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CHAPTER 71: Bacterial Infections of the Central Nervous System 651

Amphotericin B: Amphotericin B deoxycholate is used infrequently in surgical patients: systematic review and meta-analysis of randomized
the ICU setting because of its renal toxicity and infusion-related side clinical trials. J Antimicrobial Chemother. 2006;57:628-638.
effects, which can be especially problematic in severely ill patients
in an ICU. However, there are instances in which it may be neces- • Puig-Asensio M, Pemán J, Zaragoza R, Garnacho-Montero J,
107
sary to use amphotericin B, which is fungicidal for most Candida Martín-Mazuelos E, Cuenca-Estrella M, et.al. Impact of therapeu-
species. For example, amphotericin B is useful for treating urinary tic strategies on the prognosis of candidemia in the ICU. Crit Care
108
tract infections due to C krusei and C glabrata that are resistant to Med. 2014; EPub PMID 24557426.
fluconazole, and in many neonatal ICUs, amphotericin B is the • Smith JA, Kauffman CA. Recognition and prevention of nosoco-
97
preferred agent to treat invasive candidiasis. In both of these cases, mial invasive fungal infections in the intensive care unit. Crit Care
109
amphotericin B deoxycholate is the formulation used. The dose of Med. 2010;38(suppl):S380-S387.
amphotericin B deoxycholate is usually 0.7 to 1.0 mg/kg daily, but for
Candida urinary tract infections, 0.3 to 0.6 mg/kg daily is adequate.
Infusion time is 4 to 6 hours for amphotericin B deoxycholate. REFERENCES
In most adult ICUs, lipid formulations of amphotericin B are pre- Complete references available online at www.mhprofessional.com/hall
ferred in an attempt to decrease toxicity. There are three preparations
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available: liposomal amphotericin B (L-AmB), amphotericin B lipid
complex (ABLC), and amphotericin B colloidal dispersion (ABCD)
(Table 70-8). The latter is used infrequently because infusion-related CHAPTER Bacterial Infections of the
side effects occur as frequently with this formulation as with amphoteri-
kinetic attributes. The usual dose for treating invasive candidiasis or 71
cin B deoxycholate. Each of these preparations has different pharmaco- Central Nervous System
110
candidemia is 3 mg/kg for L-AmB and 5 mg/kg for ABLC given once Allan R. Tunkel
daily over a 2-hour period. 100 W. Michael Scheld
Although the lipid formulations are less toxic, they still cause some
degree of renal insufficiency, as well as hypokalemia and hypomagnese- KEY POINTS
mia. Giving a bolus of 500 mL of normal saline prior to the infusion of
any amphotericin B formulation is recommended to try to obviate the • Adults with bacterial meningitis usually present clinically with
risk for nephrotoxicity. Other nephrotoxic agents, such as aminogly- fever, headache, meningismus, and/or signs of cerebral dysfunc-
111
cosides, should be avoided when using amphotericin B. tion; elderly patients, however, may present with insidious disease
manifested only by lethargy or obtundation, variable signs of men-
ingeal irritation, and no fever.
KEY REFERENCES • Occasionally, a patient with acute bacterial meningitis has a low
cerebrospinal fluid (CSF) white cell count despite high bacterial
• Bergman SJ, Tyagi I, Ronald K. Antifungal dosing in critically ill concentrations in CSF; therefore, a Gram stain and culture should be
patients. Curr Fungal Infect Rep. 2010;4:78-86. performed on every CSF specimen, even if the cell count is normal.
• Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species • Neuroimaging techniques have little role in the diagnosis of acute
infections in critically ill non-immunosuppressed patients. Lancet bacterial meningitis. However, computed tomography (CT) should
Infect Dis. 2003;3:685-702. be performed before lumbar puncture when a space-occupying
• Eggimann P, Garbino J, Pittet D. Management of Candida species lesion of the central nervous system (CNS) is suspected. Clinical
infections in critically ill patients. Lancet Infect Dis. 2003;3:772-785. features for which patients should undergo CT scanning prior
• Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole to lumbar puncture are immunocompromise, a history of CNS
disease, a history of seizure within 1 week before presentation,
therapy impacts mortality in patients with candidemia: a multi- papilledema, and specific neurologic abnormalities.
institutional study. Clin Infect Dis. 2006;43:25-31.
• Hollenbach E. Invasive candidiasis in the ICU: evidence based and • Empirical antimicrobial therapy, based on the patient’s age and
underlying disease status, should be initiated as soon as possible in
on the edge of evidence. Mycoses. 2008;51:25-45. patients with presumed bacterial meningitis; therapy should never
• Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, man- be delayed while diagnostic tests such as CT are awaited.
agement, and risk factors for death of invasive Candida infections • Adjunctive dexamethasone therapy has been shown to decrease the
in critical care: a multicenter, prospective, observational study in morbidity rate in infants and children with acute Haemophilus influen-
France (2005-2006). Crit Care Med. 2009;37:1612-1618. zae type b meningitis and, if commenced with or before antimicrobial
• Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment therapy, may also be beneficial for pneumococcal meningitis in child-
of Candida bloodstream infection until positive blood culture hood. Adjunctive dexamethasone is also associated with decreased
results are obtained: a potential risk factor for hospital mortality. morbidity and mortality rates in adults with pneumococcal meningitis
Antimicrob Agents Chemother. 2005;49:3640-3645. when administered before the first dose of antimicrobial therapy.
• Pappas PG, Kauffman CA, Andes D, et al. Clinical practice • Fewer than 50% of patients with brain abscess present with the
guidelines for the management of candidiasis: 2009 update by classic triad of fever, headache, and focal neurologic deficit;
the Infectious Diseases Society of America. Clin Infect Dis. the clinical presentation of brain abscess in immunosuppressed
2009;48:503-535. patients may be masked by the diminished inflammatory response.
• Pappas PG, Rex JH, Lee J, et al. A prospective observational study • The diagnosis of brain abscess has been revolutionized by the develop-
of candidemia: epidemiology, therapy, and influences on mortal- ment of CT; magnetic resonance imaging offers advantages over CT in
ity in hospitalized adult and pediatric patients. Clin Infect Dis. the early detection of cerebritis, cerebral edema, and satellite lesions.
2003;37:634-643. • Aspiration of brain abscess under stereotaxic CT guidance is useful
• Playford EG, Webster AC, Sorrell TC, Craig JC. Antifungal agents for microbiologic diagnosis, drainage, and relief of increased intra-
for preventing fungal infections in non-neutropenic critically ill and cranial pressure.

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