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660 PART 5: Infectious Disorders

by hemorrhage. At the time of aspiration, a specimen should be sent for organism) and the high concentrations it attains in brain abscess pus,
Gram stain (and other special stains, eg, Ziehl-Nielsen, modified acid- even with concomitant corticosteroid administration. In addition, met-
fast, and silver stains, when appropriate), routine culture, and anaerobic ronidazole may improve mortality rates in patients with brain abscess. In
culture. In patients with a likely bacterial brain abscess, 16S rDNA cases in which S aureus is a likely infecting pathogen (eg, cranial trauma
metagenomic analysis and amplification may be important in patients or prior neurosurgery), vancomycin (which penetrates into brain abscess
with histologic evidence of brain abscess and negative cultures; two fluid) should be used empirically while awaiting results of in vitro sus-
studies found that this technique dramatically increased the number of ceptibility testing. The penetration of clindamycin, erythromycin, and the
agents identified, 56,57 although confirmation is needed to determine the first-generation cephalosporins into brain abscesses is usually inadequate
importance of these multiple agents as true pathogens in patients with to achieve therapeutic concentrations, thus precluding their use in this
brain abscess. The use of this modality in the treatment of brain abscess setting. For empirical therapy when members of the Enterobacteriaceae
is discussed under Surgical Therapy in the section Treatment. are suspected (eg, in cases of abscess of otitic origin), a third-generation
Lumbar puncture is contraindicated in patients with suspected or cephalosporin or trimethoprim-sulfamethoxazole should be used.
proven brain abscess because of the risk of life-threatening cerebral One regimen that has theoretical advantages and covers a broad range
herniation after removal of CSF. When lumbar puncture is performed, of possible infecting bacterial pathogens is metronidazole, vancomycin,
the CSF profile is nonspecific, with a predominantly mononuclear and a third-generation cephalosporin (cefotaxime or ceftriaxone; see
pleocytosis and an elevated protein concentration. Hypoglycorrhachia Table 71-7). In addition to activity against gram-negative bacilli, these
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is present in only 25% of cases, and fewer than 10% of CSF cultures are third-generation cephalosporins have excellent antistreptococcal activ-
positive. Microorganisms usually are not demonstrated on Gram stain, ity and possess antistaphylococcal action. However, it is important to
unless the abscess has ruptured into the subarachnoid space or there is note that there are no clinical trials comparing this regimen with tradi-
accompanying meningitis. tional penicillin-containing formulas. If P aeruginosa is a likely infecting
■ TREATMENT pathogen, ceftazidime, cefepime, or meropenem is the agent of choice.
However, if ceftazidime is the third-generation cephalosporin used in
Antimicrobial Therapy: Perhaps related to the alteration of the blood- empirical therapy of brain abscess, the regimen must also include peni-
brain barrier in the area of the brain abscess, there is increased pen- cillin G to treat a possible streptococcal infection because ceftazidime
etration of normally excluded antibiotics into the brain. However, this has unreliable activity against gram-positive organisms.
increased penetration into the brain does not predict penetration into Once an infecting pathogen is isolated, antimicrobial therapy can be
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cerebral abscesses. Brain abscess concentrations of antibiotics have modified (Table 71-8). Antimicrobial therapy with large-dose intra-
been measured, and several generalizations can be made: (a) met- venous antibiotics should be continued for 6 to 8 weeks and is often
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ronidazole can be expected to achieve inhibitory levels for sensitive followed by oral antibiotic therapy for 2 to 3 months, if an appropriate
anaerobic microorganisms and (b) concentrations of various penicil- agent is available, although the efficacy and necessity of this approach
lins and cephalosporins in brain tissue and abscess are usually poor, has not been established. A shorter course (3-4 weeks) may be adequate
although when given in large parenteral doses, these agents achieve for patients undergoing excision of the abscess. Surgical therapy (see
therapeutic concentrations for sensitive microorganisms. below) is often required for treatment of brain abscess, although certain
When a diagnosis of brain abscess is made, whether presumptively on subgroups of patients can be managed without surgery. These include
the basis of radiologic studies or through aspiration of the abscess, anti- patients with medical conditions that increase the risks from surgery,
microbial therapy should be initiated. Aspiration may provide an etiologic patients with multiple abscesses or an abscess in a deep or dominant
diagnosis on Gram stain examination, but when aspiration is impractical location, patients with coexisting meningitis or ependymitis, patients in
or delayed, we recommend empirical therapy based on the likely etio- whom antimicrobial therapy results in early abscess reduction and clini-
logic agent, if a predisposing condition can be identified (Table 71-7). cal improvement, and patients with an abscess smaller than approxi-
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Because of the high rate of isolation of streptococci (particularly the mately 3 cm. Patients treated with medical therapy alone may require
S milleri group) from brain abscesses of various etiologies (see Table 71-6), more prolonged treatment (up to 12 weeks), with careful clinical and
high-dose penicillin G (20-24 million U/day) or another drug that is radiographic follow-up. In all patients, biweekly neuroimaging up to
active against this organism (eg, a third-generation cephalosporin, either
cefotaxime or ceftriaxone) should be included in the initial therapeutic
regimen. Penicillin is also active against most anaerobic species, with TABLE 71-8 Antimicrobial Therapy for Brain Abscess
the notable exception of B fragilis, which is isolated in a high percentage Organism Standard Therapy Alternative Therapies
(20%-40%) of brain abscess cases. When B fragilis is suspected, we rec- a
ommend the addition of metronidazole (7.5 mg/kg every 6 hours). The Streptococcus milleri and Penicillin G Third-generation cephalosporin,
advantages of metronidazole over other agents include its bactericidal other streptococci vancomycin
activity against B fragilis (the others are frequently bacteriostatic for this Bacteroides fragilis Metronidazole Clindamycin
Fusobacterium sp, Penicillin G Metronidazole
TABLE 71-7 Empirical Antimicrobial Therapy for Brain Abscess Actinomyces
Staphylococcus aureus Nafcillin Vancomycin c
Predisposing Condition Antimicrobial Regimen
Enterobacteriaceae b Third-generation Aztreonam, trimethoprim-
Otitis media or mastoiditis Metronidazole plus a third-generation cephalosporin a
cephalosporin a sulfamethoxazole, fluoroquinolone,
Sinusitis Vancomycin plus metronidazole plus a third- meropenem
generation cephalosporin a
Haemophilus sp Third-generation Aztreonam, trimethoprim-
Dental sepsis Penicillin plus metronidazole cephalosporin a sulfamethoxazole
Cranial trauma or postneurosurgical Vancomycin plus a third-generation cephalosporin a Nocardia asteroides Trimethoprim- Minocycline, third-generation
state sulfamethoxazole cephalosporin, imipenem, meropenem,
a
Congenital heart disease Third-generation cephalosporin a amikacin
Unknown Vancomycin plus metronidazole plus a third- a Cefotaxime or ceftriaxone.
generation cephalosporin a b Choice based on in vitro susceptibility testing.
a Cefotaxime or ceftriaxone; ceftazidime or cefepime is used if Pseudomonas aeruginosa is suspected. c Use vancomycin if methicillin-resistant S aureus is isolated or suspected.

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