningitis range from 103 to 108
colony-forming units (CFU)/mL.18 A positive Gram
stain and visualizing bacteria on a Gram stain are
related to the concentration of bacteria in CSF and
are seen 97% of the time with >105 CFU, 60% with 103 to
105 CFU, and only 25% with <103 CFU. When the Gram
stain is positive, the specificity is higher than 97%.19
Culture positive <75% but depends on bacteria concentration Some strains of bacteria grow poorly on standard
and whether patient previously received culture media, and anaerobic bacteria may not grow
antibiotics at all. Most bacteria in CSF are sterilized when
appropriate antibiotics are given 4 or more hours
before lumbar puncture. However, Neisseria
meningitidis can be sterilized in as little as 30 to
60 minutes. False-positive interpretations can occur
from cell debris on the smear or contamination of
bacteria from the laboratory.
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TABLE 1-5 Risk Factors for Cerebral Herniation Following Lumbar Puncture for
Bacterial Meningitisa
CT = computed tomography.
a
Modified with permission from Joffe AR, J Intensive Care Med.25 © 2007 The Author.
bacterial RNA or DNA, it may be possible for future developments to detect the ● The case fatality rate of
common RNA mutations seen in bacterial drug resistance. pneumococcal meningitis is
Another promising new technology is a self-contained pouch into which fresh 10% to 20% in developed
CSF is introduced. Using PCR technology, the test panel can identify six common countries but much higher
(30% to 40%) in developing
bacterial pathogens, plus several common viruses and Cryptococcus neoformans.32 countries.
Limitations include the need for standard CSF cultures as not all bacteria are
included and the lack of antibiotic sensitivities.
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Antimicrobial Agent Dosing for Infants and Childrenb Dosing for Adultsb
Amikacinc,d 20–30 mg/kg/d (divided every 8 hours) 15 mg/kg/d (divided every 8 hours)
Ampicillin 300–400 mg/kg/d (divided every 6 hours) 12 g/d (divided every 4 hours)
Cefepime 150 mg/kg/d (divided every 8 hours) 6 g/d (divided every 8 hours)
Cefotaxime 200 mg/kg/d (divided every 6–8 hours) 8–12 g/d (divided every 4–6 hours)
(maximum dosage 12 g/d)
Ceftazidime 150 mg/kg/d (divided every 8 hours) 6 g/d (divided every 8 hours)
(maximum dosage 6 g/d)
Ceftriaxone 100 mg/kg/d (divided every 12 hours) 4 g/d (divided every 12 hours)
(maximum dosage 4 g/d)
Ciprofloxacin 30 mg/kg/d (divided every 8–12 hours) 1200 mg/d (divided every 8 hours)
Gentamicinc,d 5–7.5 mg/kg/d (divided every 8 hours) 5 mg/kg/d (divided every 8 hours)
Linezolid Age <12 years 30 mg/kg/d (divided every 8 hours) 1200 mg/d (divided every 12 hours)
(maximum single dosage 600 mg)e
Age ≥12 years 20 mg/kg/d (divided every 12 hours)
(maximum single dosage 600 mg)e
Antimicrobial Agent Dosing for Infants and Childrenb Dosing for Adultsb
Meropenem 120 mg/kg/d (divided every 8 hours) 6 g/d (divided every 8 hours)
(maximum dosage 6 g/d)
Nafcillin 200 mg/kg/d (divided every 6 hours) 9–12 g/d (divided every 4 hours)
Oxacillin 200 mg/kg/d (divided every 6 hours) 9–12 g/d (divided every 4 hours)
Penicillin G 200,000–400,000 U/kg/d (divided every 4–6 hours) 24 million U/d (divided every 4 hours)
(maximum dosage 24 million U/d)
Rifampin 10–20 mg/kg/d (divided every 12–24 hours) 600–900 mg/d (divided every 12 hours)
(maximum dosage 600 mg/d)
Tobramycinc,d 7.5 mg/kg/d (divided every 8 hours) 5 mg/kg/d (divided every 8 hours)
Trimethoprim- 15–20 mg/kg/d (divided every 6 hours) 10–20 mg/kg/d (divided every 6–12 hours)
sulfamethoxazolef
Vancomycing 60 mg/kg/d (divided every 6 hours) 30–45 mg/kg/d (divided every 8–12 hours)
a
Modified with permission from Tunkel AR, et al, Clin Infect Dis.7 © 2017 The Authors.
b
Total daily dose (dosing interval in hours).
c
Need to monitor peak and trough serum concentrations.
d
Aminoglycosides should be based off ideal body weight in obesity.
e
Not to exceed the adult dose.
f
Dosing is based on trimethoprim component.
g
Maintain serum trough concentrations of 15–20 mcg/mL in adult patients who receive intermittent bolus administration.
CONTINUUMJOURNAL.COM 1275
TABLE 1-7 Prophylactic Antibiotic Treatment for Close Contacts of Patients With
Meningococcal Meningitisa
a
Data from van de Beek, et al, Clin Microbiol Infect.4
A 30-year-old woman presented with a fever, bad headache, and CASE 1-2
vomiting. History revealed that she loved fresh soft goat cheese; 2 weeks
before the onset of symptoms, she had purchased some at a rural
roadside stand. The local merchant told her he had obtained the cheese
from a farm that pasteurized the goat milk.
On examination, her temperature was 39°C (102.2°F). She was lethargic
but could give a reasonable history, had a stiff neck, and was nauseated.
Head CT was normal. Lumbar puncture showed an opening pressure of
260 mm CSF, 500 white blood cells/mm3 (predominance of neutrophils),
glucose of 26 mg/dL, protein of 95 mg/dL, and negative Gram stain. CSF
polymerase chain reaction (PCR) tests for herpes simplex virus and
enteroviruses were negative. She was hospitalized and treated with
ampicillin and ceftriaxone. Four days later, her CSF grew Listeria
monocytogenes. She made a full recovery.
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CASE 1-3 A 45-year-old man fell off his motorcycle while riding without a helmet.
He was knocked unconscious for several minutes, and his friends called
an ambulance. In the emergency department, he was confused and had a
bloody nose and pain in the right leg. X-rays showed a compound
depressed skull fracture and a nondisplaced fracture of the right femur.
Brain MRI showed a subarachnoid bleed, depressed skull fracture, and
blood in the right frontal and maxillary sinuses. The patient was
hospitalized and transferred to a regional hospital the following day. At
the local hospital, his mental status had returned to normal and his vital
signs remained normal. At the regional hospital, a neurosurgeon removed
the depressed skull fragments. Ceftriaxone was administered. On the
third hospital day, his temperature was elevated to 38.4°C (101.1°F) and he
became confused, with worsening headache. Several hours later, the
confusion worsened. Repeat brain MRI was unchanged.
A lumbar puncture was performed and was notable for an opening
pressure of 300 mm CSF. CSF showed 300 red blood cells/mm3; white
blood cells were 450 cells/mm3 with 90% neutrophils, glucose level was
20 mg/dL, and protein level was 300 mg/dL. CSF Gram stain showed
numerous gram-positive cocci. He was diagnosed with acute bacterial
meningitis secondary to bacterial entry associated with a skull fracture.
He was started on nafcillin for possible Staphylococcus aureus and
vancomycin for methicillin-resistant S. aureus (MRSA). Bacterial cultures
grew MRSA. He survived but had neurologic sequelae.
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