US Pharm. 2014;39(4):HS2-HS7.
ABSTRACT: The management of hydrocephalus, the
accumulation of cerebrospinal fluid (CSF) in the ventricles of the
brain, often includes shunt implantation to prevent long-term effects.
Shunts are drainage devices designed to sustain intracranial pressure
and prevent further CSF accumulation, but they can introduce pathogens
into the central nervous system. This can lead to infections and
sequelae, such as seizures, shunt failure, meningitis, sepsis, and
encephalitis. Infections may be prevented by using aseptic techniques,
chemoprophylaxis, and/or antibiotic-eluting shunts. Treatment of a shunt
infection may include removal of the infected hardware, placement of a
drainage device, and use of IV or intraventricular antibiotics.
Hydrocephalus is a condition characterized by accumulation
of cerebrospinal fluid (CSF) in the ventricles or subarachnoid space in
the brain, leading to increased intraventricular pressure and
ventricular dilation. A common etiology of hydrocephalus is impairment
of CSF drainage.1,2 The occurrence of hydrocephalus in the
United States and Europe has been estimated at 0.5 to 0.8 per 1,000
births and is often secondary to spina bifida, intracranial hemorrhage,
or congenital etiology.1,3 Other potential causes of
hydrocephalus include myelodysplasia, tumors, meningitis, posterior
fossa cyst, Dandy-Walker malformation, or aqueductal stenosis.4
Mechanical shunting is the primary treatment for
hydrocephalus. Hydrocephalus-related shunt placements are the most
common neurosurgical procedure performed in children, but they also have
the highest failure rate.5 Over 40,000 shunt placements are performed annually in the U.S., with an estimated inpatient mortality rate of 2.7%.5,6
Introduction of common skin flora and other pathogens, both
perioperatively and postoperatively, can lead to shunt infections and
result in shunt failure.
The rate of shunt infections is estimated at 1.6% to 16.7% in adult patients but up to 20% in pediatric patients.2,7
This increased occurrence in the pediatric population is thought to be
due to lack of immunity (particularly <1 year of age), prematurity
(<35 weeks’ gestational age), exposure to potential pathogens,
concomitant morbidities, and other physiological factors.3,4
Pediatric patients tend to develop shunt infections sooner than adults,
with most infections occurring within the first 30 to 60 days post
Patients who are <5 years of age and adults aged 50 to 59 years appear to have the greatest incidence of shunt infections.1 Risk
factors for shunt infection may include younger age, postoperative CSF
leak, intraventricular hemorrhage, multiple shunts, shunt revision
surgery in the past 90 days, shunts placed immediately post meningitis,
prolonged hospital stay (>1 month), and previous shunt infection.2,4,7,8
Complications related to shunt infections include shunt malfunctions,
short- or long-term cognitive impairment, sepsis, meningitis, and
lengthened hospital stay.1,4,8
The most common types of shunts are summarized in TABLE 1.
This article will focus on the two most utilized shunts:
ventriculoperitoneal (VP) and ventriculoatrial (VA) shunts. VP shunts,
the more common of the two, work by diverting CSF to the peritoneum,
whereas VA shunts shift the CSF to the atrium of the heart.2,9,10
Pathogenesis of Shunt Infections
Shunt contamination is often caused when the proximal end
of the shunt comes in contact with normal skin flora. This can occur
postoperatively due to a wound infection or perioperatively during
surgical implantation.11 Gram-positive bacteria, such as coagulase-negative Staphylococcus epidermidis and Staphylococcus aureus, are responsible for 45% to 60%1-3,12 and 20% to 33%2,3 (with one report up to 80%4)
of shunt infections, respectively. These pathogens are closely
associated with early shunt infections (occurring within 4 weeks of
Late shunt infections can occur several months after shunt
surgery and account for approximately 15% of shunt-related infections.3 In many cases, these late infections can be caused by either gram-positive bacteria, like Streptococcus or Enterococcus species, or gram-negative bacteria, most commonly Pseudomonas aeruginosa, if the patient has experienced a bowel perforation or peritonitis (primarily seen in VP shunts).2 The most common pathogens associated with shunt infections are summarized in TABLE 2.1-4,11 Infections increase the likelihood of shunt-related complications and failures.
Prevention of Shunt Infections
Methods employed to prevent a shunt infection include
using sterile technique, systemic antibiotics, and
antibiotic-impregnated catheters. Aseptic surgical technique has been
shown to help reduce the risk of shunt infections. A standardized
surgical protocol, including preoperative washing of the patient’s hair
with chlorhexidine shampoo, double gloving by all members of the
surgical team, and the use of antibiotic-impregnated shunts (AIS), that
was implemented by four children’s hospitals demonstrated an infection
reduction rate from 8.8% to 5.7%.13
Systemic prophylactic antibiotics may be utilized during
the procedure and in the initial 24 hours after shunt placement.
According to a meta-analysis, the use of systemic, prophylactic
antibiotics and antibiotic-impregnated catheters reduced the rate of
shunt infections.9 This same study compared use of systemic,
prophylactic antibiotics versus placebo for the reduction of shunt
infection and found that the antibiotics decreased the rates of shunt
infections (odds ratio [OR], 0.52).9 While the most
appropriate prophylactic antibiotic for shunt placement was not well
defined in the past, most clinicians use IV cefazolin or vancomycin for
surgical prophylaxis.2,14 Recent guidelines recommend
cefazolin for neurosurgical fluid-shunting procedures, with clindamycin
and vancomycin as alternatives for allergic patients.15
AIS catheters have commonly been used to prevent shunt infections since their introduction in 2002.16 Most devices are impregnated with a combination of rifampicin and clindamycin.4,16,17
They are designed to target the colonization of gram-positive bacteria
that produce a glycoprotein biofilm that adheres to the catheter
surface.16 One meta-analysis looked at the use of
antibiotic-impregnated catheters versus standard catheters and found
that the use of antibiotic-impregnated catheters was associated with
decreased rates of shunt infection (OR, 0.21). It was concluded in this
meta-analysis that the use of both systemic antibiotic prophylaxis and
antibiotic-impregnated catheters could be beneficial in the reduction of
A retrospective trial was also conducted in pediatric
patients who had undergone shunt insertion during a 3-year time frame.
For the first 18 months, patients received nonantibiotic-impregnated
catheters; for the next 18 months, any new patient requiring shunt
placement received antibiotic-impregnated catheters. All children were
followed for 6 months after shunt placement. The children with
nonantibiotic-impregnated catheters had an infection rate of 12%,
whereas infection was seen in only 1.4% of the children with
antibiotic-impregnated catheters.18 A more recent review of
15 trials also concluded that antibiotic-coated catheters reduce the
clinical infection rate, particularly in patients who have long-term
catheters, which was different from some previous analyses.19
Preventing shunt infections through prophylaxis and the use of AIS catheters has been shown to reduce cost of patient care.20
It is estimated that the cost to treat a shunt infection can range from
$17,300 to $48,454 per patient, leading to an estimated annual hospital
cost in the U.S. of $2 billion.16,17 Although each AIS
catheter costs an average of $400, the amount of money saved by
preventing infection and/or reinfection can provide significant
long-term savings.16 These savings are due to a 2.4-fold
decreased likelihood of infection and decreased time in the hospital as a
result of infection. It has been reported that these savings would
amount to over $440,000 per 100 patients shunted.17
Diagnosing Shunt Infections
General shunt infection symptoms include headache, nausea,
vomiting, inflammation of the surgical site, neurologic abnormality,
fever, and seizure.2,3 Patient-specific clinical
manifestations of shunt infections depend on the type of shunt
implanted. VP shunts can be associated with peritonitis, anorexia,
irritability, and abdominal pain,8 while VA shunts can be associated with sepsis and endocarditis.2,3
If clinical manifestations such as altered mental status, erythema
surrounding the shunt site, fluid along the shunt track, purulent
discharge, papilledema, bulging fontanel, nuchal rigidity, or obvious
CSF leakage are seen, the patient should be evaluated with CSF analysis,
blood cultures, and cerebral imaging.8
CSF analysis predictive for infection includes increased
white blood cell count, increased protein concentrations, and decreased
glucose levels; the CSF should also be cultured and gram-stained. Blood
cultures are more useful indicators of VA shunt infections as opposed to
VP shunt infections.11 Cerebral imaging can be used to
identify ventriculitis or evidence of CSF obstruction. Abdominal imaging
may also be used to identify VP shunt malfunction.
Currently, there are no practice guidelines for the
treatment of shunt infections; however, the removal of the infected
hardware, placement of an external ventricular drain, cultures, and
treatment with IV or intraventricular anti-biotics are all shown to be
part of an effective management process.2
Current recommendations for the empirical treatment of
central nervous system (CNS) infection in the presence of a shunt
recommend using IV vancomycin in combination with an agent that has
adequate gram-negative coverage, such as cefepime, ceftazidime,
cefotaxime, or meropenem. The ability of a medication to penetrate the
CSF as well as the activity of the antibiotic against the bacterial
biofilm are also important to consider for antibiotic choice.21 Such agents should be administered until the pathogen is identified and definitive treatment determined.22,23
In a VP shunt, the distal tip of the shunt lies within the peritoneal
cavity and is more susceptible to gram-negative bacteria; gentamicin may
be added for synergy.2 Empirical antimicrobial therapy and dosing recommendations for shunt infections are summarized in TABLE 3.2,18,22,23
For patients refractory to vancomycin therapy, linezolid
10 mg/kg every 8 hours has been shown to be effective as monotherapy in
pediatric patients.21 The addition of rifampin as adjunctive therapy may also be considered due to its penetration into the CNS.24
The length of antibiotic therapy depends largely on the surgical
approach used, the type of shunt, and the pathogen involved, with one
study reporting a duration of therapy range of 4 to 47 days.25,26 More specifically, 7 to 10 days has been suggested for treatment duration,23 with a longer course (10-14 days) recommended for gram-negative infections.2
In the case of complicated or treatment-resistant shunt
infections, clinicians should consider intrathecal or intraventricular
administration of antibiotics for increased efficacy due to their
ability to achieve higher bactericidal concentrations within the CNS.23 Vancomycin and gentamicin are commonly used in this situation; however, there are no definitive recommendations on their use.22,23
Fungal Shunt Infections
A fungal shunt infection is considered to be rare, with one study reporting an incidence rate of 0.01%.27 The most common pathogens responsible for a fungal shunt infection are Candida species (including C albicans, C parapsilosis, and C tropicalis), which cause 75% of fungal cases. Other organisms include Histoplasmosis species, Cryptococcus neoformans, and Aspergillus species. The primary treatment for fungal shunt infections is liposomal amphotericin B 3 to 5 mg/kg/day for at least 12 weeks.27 For patients intolerant of amphotericin B, 5-flucytosine may be an alternative.28
This is often followed by treatment with fluconazole 600 to 800 mg/day
or itraconazole 200 mg two to three times daily for up to 1 year in
immunocompetent patients and potentially life-long therapy in patients
who are immunocompromised.27
Shunt infections are a risk factor associated with
hydrocephalus treatment. Infection prevention has been demonstrated with
empirical antibiotics and the use of AIS catheters, combined with
proper aseptic technique, to significantly decrease the rate of
infection and reduce the risk of comorbid sequelae. There are currently
no guidelines for the treatment of shunt infections; however, IV
empirical therapy involving both gram-positive and gram-negative
coverage, such as vancomycin and a third-generation cephalosporin, would
be recommended. Intraventricular antibiotics may also be needed for
maximal bactericidal CNS concentration.
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