AACN Advanced Critical Care

Volume 24, Number 1, pp.612

2013, AACN

Complex

Rhythms

Earnest Alexander, PharmD, and

Gregory M. Susla, PharmD
Department Editors

Ventriculoperitoneal Shunt Infections in Adult Patients

Diana L. Wells, PharmD, BCPS
John M. Allen, PharmD, BCPS

entriculoperitoneal (VP) shunt infections are a common complication

in patients with these devices. Because children with cerebrospinal fluid
(CSF) shunts are more likely to experience infections, considerably more studies
evaluating this complication in children are available than studies evaluating
this complication in adults.13 The available literature on VP shunt infections in
adults consists mainly of retrospective chart reviews and case reports, making it
difficult to determine the optimal care these patients should receive when they
have an acute infection. As a result of the potential complications of VP shunt
infections, patients often are treated in the intensive care unit and nurses play a
major role in ensuring the optimal care for these patients. This column summarizes the published data describing the incidence and risk factors, microbiology,
diagnosis, treatment, and prevention of VP shunt infections in adult patients.
VP Shunts
Cerebral shunts are primarily used to manage hydrocephalus, a condition in
which a buildup of excess CSF accumulates in the ventricles of the brain. The
use of cerebral shunts to manage hydrocephalus dates back to the mid-20th
century.4 Left untreated, hydrocephalus can lead to increases in intracranial
pressure, cerebral edema, and ultimately herniation of brain tissue. Various
types of cerebral shunts are available, and they are classified by name, according to where the distal end of the shunt catheter routes CSF, or by valve type.5
Examples of different types of shunts include ventriculoatrial, ventriculopleural, and VP. Ventriculoperitoneal shunts route excess CSF from the ventricles
into the peritoneal space. Conditions that routinely require the placement of VP
shunts are listed in Table 1.
Complications resulting from VP shunt placement are common, particularly
early after placement. Following VP shunt placement, the 1-year shunt failure rate
is approximately 40%, and the 2-year shunt failure rate has been reported to be as
high as 50%.5 Complications include intraventricular hemorrhage, obstruction,
overdrainage of CSF, and infection. Among these complications, infection is one
of the most serious, often requiring prompt management.

Diana L. Wells is Assistant Clinical Professor, Department of Pharmacy Practice, Auburn University
Harrison School of Pharmacy, 1321 Walker Bldg, Auburn, AL 36849 (diana.wells@auburn.edu).
John M. Allen is Assistant Clinical Professor, Department of Pharmacy Practice, Auburn University
Harrison School of Pharmacy, and Adjunct Assistant Professor, Department of Surgery, University of
South Alabama College of Medicine, Mobile, Alabama.
The authors declare no conflicts of interest.
DOI: 10.1097/NCI.0b013e31827be1d1

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and shunt insertion performed by neurosurgeons

with limited experience.1,2,6

Table 1: Indications for Ventriculoperitoneal

Shuntsa
Hydrocephalus

Microbiology
Shunt infections are often the result of contamination of the proximal end of the shunt with
normal skin flora. Among these flora, coagulase-negative Staphylococci and Staphylococcus aureus are the most common pathogens
associated with the development of VP shunt
infection. Infections caused by these pathogens
account for 50% and 33% of all shunt infections, respectively.14,15
Timing of the infection appears to be related
to the specific microbiology of VP shunt infection. Early VP shunt infections (within weeks of
insertion and revision) are typically caused by
skin flora, such as coagulase-negative Staphylococci and S aureus. However, late VP shunt
infections (several months after insertion and
revision) are usually caused by Streptococcus
spp and gram-negative pathogens, such as
Pseudomonas aeruginosa, and occur as a direct
result of bowel perforation or peritonitis. Other
rare pathogens associated with late VP shunt infections include Candida albicans, Corynebacterium jeikeium, and Mycobacterium spp.1619
Table 2 lists additional pathogens associated
with VP shunt infections.14,16

Brain tumor (benign or malignant)

Spina bifida
Congenital aqueductal stenosis
Craniosynostosis
Dandy-Walker syndrome
Arachnoid cyst
Idiopathic intracranial hypertension
a

Based on data from George et al1 and Schoenbaum et al.21

Incidence and Risk Factors

for Infection
Hydrocephalus that requires the placement
of a VP shunt may occur for many reasons,
but the cause of hydrocephalus does not seem
to affect the risk for shunt infection.6 The
incidence of VP shunt infections in adults is between 1.6% and 16.7%.1,610 Such wide ranges
of infection rates are due in part to varying
definitions of shunt infections and patient
demographics reported throughout the literature. Presently, no guideline recommendations
are available for the diagnosis of a CSF shunt
infection; however, standardized approaches
have recently been proposed.11
The highest rate of shunt infection occurs
early after shunt placement or revision (eg,
within 1 month); therefore, most contamination with microorganisms is thought to occur
intraoperatively.1,10,12 The infection rate increases with the number of surgical revisions.1,6
In fact, adult patients with previous revisions
for mechanical shunt dysfunction are 3 times
more likely to develop an infection than
those who have not undergone any surgical
revisions.6 These numbers are important to
consider because an estimated 50% or more of
all patients with a CSF shunt require at least 1
surgery for revision.10,13
Some evidence also suggests that a history of
craniotomy or external ventricular drain (EVD)
prior to shunt placement doubles the risk for shunt
infection.6 Despite the limited evidence, healthcare providers can reasonably consider these
procedures as possible risk factors, given that
both procedures have the potential to introduce
microorganisms into the sterile environment of
the CSF. Other risk factors include younger age,
holes in surgical gloves, postoperative CSF leak,

Diagnosis
Initially, a VP shunt infection may not elicit
obvious neurological symptoms.20 However,
symptoms can develop when the infection
causes shunt obstruction and subsequent

Table 2: Common Pathogens Associated

With Ventriculoperitoneal Shunt
Infectionsa
Early Infection (85%
of Shunt Infection)
(Within Weeks of Shunt
Placement or Revision)

Late Infection (15% of

Shunt Infection) (Several
Months After Shunt
Placement or Revision)

Coagulase-negative
Staphylococci (ie,
S. epidermidis)50%

Pseudomonas
aeruginosa

Staphylococcus
aureus33%

Serratia marcescens

Corynebacterium

Stenotrophomonas

Propionibacterium
acnes

Candida albicans

Based on data from references 14-16.

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increases in intracranial pressure. These symptoms include headache, nausea, vomiting, and
altered mental status.
Clinical suspicion for a VP shunt infection
warrants evaluation of CSF, blood cultures, and
neuroimaging studies. Cerebrospinal fluid for
analysis should be obtained directly from the VP
shunt rather than via lumbar puncture, if possible, and should include white blood cell (WBC)
count with differential, glucose, and protein
concentrations. Gram stain and CSF culture
should also be performed because identification
of pathogens is necessary for successful directed
antibiotic therapy.
A positive CSF analysis will yield elevations in WBC count (1000-5000/mcL), with
a high percentage of neutrophils (80%) and
protein concentration (100-500 mg/dL). Cerebrospinal fluid glucose concentrations are usually decreased (40 mg/dL). Clinicians should
note that interpretation of CSF analysis may
be more difficult in certain circumstances. For
example, traumatic lumbar puncture, generalized seizures, or intracerebral or subarachnoid
hemorrhage may cause spurious elevations in
CSF WBC count.
The use of blood cultures to help diagnose
shunt infections has been shown to yield inconsistent results. Previous studies21,22 report positive blood cultures in only 23% of VP shunt infections, whereas 95% of ventriculoatrial shunt
infections produced positive blood cultures.
Neuroimaging is useful to identify ventriculitis and obstruction of CSF. Abdominal imaging can also be used to help identify blockage
of the distal end of the shunt. Recently more
standardized diagnostic criteria for definite and
probable shunt infections have been proposed
and are summarized in Table 3.11

Table 3: Overturfs11 Diagnostic Criteria for

Ventriculoperitoneal Shunt Infectiona
Definite Shunt Infection

Probable Shunt
Infection

Compatible clinical signs

and symptoms

Compatible signs and

symptoms

PLUS
Isolation of bacterial
pathogen from device
puncture, lumbar
puncture, or other
significant site
(overlying shunt
wound, cellulitus, or
shunt tubing)

CSF consistent with

bacterial infection
Negative blood, CSF,
and device cultures
for bacteria

Abbreviation: CSF, cerebrospinal fluid.

a
Used with permission from Overturf.11

temporary EVD if needed, culture of various sites (wound, shunt tip, CSF from valve,
ventricular CSF, lumbar CSF, and/or blood),
and treatment with intravenous and possibly
intraventricular antibiotics.
Because the distal end of a VP shunt lies
within the peritoneal cavity, the risk for infection with gram-negative bacteria is also a possibility, and empiric antibiotic choices should
include coverage for these pathogens.23,24
Systemic Antibiotics

Most VP shunt infections require treatment

with systemic antibiotics. For empiric antibiotic selection, the clinician should assume that
antimicrobial resistance is a possibility and
choose broad-spectrum coverage until culture
identification and susceptibility data are available. Current guidelines recommend combination therapy with vancomycin plus one of the
following agents: cefepime, ceftazidime, or meropenem.23 Common dosing requirements for
these antibiotics are listed in Table 4. The antibiotic choice and dosing are based on the need
for adequate penetration of the drug into the
CSF for bactericidal efficacy against the infection in the setting of meningitis.23

Treatment
Most infections arise from skin flora rather than from an abdominal source, resulting in an infection of the central nervous
system (CNS).1 Because meningitis is a
common result of VP shunt infections, a
strong emphasis on appropriate treatment
is needed.1,23,24 Although the management
of VP shunt infections is not standardized,
the Infectious Diseases Society of Americas
guidelines23 offer some direction in the treatment approach for patients with meningitis
who have a CSF shunt. The management
of the infection often involves the removal
of the infected shunt with placement of a

Intraventricular Antibiotics

In patients with infections that are difficult to

cure or in those who cannot undergo removal
of the infected shunt, the current guidelines recommend that clinicians consider direct administration of antibiotics into the ventricles.23 Note
that the specific indications for intraventricular
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Table 4: Common Intravenous Antimicrobial Treatment Regimens for Ventriculoperitoneal

Shunt Infections Based on Causative Pathogena

Microorganism

Common Intravenous
Dosing Requirements
(Normal Renal Function)

Treatment
of Choice

Treatment
Duration, d

Coagulase-negative Staphylococci
(eg, S epidermis)

Vancomycin

15 mg/kg every 8-12 h

Staphylococcus aureus

MRSA: Vancomycin

15 mg/kg every 8-12 h

10

MSSA: Nafcillin

2 g every 4 h

Ceftazidime

2 g every 8 h

Cefepime

2 g every 8 h

Meropenem

2 g every 8 h

Gram-negative bacilli (eg,

P aeruginosa)

10-14; depending on
clinical response

Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.

a
Based on information from meningitis guidelines and Tunkel et al.23,24

shunt was not removed were associated with a

significant increase in the number of subsequent
shunt revisions due to complications from the
infection (eg, blockage of the distal catheter).
On the basis of these findings, the authors concluded that the treatment combination of shunt
removal, 20 mg/d of intraventricular vancomycin, and systemic antibiotics was both safe and
effective for CSF shunt infections.25
In another case series of adult and pediatric
patients, Swayne et al26 describe their results
with a similar treatment approach to Bayston
and colleagues.25 Twenty episodes of CSF
shunt infections in 15 patients were treated
with shunt removal, placement of an EVD, and
intraventricular vancomycin (adults: 20 mg/d
[n 6]; pediatric patients: 10 mg/d [n 9]).
One of the major differences in this treatment
approach from the previous is the placement
of an EVD, which allowed both access to the
ventricle for antibiotic administration and
control of CSF pressure for the duration of
treatment. Similar to the previous study, most
patients received concomitant systemic antibiotics, including vancomycin, gentamicin, flucloxacillin, trimethoprim, and cotrimoxazole.
Antituberculosis antibiotics were also administered for 3 of the reported infections; however, the names of these antibiotics were not
reported. Interestingly, intraventricular vancomycin was the only antibiotic administered
in 4 of the study patients. All study patients,
however, had follow-up CSF samples that
were sterile and free of pus, suggesting that the
treatments led to an acute resolution of CSF
shunt infections. Staphylococcus epidermidis
was the most common pathogen identified,

antibiotic administration have not been defined.

Limited data are available for the use of intraventricular antibiotics for the treatment of VP
shunt infection in adults, and no antibiotics are
currently approved for this use by the Food and
Drug Administration. However, this practice is
used often in the clinical setting on the basis of
several case reports.18,25,26
Vancomycin is the most widely studied antibiotic for intraventricular administration in
adults. In a retrospective case series by Bayston
et al,25 50 cases of ventriculitis caused by CSF
shunt infections in pediatric and adult patients
were treated with intraventricular vancomycin.
Cerebrospinal fluid culture data revealed that all
infections were susceptible to vancomycin, and
the most commonly identified pathogen was
coagulase-negative S aureus. Doses ranged from
5 to 20 mg once daily; however, most patients
(76%) received 20 mg/d. Lower doses were primarily used in the pediatric population. Because
of the retrospective study design, the treatment
regimens were not standardized, and most patients received a combination of approaches, including intravenous, intraventricular, and oral
antibiotics in addition to shunt removal and/or
placement of an EVD. Treatment continued
up to 3 to 4 days after negative CSF cultures
were obtained. Follow-up to determine treatment success occurred between 3 months and
4 years after antibiotics were discontinued. The
overall cure rate was 66%; however, those who
received the treatment combination of shunt
removal, 20 mg of intraventricular vancomycin daily, and systemic antibiotics experienced
a 92% cure rate, and no reports of vancomycin
toxicity were noted. Infections in which the CSF
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and not all isolates were sensitive to the systemic antibiotics used, which suggests that the
intraventricular antibiotic alone was effective
in many reported cases; the authors concluded
that in uncomplicated cases of shunt infections
with gram-positive cocci, monotherapy with
intraventricular vancomycin is an effective
treatment option.26
Knudsen et al18 described their success with
intraventricular vancomycin for the treatment
of VP shunt-related ventriculitis due to Corynebacterium jeikeium in a 52-year-old woman.
After an unsuccessful treatment regimen with
intravenous vancomycin (1 g intravenously every
12 hours), the patient was subsequently treated
with shunt removal and intraventricular vancomycin (10 mg/d for 4 days), followed by oral
rifampicin and fusidic acid. The total duration
of treatment was 15 days. As of 1 year after
discharge, the patient did not experience any
relapse of infection.18
In summary, for complicated VP shunt infections (eg, meningitis), clinicians should consider
administration of intraventricular antibiotics
in addition to systemic antibiotics, preferably
after the infected shunt has been removed,
as cure rates are highest with this treatment
approach.18,2326 Both systemic and intraventricular antibiotics should be de-escalated to
target the causative pathogen on the basis of the
available culture and sensitivity data. Uncomplicated infections may be treated successfully
with intraventricular vancomycin alone if a susceptible pathogen is identified from the CSF or
drain culture.
Many other antimicrobial agents, including
aminoglycosides and colistin, have been administered intraventricularly.23 Table 5 summarizes
the recommended dosages for intraventricular
use of these agents. The optimal dosing strategy is not well established; however, maintaining trough CSF concentrations of at least 5 to
10 times the minimum inhibitory concentration of the causative pathogen is recommended.
Although no clear recommendation exists for
duration of treatment with intraventricular antibiotics, clinical signs of infection should be
resolved and negative CSF cultures should be
obtained prior to discontinuation.23,27

Table 5: Recommended Dosages of

Antimicrobial Agents Administered by
the Intraventricular Routea,b
Antimicrobial Agent

Daily Intraventricular
Dose, mg

Vancomycin

5-20c

Gentamicin

1-8d

Tobramycin

5-20

Amikacin

5-50e
5f

Polymyxin B
Colistin

10

Quinupristin/dalfopristin

2-5
5-40g

Teicoplanin
a

23

Used with permission from Tunkel et al.

There are no specific data that define the exact dose of an
antimicrobial agent that should be administered by the
intraventricular route.
c
Most studies have used a dose of 10 mg or 20 mg.
d
Usual daily dose is 4 to 8 mg for adults and 1 to 2 mg for children.
e
Usual daily dose is 30 mg.
f
Dosage in children is 2 mg daily.
g
Teicoplanin is a glycopeptide antibiotic that is used outside the
United States. Dosage of 5 to 10 mg every 48 to 72 hours was used
in one pediatric study.33
b

no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary

tract is not entered) such as CSF shunt insertion. If
a patient is allergic to cephalosporin agents, clinicians are recommended to use an alternative agent
such as vancomycin for gram-positive coverage.28
However, primary literature in support of this recommendation, specifically for CSF shunt insertion
in adult patients, is lacking.
In light of the increasing incidence of methicillin-resistant strains of S aureus, Tacconelli
et al29 compared infection rates in adult patients
who received vancomycin 1 g intravenously
over 60 minutes (n 88) versus cefazolin 1.5
g intravenously over 30 minutes (n 88) prior
to CSF shunt implantation in a prospective, randomized trial. Patients in the cefazolin group
received doses every 4 hours until surgery was
completed. By 4 weeks after the procedure in an
intention-to-treat analysis, shunt infections developed in 4 patients who received vancomycin
(4.5%) and 12 patients who received cefazolin
(13.6%) (relative risk: 0.27; 95% confidence
interval: 0.44-0.04; P .04). The duration of
postoperative hospitalization was longer (mean
SD: 38 37 vs 54 78 days, respectively; P
.03) and the mortality rate among patients with
postsurgical infections was greater (number: 0

Prophylactic Antibiotics to Aid

in Prevention of Infection
Current guidelines for the use of perioperative
antibiotics recommend cefazolin for clean procedures (ie, an uninfected operative wound in which
10

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vs 5; P .02) for those who received cefazolin. The authors reported that prior to the study
period, 39% of Staphylococci isolated from
neurosurgical infections at their institution were
methicillin resistant; however, all Staphylococci
isolated from the CNS shunt infections during
the study period were methicillin resistant. Given the lower incidence of infection, shorter hospital stay, and lower overall mortality rate from
postsurgical infections in patients who received
vancomycin, this study supports the routine use
of intravenous vancomycin rather than cefazolin prior to CNS shunt insertion for infection
prophylaxis. These findings would likely best be
applied in clinical settings of adult patients with
similar rates of methicillin-resistant Staphylococci. Currently, no other prospective, randomized studies are available to confirm the findings
of Tacconelli et al.29
Intraventricular antibiotic administration
also has been evaluated for prophylaxis of
CNS shunt infections. In a retrospective study
of adult patients who had undergone CNS
shunt implantation for hydrocephalus, Ragel
and colleagues12 compared the risk of shunt
infections among groups of patients who had
received various methods of antibiotic prophylaxis. A total of 802 procedures for shunt placement were performed in 534 patients during the
study period. All patients received intravenous
antibiotic prophylaxis with 1 to 2 g of cefazolin or 1 g of vancomycin prior to skin incision,
with doses typically continued for 24 hours
after the procedure. In addition, some patients
received intraventricular antibiotic prophylaxis.
Patients were observed for 90 days following
shunt implantation to evaluate the incidence of
infection. The authors compared outcomes for
4 groups of patients: group 1, 4 mg of intraventricular gentamicin (before May 16, 1999);
group 2, 4 mg of intraventricular gentamicin
plus 10 mg of intraventricular vancomycin (after May 16, 1999); and 2 control groups who
did not receive intraventricular antibiotic prophylaxis (groups 3 and 4: before and after May
16, 1999, respectively). Patients who received
both intraventricular gentamicin and vancomycin had significantly fewer infections than patients in all other groups (percentage of patients
with infections in groups 14 were 5.45%,
0.41%, 6.21%, and 6.74%, respectively). No
decrease in infection rate was observed in patients who received only intraventricular gentamicin; therefore, the authors concluded that the
combination of intraventricular gentamicin and

vancomycin was an effective method to prevent

CNS shunt infection.12
Whether antibiotic prophylaxis for VP shunt
placement should be routinely used in adults is
debatable, given the lack of well-controlled studies and guideline recommendations. A Cochrane
review from 2006, which evaluated trials involving all age groups, indicated a significant difference in favor of systemic antibiotic prophylaxis
for up to 24 hours following the placement of
internal CNS shunts.30 Clinicians are advised to
administer antibiotic prophylaxis for VP shunt
insertion; however, well-controlled trials evaluating the efficacy of this practice in preventing
infections are needed.
Another method of infection prevention is using antibiotic-impregnated shunts, a practice that
has been evaluated in several studies.3032 The efficacy of antibiotic-impregnated shunts has not
been consistently demonstrated; therefore, the
use of these devices is not the standard of care.
Conclusion
The appropriate diagnosis, treatment, and prevention of infections are important elements to
optimize care for adult patients with VP shunt
infections. In the setting of CSF shunt infections, objective information from the patients
physical examination and available culture
data should be used to guide treatment. Initial
systemic antibiotic selection should cover a
broad range of pathogens, followed by de-escalation of antibiotics once the microorganism
is identified. The best treatment results occur
when antibiotics are administered in addition
to device removal. Certainly, further studies are
needed in this patient population to determine
the most appropriate treatment approach.
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