Download central nervous system Infections: Diagnosis and treatment

Infectious Diseases Board Review Manual
Central Nervous System Infections:
Diagnosis and Treatment
Alfredo J. Mena Lora, MD, and Jeremy D. Young, MD, MPH
INTRODUCTION
Infections involving the central nervous system
(CNS) are an important cause of morbidity and
mortality worldwide. The anatomy of the CNS
is complex, and certain physiologic characteristics, such as the blood-brain barrier, play a vital
role both in the pathophysiology and therapeutic
interventions of these conditions. Many pathogens can infect the CNS, including bacteria, viruses, fungi, mycobacteria, and parasites. These
pathogens can cause a variety of infectious syndromes, including meningitis, encephalitis, and
pyogenic abscess formations, among many others. Many of these syndromes can be mimicked
by noninfectious causes such as neoplasms
and rheumatologic diseases, adding levels of
complexity in the approach to these cases. However, the clinical presentation, physical examination, radiographic findings, and epidemiology
can often help narrow the differential diagnosis.
The rapid recognition and management of CNS
infections is often critical to achieving favorable outcomes, particularly for pyogenic bacterial
infections.
In 2009, more than 88,199 cases of meningococcal meningitis were reported in 14 African
countries. With 5352 deaths reported, the 2009
epidemic season was one of the worst recorded.1
Meanwhile, the incidence of meningococcal disease in the United States has been in a steady 20year decline, with less than 1000 cases reported
each year.2 Meningococcal meningitis highlights
facts that pertain to all CNS infections: the risk of a
given pathogen is influenced by vaccination status,
geographic region, epidemiologic exposures, comorbidities, and the immune status of the host. It is
imperative for clinicians to understand the key concepts involving CNS infections in order to promptly
initiate appropriate empiric antimicrobial therapy.
CASE PRESENTATIONS
CASE PATIENT 1
A 64-year-old man with no previous medical history presents to the emergency department (ED)
complaining of headache, which began acutely
and is severe in intensity. The patient also reports
subjective fevers, chills, and a stiff neck. On examination, he is febrile with a temperature of 101.4oF.
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2 Hospital Physician Board Review Manual
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C e n t r a l N e r v o u s S y s t e m I n f e c t i o n s : D i a g n o s i s a n d Tr e a t m e n t
Table 1. Risk Factors, Pathogens, and Empiric Antibiotics for Bacterial Meningitis
Risk Factors
Pathogens
Treatment
Age ≤ 50
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Streptococcus agalactiae
Streptococcus pneumoniae
Listeria monocytogenes
Haemophilus influenzae
Pseudomonas and other gram-negative bacilli
Staphylococcus aureus
Listeria monocytogenes
Streptococcus pneumoniae
Mycobacteria
Fungal pathogens
Ceftriaxone 2 g IV every 12 hr
Vancomycin 25–30mg/kg loading dose then 15–20 mg/kg
every 12 hr
Age > 50
Recent neurosurgery
Immunocompromised
Ampicillin 2 g IV every 4 hr
Ceftriaxone 2 g IV every 12 hr
Vancomycin load then 15–20 mg/kg every 12 hr
Cefepime 2g IV every 8 hr
Vancomycin load then 15–20 mg/kg every 12 hr
Ampicillin 2 g IV every 4 hr
Ceftriaxone 2 g IV every 12 hr
Vancomycin load then 20 mg/kg every 12 hr
IV = intravenously.
The physical exam also reveals photophobia and
nuchal rigidity. The patient has no evidence of
delirium or altered consciousness. No focal neurologic deficits are present.
• What is the appropriate initial approach to
suspected meningitis?
BACTERIAL MENINGITIS
Acute meningitis is clinically defined as a syndrome characterized by the onset of meningeal
symptoms over the course of hours and up to
several days. It can be caused by a variety of
viral, bacterial, and parasitic agents.3 Acute bacterial meningitis is a medical emergency requiring
a prompt diagnosis and empiric treatment. In the
pre-antibiotic era, nearly all cases of bacterial
meningitis led to death.4 Poor outcomes are associated with greater burden of microorganisms
in cerebrospinal fluid (CSF), and therefore the
prompt administration of appropriate antimicrobial agents—with adequate dosing—is one of the
cornerstones of management.5 The proper initial
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empiric regimens vary based on epidemiologic
risk factors (Table 1), with b-lactams playing a key
role in most combinations.3,5 It is common for clinicians to encounter patients who report a history of
allergy to β-lactams, with some estimates suggesting an allergy prevalence of approximately 10% in
the general population.6 Thus, clinicians must also
know how to approach severe infections and lifethreatening conditions with appropriate alternative
therapies, when indicated.
The advent of effective antimicrobials and vaccines for certain pathogens has dramatically decreased the morbidity associated with, and the
incidence of, bacterial meningitis. Potent antimicrobials introduced in the 1930s and 1940s drastically
changed meningitis from an untreatable condition
to one that is potentially curable. Despite the use of
modern therapeutics, the case fatality rate for meningitis remains high, with some studies reporting
rates as high as 25%.7 Effective vaccines against
Streptococcus pneumoniae and Haemophilus influenzae type B dramatically decreased the incidence
of this disease, particularly in the pediatric populaInfectious Diseases Volume 16, Part 1 3