Infectious Diseases in Critical Care Medicine

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Radiologic Tests
Neuroimaging tests are primarily valuable for ruling out the mimics of ABM. In ABM, head
CT/MRI scans are of limited value and are done primarily to rule out parameningeal
suppurative focus or brain abscess, or systemic mimics of meningitis. As mentioned
previously, lumbar puncture takes precedence over neuroimaging if the diagnosis of ABM
is being considered. The EEG is primarily useful in diagnosing encephalitis and is non-
diagnostic in ABM. The main use for EEG is in the early diagnosis of HSV meningoencephalitis
because of the propensity of HSV to localize to the frontal/temporal lobe. In normal hosts,
HHV-6 encephalitis may also localize to the frontal/temporal lobe. EEG abnormalities are
diffuse with most causes of acute viral encephalitis, but is localized very early with HSV-1
meningoencephalitis, which is an important diagnostic clue to its presence (1–5,26,27,41).


EMPIRIC THERAPY OF MENINGITIS
Empiric therapy of ABM depends upon demonstrating or predicting the CNS pathogens so that
an appropriate antibiotic may be selected. If the pathogen can be demonstrated by Gram stain or
inferred from aspects of the history, epidemiological data, systemic laboratory tests, or physical
findings then an antibiotic with an appropriate spectrum can be selected to begin treatment. Early
treatment with an appropriate antibiotic is crucial to the outcome in patients with ABM (1,42–50).
Not only must the antimicrobial being selected to treat ABM be effective against the
pathogen, but it must reach bactericidal concentrations in the CSF with the usual “meningeal
doses.” Certain antibiotics achieve a therapeutic CSF concentration when being in the usual
dose, e.g., chloramphenicol, TMP–SMX, doxycycline, minocycline, and anti-tuberculous drugs,
whereas others require higher than usual doses to penetrate the CSF, e.g., cefepime, meropenem,
and anti-viral drugs. Most other antimicrobials do not achieve sufficient CSF concentration with
usual or even with high dosing, e.g., first/second-generation cephalosporins, vancomycin,
amphotericin (1–3,42–45).
After selecting a drug with the appropriate spectrum for the presumed neuropathogen and
delivering the drug intravenously in a dose that will rapidly achieve bactericidal concentrations
in the CSF, patients are ordinarily treated for a total of two weeks. The main determinants of
antibiotic penetration of the CSF are antibiotic size and the lipid solubility characteristics of the
antibiotic. In general, highly lipid soluble antibiotics penetrate the CSF in the presence or absence
of inflammation. b-Lactam antibiotics do not penetrate the CSF well in the absence of
inflammation. Third- and fourth-generation cephalosporins given in “meningeal doses” do not
penetrate the CNS well, but penetrate sufficiently with sufficiently high degree of activity that
they are effective against common neuro-pathogens exceptL. monocytoenges(1,42–48).
Listeriameningitis is ordinarily treated with “meningeal doses” of ampicillin, i.e., 2 g (IV)
q4h, in penicillin tolerant patients. In patients withListeriameningitis intolerant of penicillin,
chloramphenicol or TMP–SMX may be used. For the treatment of staphylococcal meningitis
due to methicillin-sensitive strains, “meningeal doses” of an anti-staphylococcal penicillin, e.g.,
nafcillin, may be given as a 2 g (IV) q4h dose.
Drugs used to treat methicillin-resistant S. aureus (MRSA) causing ABM include
minocycline and linezolid. Vancomycin does not penetrate the CSF well. Vancomycin CSF
concentrations are*15% of simultaneous serum concentrations. Therefore at the usually used
dose of 1 g (IV) q12h (15 mg/kg/day), CSF concentrations may be inadequate. If vancomycin is
selected to treat MRSA CNS infections, then either 30 to 60 mg/day of vancomycin is
necessary, or the usual dose of vancomycin [15 mg/kg/day (IV)] may be supplemented 20 mg
of intrathecal (IT) vancomycin daily. Linezolid and minocycline penetrate the CSF well and
achieve therapeutic concentrations (42).
The treatment of shunt-related ventriculo-atrial/ventriculo-peritoneal (VA/VP) infec-
tions usually requires shunt removal and the administration of an antibiotic that has a high
degree of activity againstStaphylococcus epidermidisorS. aureus(depending upon the pathogen
isolated that penetrates the CSF in therapeutic concentrations). In patients with meningitis
secondary to open CNS trauma, the antibiotics selected should have a high degree of aerobic
gram-negative bacillary coverage as well as sufficient anti-staphylococcal activity (1,42,51,52).
The preferred drugs for each pathogen-causing meningitis are presented in tabular form
here (Table 12) (1,42).


148 Cunha and Smith

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