of these devices, however, is a common cause of shunt malfunction, as seen in T.A.
The reported incidence of CSF shunt infections in children is approximately 11% in
recent studies and varies in adults from 2.5% to 15% depending on patient factors,
surgical technique, and the type and duration of the procedure performed (i.e., shunt
revision vs. placement of a new device).
95–97 T.A., who has been hydrocephalic since
birth and has a history of multiple shunt procedures, is at high risk for such an
Clinical symptoms associated with infected CSF shunts vary widely from
asymptomatic colonization to fulminant ventriculitis with meningitis. Fever is
common and, in many instances, is the only presenting symptom. CSF findings also
are slightly different in shunt infection compared with acute meningitis: The WBC
count usually is not as elevated, the decrease in CSF glucose is less pronounced, and
the protein value may be normal or slightly elevated. CSF culture is positive in most
98 T.A.’s clinical presentation, CSF findings, and radiographic evidence of
hydrocephalus are highly suggestive of a VP shunt infection. She is febrile and has
altered mental status. The presence of a stiff neck strongly suggests meningeal
involvement. Evaluation of T.A.’s ventricular fluid reveals a slightly elevated WBC
count, with a predominance of PMNs, an elevated protein concentration, and a
slightly lower-than-normal glucose concentration.
and Staphylococcus aureus accounts for roughly one-fourth of all cases. Other less
common pathogens include diphtheroids, enterococci, and Propionibacterium acnes.
Enteric gram-negative bacilli are responsible for a small percentage of cases; these
cases usually occur when the distal end of the shunt is inserted improperly into the
99 The gram-positive cocci in clusters on Gram stain of T.A.’s
CSF strongly suggest a staphylococcal shunt infection. Determining the coagulase
TREATMENT OF CEREBROSPINAL FLUID SHUNT INFECTIONS
CASE 65-4, QUESTION 2: Culture and sensitivity tests of T.A.’s ventricular fluid are positive for S.
should T.A.’s CSF shunt infection be treated?
For T.A.’s CSF shunt infection to be optimally treated, a combined medical and
surgical approach is required. Studies have demonstrated poorer outcomes for
systemic antibiotic therapy alone versus systemic antibiotic therapy plus shunt
100 Because many patients cannot tolerate the complete removal of their shunt
for long, externalization of the distal end of the shunt, or shunt removal and placement
of an external drainage device, often is necessary during systemic antibiotic therapy.
The presence of an externalized device permits sequential sampling of ventricular
fluid and also provides a convenient way to administer antibiotic intraventricularly
(see the following discussion entitled Intraventricular Dosing of Vancomycin).
Although S. epidermidis is not as virulent a pathogen as S. aureus, it is extremely
difficult to eradicate this organism from prosthetic devices such as CSF shunts. This
is because many strains of S. epidermidis produce a mucous film or slime layer
known as glycocalyx, which allows the staphylococci to adhere tightly to the shunt
material, protecting them against phagocytosis.
101 As expected, antibiotic failures are
much more likely with slime-producing strains of S. epidermidis.
Vancomycin is the drug of choice for treatment of shunt infections caused by S.
epidermidis and should be instituted immediately in T.A.
percentage (>60%) of coagulase-negative staphylococci are resistant to methicillin
(e.g., methicillin-resistant S. epidermidis [MRSE]). T.A.’s isolate also is sensitive to
TMP-SMX, as is the case with many strains of MRSE (and also methicillin-resistant
S. aureus [MRSA]), but it must be avoided because T.A. is allergic to this drug
combination. Although not considered a first-line therapy, linezolid has been shown
to be effective for VP shunt infections in small case series and may be considered in
104 Additionally, many staphylococcal isolates (both
S. epidermidis and S. aureus) are susceptible to rifampin, but monotherapy with this
drug is not recommended because of rapid emergence of resistance. However,
rifampin may be used in addition to an antistaphylococcal agent to enhance
bactericidal activity, especially if the prosthesis is retained.
CASE 65-4, QUESTION 3: What would be an appropriate IV dosage for vancomycin in T.A.? What
Vancomycin therapy for T.A.’s CSF shunt infection requires the use of doses
similar to those used for bacterial meningitis. For adults such as T.A., vancomycin
dosages of 30 to 45 mg/kg/day have been endorsed.
11 For children with meningitis or
infected shunts, the recommended dosage of vancomycin is 40 to 60 mg/kg/day, given
IV in two to four divided doses (Table 65-6).
concentrations of vancomycin should be between 15 and 20 mcg/mL.
T.A., who weighs 60 kg, should be started on a vancomycin regimen of 1 g IV
every 8 to 12 hours because her renal function is normal. In either case, trough serum
concentrations should be obtained at steady state to assess whether the initial dosing
regimen is adequate. Another consideration for T.A. is the addition of rifampin to her
vancomycin regimen. This is based on the excellent staphylococcal activity of
rifampin, its moderate CSF penetration, and the potential for synergy between these
106 Whether rifampin plus vancomycin is superior to vancomycin alone
has not been determined. For T.A., it is best to avoid rifampin because evidence
supporting its efficacy is weak, and she currently is taking phenytoin and oral
contraceptives. Rifampin is a potent inducer of hepatic microsomal enzymes, which
can lower serum phenytoin concentrations (possibly resulting in seizure activity) and
increase the possibility of an unplanned pregnancy (from reduced effectiveness of the
Intraventricular Dosing of Vancomycin
CASE 65-4, QUESTION 4: Should T.A. receive intraventricular vancomycin? If so, what would be an
T.A. should receive IV vancomycin. In addition, T.A. has a long history of
hydrocephalus and will require placement of an external drainage device after
removal of her VP shunt. The external drainage device allows for intraventricular
administration of vancomycin, and such treatment should be instituted promptly.
Although dosage recommendations vary from 5 to 20 mg/day, most use 20 mg/day
and this dose should be used for T.A. Also, serial (daily) cultures of CSF are
recommended to monitor her response to therapy. Therapy should be continued for at
least 10 days after sterilization of her ventricular fluid is documented, at which time
In contrast to T.A.’s situation, vancomycin therapy for patients with MRSA
meningitis not associated with a CSF shunt or indwelling ventricular catheter is more
problematic. The latest MRSA clinical practice guidelines from 2011 endorse a 2-
week course of IV vancomycin 15 to 20 mg/kg/dose IV every 8 to 12 hours, with the
potential addition of rifampin 600 mg daily, or 300 to 450 mg every 12 hours.
Additionally, in seriously ill patients, including those with meningitis, a loading dose
of 25 to 30 mg/kg of actual body weight may be considered. Trough concentrations
between 15 and 20 mcg/mL are recommended.
In the setting of drug allergy,
intolerance, or adverse events, alternatives include linezolid 600 mg PO or IV every
12 hours, or TMP-SMX 5 mg/kg/dose IV every 8 to 12 hours.
Although not nearly as common as meningitis, abscesses of the brain parenchyma
(brain abscess) remain an important type of CNS infection. The reported incidence of
brain abscess caused by any type of organism ranges from 0.4 to 0.9 cases per
109 On a busy neurosurgical service, 4 to 10 cases a year
111 For reasons that are not entirely clear, men are more likely to
develop abscesses within the brain than women.
110 Brain abscess can occur at any
age, but the mean age most recently reported is 34 years of age, with a minority of
Despite advances in antimicrobial therapy over the past several decades, mortality
rates from brain abscess have remained above 40% until recently. Developments in
imaging techniques (e.g., CT and MRI scanning), which allow early recognition of
abscesses and the ability to serially monitor the radiographic response to
antimicrobial therapy, have had the most profound impact on reducing morbidity and
mortality from brain abscess. A recent meta-analysis of 123 studies found case
fatality rates declined from 40% to 10% over the decades from 1970 to 2013
whereas the rates of full recovery increased from 33% to 70%. With the combined
medical and surgical approach currently recommended, mortality rates continue to
Brain abscesses most commonly arise from a contiguous suppurative source of
infection (e.g., sinusitis, otitis, mastoiditis, or dental infections).
single abscess cavity usually is found when infection develops from a contiguous
source. In addition, the abscess nearly always is formed in close proximity to the
primary focus of infection (Table 65-9). For example, abscesses of sinusitic origin
more commonly involve the frontal lobe, whereas otitic infections often lead to
temporal lobe abscess formation.
113 Brain abscess also occurs as a consequence of
hematogenous spread of organisms from a primary site of infection (e.g., lung
abscess, endocarditis, osteomyelitis, pelvic, and intra-abdominal infections).
Multiple abscesses suggest a metastatic source of infection. As with meningitis, brain
abscess occurs as an infrequent complication of head trauma or neurosurgery.
identifiable source (cryptogenic abscess) is detected in as many as 30% of cases.
Once an intracranial focus of infection is established, the evolution of brain abscess
involves two distinct stages: cerebritis and capsule formation. The cerebritis stage
evolves gradually over the first 9 to 10 days of infection and is characterized by an
area of marked inflammatory infiltrate that contains a necrotic center surrounded by
an area of cerebral edema. Capsule formation occurs about 10 to 14 days after the
initiation of infection, and once formed, the capsule continues to thicken over a
period of weeks. The stage of abscess development has important implications for
therapy. Although it is best to wait until the capsule is fully formed before attempting
any type of surgical intervention, antimicrobial therapy alone may resolve the
infection if discovered in the early cerebritis stage.
The microbiology of brain abscess is distinctly different from that of meningitis.
Streptococci are implicated in 50% to 70% of cases and include anaerobic as well
as microaerophilic streptococci of the S. milleri group.
particularly Bacteroides species (including B. fragilis) and Prevotella species, are
the second most common cause of brain abscess and are usually in mixed
112 These organisms are followed by staphylococci and gram-negative
bacteria as other common pathogens.
112 Although somewhat imprecise, a reasonable
correlation exists between the various predisposing conditions and the microbiologic
etiology of brain abscess (Table 65-9).
Predisposing Conditions, Microbiology, and Recommended Therapy for
Streptococci (anaerobic and aerobic),
Bacteroides fragilis, gram-negative
Sinusitis Frontal lobe Streptococci (predominantly),
Bacteroides species, gram-negative
bacilli, Staphylococcus aureus,
Dental infection Frontal lobe Fusobacterium species, Bacteroides
Gram-negative bacilli, staphylococci,
In the immunocompromised patient, a diverse group of microorganisms can induce
abscesses within the brain. In patients with AIDS, Toxoplasma gondii is the most
common infectious cause of focal brain lesions.
115 Transplant recipients and those
receiving immunosuppressive therapy are susceptible to infection from Nocardia
species and fungi (e.g., aspergillus or candida species).
Central American countries, cysticercosis remains a common cause of intracerebral
Clinical and Radiologic Features
palpation of his frontalsinuses, and a purulent discharge is noted.
Laboratory evaluation shows the following:
WBC count, 8,000 cells/μL, with 70% PMN, 25% lymphocytes, and 5% monocytes
Erythrocyte sedimentation rate (ESR), 40 mm/hour
Hgb, Hct, platelets, and serum chemistries are within normal limits.
L.Y. has presented to the ED with many signs and symptoms suggestive of
bacterial brain abscess. He is 40 years of age and a man, both of which place him in
a group with the highest likelihood of having a brain abscess. In contrast to the
diffuse nature of meningitis, brain abscess presents as a focal neurologic process.
Notable in L.Y.’s presentation is left-sided (arm and leg) weakness. Symptoms of
brain abscess range in severity from indolent to fulminant, and in most patients, the
duration of symptoms at the time of presentation is ≤2 weeks.
common symptom of brain abscess, occurring in approximately 70% of cases. L.Y.’s
clinical manifestations have become gradually worse over the past week, and his
worsening headaches, increasing drowsiness, and difficulty in concentrating all are
consistent with bacterial brain abscess.
L.Y. presents with the classic triad of fever, headache, and focal neurologic
deficits. Although this triad should always be looked for, fewer than half of patients
with confirmed bacterial brain abscess present in this manner.
The absence of fever does not rule out infection because fever is found in <50% of
113 Focal neurologic deficits are present in approximately 50% of patients
and vary in nature and severity in relation to the location and size of the abscess and
surrounding cerebral edema. Although L.Y. does not have a history of seizure
activity, approximately 25% of patients experience partial seizures that often become
generalized. Papilledema and nuchal rigidity occur in ≤25% of cases and often are
not useful in confirming the diagnosis. Symptoms associated with a contiguous focus
of infection should always be sought, and in some situations, they may dominate the
112 L.Y. has a history of sinus infection, and the pain on palpation of
his sinuses coupled with the purulent sinus drainage suggests active infection at this
As can be seen from L.Y.’s test results, laboratory evaluation usually is not very
helpful when diagnosing brain abscess. L.Y. does not have a peripheral leukocytosis,
but he does have an elevated ESR. A normal peripheral WBC count is not unusual in
patients with intracranial suppuration. The ESR often is elevated
in brain abscess, but this test is nonspecific and only indirectly supports the
L.Y. did not have a lumbar puncture because this procedure is contraindicated for
diagnosing brain abscess. The diagnostic yield from CSF is low because chemistries
(e.g., protein, glucose, WBC) usually are normal and culture of the CSF in patients
with brain abscess is unlikely to yield the causative pathogen. More important,
performing a lumbar puncture in patients with space-occupying lesions of the brain
can produce cerebral herniation as a consequence of the shifting pressure gradient
induced within the cranial vault after insertion of the lumbar puncture needle.
Of paramount importance is the abnormality detected on the CT scan of L.Y.’s
brain. When dye is injected before the CT scan, brain abscesses will appear to “ring
enhance.” Furthermore, cerebral edema can be identified as a variable hypodense
region immediately surrounding the abscess cavity. As stated earlier, CT and MRI
scanning techniques have revolutionized the diagnosis and treatment of brain
In general, a good correlation exists between the clinical and
radiologic response to therapy of bacterial brain abscess.
CASE 65-5, QUESTION 2: How should L.Y.’s brain abscess be treated?
A combined medical and surgical approach is the best form of therapy for L.Y.’s
brain abscess. Response rates to antimicrobial therapy alone have been
disappointing, and with a few exceptions, surgical intervention is necessary to ensure
optimal results. Modern stereotactic neurosurgical techniques allow almost any brain
abscess that is ≥1 cm in diameter to be drained via stereotactic aspiration, regardless
of location. Primary medical therapy may be indicated if imaging does not show a
central cavity in the abscess or if surgery is withheld for other reasons such as poor
The two types of surgical approaches for brain abscess are (a) stereotactic
navigation with needle aspiration and (b) intraoperative ultrasonography through a
burr hole or craniotomy for direct abscess drainage.
113 Stereotactic aspiration of
abscess is highly effective and is associated with lower morbidity and mortality than
120 Modern medical advances leave total resection with a very limited
role unless an abscess is superficial or when there is high suspicion of fungal or
ANTIMICROBIAL PENETRATION INTO BRAIN ABSCESS
Antimicrobial therapy is an essential component of brain abscess therapy.
Penetration of antibiotics into brain abscess fluid has not been studied as carefully as
penetration into CSF, and as discussed earlier, the barrier involved is different ( Fig.
7 Penicillins and cephalosporins penetrate adequately into abscess fluid, but
certain agents (e.g., penicillin G) may be susceptible to degradation by enzymes
present within the abscess milieu.
110 Third-generation cephalosporins (e.g.,
cefotaxime, ceftriaxone) penetrate sufficiently into the abscess and thus are
appropriate choices when gram-negative bacteria are present.
achieves abscess fluid concentrations equal to or in excess of serum levels and is
bactericidal against strict anaerobes. The unique mechanism of action of
metronidazole makes it particularly useful in the necrotic core of the cavity, where
the oxidation-reduction potential is low and bacteria replicate slowly or are dormant.
For these reasons, metronidazole is the drug of choice for anaerobic gram-negative
110 Vancomycin and carbapenems also penetrate sufficiently
122 Although specific abscess-penetration data are
unavailable, successful treatment of cerebral nocardiosis with TMP-SMX and CNS
toxoplasmosis with clindamycin suggests that these compounds also achieve
adequate penetration into cerebral abscess cavities.
When antibiotic therapy should be instituted depends on the status of the patient and
the stage of abscess development. For patients diagnosed during the cerebritis stage,
before formation of a well-circumscribed capsule, surgery should be delayed and
antimicrobial therapy begun in patients with significant symptoms.
formation already has taken place and if the patient’s clinical status allows, it is
reasonable to delay initiation of antibiotics until after surgery if surgery is to be
performed within hours to increase the microbiologic yield from tissue and fluid
samples. If the disease is fulminant, antibiotics must be instituted promptly and
surgical intervention performed as quickly as possible.
L.Y.’s clinical presentation suggests an advanced brain abscess. The presence of
ring enhancement on CT and the onset of symptoms over 2 weeks support this
conclusion. Because he is not critically ill, antibiotic therapy may be delayed until
surgery is performed. Specimens obtained from the surgical procedure should be sent
for aerobic and anaerobic culture and an immediate Gram stain.
Initial antibiotic therapy for brain abscess needs to be sufficiently broad to cover
the most likely pathogens (Table 65-9). When the implicated source is contiguous
such as oral, otogenic, or sinus, metronidazole plus ceftriaxone (with the addition of
vancomycin with a sinus source) is recommended.
113 Metronidazole will provide
coverage for strict anaerobes, including Bacteroides and Prevotella species. When
the implicated source is head trauma with skull fracture or is associated with a
neurosurgical procedure, empiric therapy should consist of vancomycin,
metronidazole, and a third- or fourth-generation cephalosporin. For hematogenous
sources, a third-generation cephalosporin, metronidazole, and vancomycin are
113 Vancomycin is added to cover staphylococcal infection.
For L.Y., therapy with ceftriaxone 2 grams IV Q 12 hours, vancomycin 1 gram IV
Q 8 hours, and metronidazole 500 mg IV Q 8 hours should be started postoperatively
ADJUNCTIVE CORTICOSTEROID THERAPY
Adjunctive corticosteroid therapy for bacterial brain abscess is controversial.
Steroids can interfere with antibiotic penetration into abscesses and obscure the
interpretation of serial CT scans when assessing response to therapy. Therefore,
steroids are indicated only if significant cerebral edema is present, particularly if it
is accompanied by rapid neurologic deterioration.
dexamethasone because his mental status is only mildly depressed and the cerebral
edema seen on CT scan is not massive.
ADJUNCTIVE ANTICONVULSANT THERAPY
L.Y. has shown no sign of seizure activity thus far and, therefore, does not require
anticonvulsant therapy. Anticonvulsants should be used in the acute setting when
seizures are present, however.
121 Agents with activity against partial and complex
partial seizures are preferred (e.g., phenytoin, carbamazepine, and potentially
levetiracetam). The long-term use of anticonvulsants depends on whether seizure
activity persists. Insufficient information exists regarding how long to continue
anticonvulsants in such cases. Therefore, discontinuation of these agents must be
No formal guidelines are available regarding the optimal duration of therapy for
bacterial brain abscess. Given the serious nature of the infection and the difficulty
associated with antibiotic penetration, therapy with high-dose IV therapy should
continue for at least 6 to 8 weeks.
113 The duration of therapy should be
evaluated on a case-by-case basis. In an attempt to ensure complete eradication of
infection, some experts recommend long-term (2–6 months) oral antibiotics after the
IV course, provided agents with good oral absorption and activity against the
offending pathogens are available.
CASE 65-5, QUESTION 3: How should L.Y. be monitored for therapeutic response and toxicity?
Although L.Y. is on antibiotic therapy, weekly or biweekly CT scans should be
obtained to evaluate abscess resolution. His clinical response to therapy also should
be assessed daily. If therapy is effective, L.Y.’s mental status should improve
gradually (e.g., he will become more alert and oriented) over a period of several
days. L.Y.’s headaches and hemiparesis (weakness in his arm and leg) also should
resolve eventually. It may take a week or longer, however, to see a complete
In general, radiologic improvement (i.e., reduction in
abscess size) correlates reasonably well with clinical response, but not always.
Persistent symptoms or failure to detect a reduction in abscess size on CT scan or the
appearance of new abscesses may indicate improper antimicrobial therapy or the
121 Repeated surgical intervention with appropriate
reculturing may be required in some instances to optimize therapy.
Adverse effects associated with the penicillin G therapy that L.Y. is receiving are
similar to those of other β-lactam antibiotics. Seizures are a potential complication
when high doses of penicillin are used in the presence of a mass lesion in the
125 L.Y. should be observed closely by those providing care and questioned
regularly for any evidence of seizure activity. Metronidazole usually is well
tolerated, but may also cause neurotoxicity, most commonly peripheral neuropathy.
L.Y. should be assessed for the presence of numbness or tingling in his hands or feet.
Seizures, although uncommon, occasionally occur with metronidazole. If L.Y.
experiences peripheral neuropathy or seizures, a switch to meropenem would be
appropriate. Other adverse effects associated with metronidazole include mild
nausea, brownish discoloration of the urine, and the potential for a disulfiram-like
reaction with concomitant ethanol ingestion.
126 L.Y. should be counseled regarding
the possibility of gastric upset and discoloration of the urine, and he should be
strongly cautioned to avoid alcoholic beverages while receiving metronidazole.
Given his young age, the absence of significant underlying diseases, and the relative
early detection of his brain abscess, there is every reason to expect a good response
to his treatment and, eventually, a complete resolution of his abscess.
A full list of references for this chapter can be found at
http://thepoint.lww.com/AT11e. Below are the key references and website for this
chapter, with the corresponding reference number in this chapter found in parentheses
Brouwer MC et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev.
Brouwer MC et al. Brain Abscess. N EnglJ Med. 2014;371:447–456. (113)
observationalstudy. Lancet Infect Dis. 2014;14:813–819. (70)
de Gans J et al. Dexamethasone in adults with bacterial meningitis. N EnglJ Med. 2002;347:1549. (41)
Central Nervous System Infections. Clin Microbiol Rev. 2010;23:858. (29)
correction appears in N EnglJ Med. 2005;352:950]. N EnglJ Med. 2004;351:1849. (72)
COMPLETE REFERENCES CHAPTER 65 CENTRAL
Thigpen MC et al. Bacterial meningitis in the United States, 1998–2007. N EnglJ Med. 2011;364:2016.
Elsevier/Saunders; 2012;37:202–213.
Clinical Neuroscience. Philadelphia, PA: Elsevier/Sauders; 2010;5:83–91.
Cook AM et al. Intracerebroventricular administration of drugs. Pharmacotherapy. 2009;29:832–845.
Pediatr Infect Dis J. 1992;11:423.
Van de Beek D et al. Community-acquired bacterial meningitis in adults. N EnglJ Med. 2006;354:44–53.
Bacterial Meningitis Study Group. J Infect Dis. 1990;162:1316.
b invasive disease among infants and children—United States, 1998–2000. MMWR Morb Mortal Wkly Rep.
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