Tinea capitis is a common pediatric infection most frequently
caused by T tonsurans in the US.1-3 Systemic treatment is required
to eradicate the infection and griseofulvin has traditionally been
the antifungal therapy of choice.3 In clinical practice, effective
treatment with griseofulvin often requires higher doses and a lon-
ger duration of therapy than recommended on the package label-
ing.1,2 Effective alternative antifungal therapies that have good oral
tolerability and require a shorter course of treatment are therefore
likely to be advantageous.
This is the largest pediatric trial of terbinafine to date. Similar to
other prior studies that evaluated terbinafine tablets, terbinafine
hydrochloride granules appear to be efficacious and well-tolerated
in the treatment of tinea capitis.1-3 This new pediatric formulation,
which can be sprinkled on non-acidic food (such as pudding), may
be easier for children to consume than the tablet formulation.
A previous meta-analysis of comparative, randomized trials
of griseofulvin versus terbinafine tablets also found that terbi-
nafine was at least as effective as griseofulvin in the treatment
of Trichophyton species infections.3 However, the dosing and
duration of treatment of griseofulvin in that study were less than
what is often used in clinical practice, and the overall cure rate of
terbinafine in that trial was lower than those found in other prior
studies.1,2
Contrary to usual clinical practice, no adjunctive therapy, such
as antifungal shampoo, was utilized in the current study, which
may have affected cure rates.
Terbinafine oral granules received US approval in September
2007 to treat tinea capitis in children age four years and older.4
Recommended six-week dosing is based on body weight (<25 kg:
125 mg/day; 25-35 kg: 187.5 mg/day; >35 kg: 250 mg/day) and the
granules are available in 125 mg and 187.5 mg packets.4 Since T ton-
surans is the most common dermatophyte causing tinea capitis in
the US, terbinafine granules are a potential alternative antifungal
therapeutic option to treat tinea capitis caused by Trichophyton
species. However, if Microsporum species are identified on fungal
culture, griseofulvin is probably a better choice. Performing a fun-
gal culture on patients suspected to have tinea capitis is therefore
highly recommended to not only confirm infection, but also to
help guide appropriate therapy.
Shorter duration of therapy and the ease of administration
of terbinafine hydrochloride granules are potential advantages
compared to griseofulvin. Cost of terbinafine granules may be
less since the duration of therapy is potentially shorter than stan-
dard treatment with griseofulvin; however, the package insert for
terbinafine granules recommends baseline liver function studies
prior to treatment (baseline lab work is not usually performed in
healthy children treated with griseofulvin) which may increase the
overall cost of therapy.4
References
1. Gonzalez U, et al. Cochrane Database Syst Rev. (4):CD004685,
2007.
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Burlington, VT
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2. Friedlander SF, et al. Pediatrics. 2002;109:602-607.
3. Fleece D, et al. Pediatrics. 2004;114:1312-1315.
4. Lamasil oral granules [package insert]. East Hanover, NJ: Novar-
tis Pharmaceuticals Corp; 2007.
CRITICAL CARE
Clinical Practice
Guidelines for
Management of
Encephalitis
Source: Tunket AR, Glaser CA, Bloch KC, et al. The management
of encephalitis: clinical practice guidelines by the Infectious
Diseases Society of America. Clin Infect Dis. 2008;47(3):303-327;
doi:10.1086/589747
PICO
Question: In patients with suspected encephalitis, what is the
most appropriate diagnostic evaluation and empiric therapy?
Question type: Intervention
Study design: Practice guideline
T
he objective of this practice guideline is to provide clinicians
with evidence-based recommendations in the approach to
patients with encephalitis. The work is a consensus state-
ment by a panel of pediatric and internal medicine infectious
disease specialists and neurologists with expertise in encephalitis
who reviewed the literature published since 1996 regarding the
diagnosis and treatment of encephalitis.
In the approach to the patient with encephalitis, an attempt
should be made to establish an etiologic diagnosis. The panel
recommends cerebrospinal fluid (CSF) analysis in all cases of sus-
pected encephalitis. Culture for bacteria and fungus is indicated,
but since CSF cultures are generally of limited value in the deter-
mination of the viral causes of encephalitis, CSF should be tested
by PCR for herpes simplex virus (HSV), Epstein-Barr virus (EBV),
varicella zoster virus (VZV), the enteroviruses, and Mycobacterium
tuberculo. In patients with clinical evidence of HSV encephalitis
but negative results on initial CSF HSV PCR, repeat testing in 1-3
days may be positive.
CSF and serum antigen tests are useful in diagnosing Cryptococ-
cus neoformans while CSF and urine antigen tests are useful for
diagnosing histoplasmosis. Spirochetes such as Treponema pal-
lidum and Borrelia burgdorferi infections can be detected using
non-specific (VDRL) as well as specific antibody tests in the CSF
and serum. In the appropriate season or clinical setting, CSF can be
sent for IgM to West Nile virus, St. Louis encephalitis, and VZV.
Testing of sites outside of the nervous system may be helpful
in establishing cause for the encephalitis. While viral cultures of
the CSF are rarely useful, sputum can be sent for viral antigen
testing and culture. Biopsy of specific tissues for culture, antigen
detection, nucleic acid amplification tests (such as PCR), and his-
topathologic examination should be performed. Serologic testing
for HIV, EBV, and Mycoplasma pneumonia may be useful. In cer-
tain seasons, serologic testing should be considered for St. Louis
encephalitis virus, Eastern equine encephalitis virus, Venezuelan
equine encephalitis virus, La Crosse virus, and West Nile virus as
well as Rickettsia rickettsii, Ehrlichia chaffeensis, and Anaplasma
phagocytophilum.
CT and MRI are most frequently used to evaluate patients with
encephalitis, MRI is more sensitive and specific. MRI may show
classic findings of specific infections such as HSV encephalitis or
may be useful to exclude conditions with a clinical presentation
similar to that of encephalitis, such as acute disseminated en-
cephalomyelitis (ADEM), a disease mediated by an immunologic
response to an antigenic stimulus. Identifying ADEM is particularly
important as therapy includes high-dose steroids.
Although EEG is rarely useful in identifying a pathogen, it has
a role in identifying patients with nonconvulsive seizure activity
who are confused, obtunded, or comatose. In 80% of patients with
HSV encephalitis, a temporal lobe focus demonstrates lateralizing
periodic discharges.
Initial treatment of encephalitis should always include acyclovir
and empiric antibiotic therapy in patients with suspected bacterial
meningitis, including doxycycline if risk factors for Rickettsia or
Ehrlichia infections are present. Once an etiologic agent is identi-
fied, therapy should be targeted to that agent and other antimicro-
bial treatment discontinued.
Commentary by Susan L. Bratton, MD, MPH, FAAP
Pediatric Critical Care Medicine, Primary Children’s Medical Center, University
of Utah Health Sciences Center, Salt Lake City, UT
Dr. Bratton has disclosed no financial relationship relevant to this commentary. This commentary does not contain
a discussion of an unapproved/investigative use of a commercial product/device.
Encephalitis is defined as an inflammatory process of the brain
associated with acute neurologic dysfunction. This management
guideline is a useful and concise reference for the approach to
patients with encephalitis. Although a wide variety of agents have
been reported to cause encephalitis, most are viral. The underly-
ing cause, however, remains uncertain in approximately 50-60%
of cases despite extensive testing.1 A thorough history is needed
to reveal risk factors such as travel, exposure to mosquito or tick
bites, animal exposure, vaccination status, and patient immune
status. The season of the year and prevalence of disease in the lo-
cal community are helpful in targeting the diagnostic work-up for
encephalitis. However, no specific treatment is currently available
for most infectious causes of encephalitis.
The expert guidelines emphasize that treatment with acyclovir
be started in all patients with suspected encephalitis pending
diagnostic studies. Such treatment is associated with improved
survival and decreased morbidity from HSV and VZV but not EBV
encephalitis. Although PCR testing is very specific for HSV, it is not
100% sensitive, and for patients with clinical features suggestive of
HSV infection, repeat testing of the CSF with PCR may be indicated
if the initial testing is negative. Patients with temporal lobe findings
on MRI or seizure foci typical for HSV should be treated despite an
initial negative PCR, and expert consultation should be sought to
guide final treatment duration.
The practicing pediatrician must remain particularly vigilant
regarding neonates with fever and signs of sepsis. Among febrile
neonates with a CSF pleocytosis (either mononuclear or poly-
nuclear) approximately 1-2% have documented HSV encephalitis2
and require prompt treatment with high dose acyclovir. Reported
risk factors for neonatal HSV include maternal factors (maternal
primary HSV infection, maternal fever, vaginal delivery) and infant
factors (prematurity, postnatal HSV contact, vesicular rash, hypo-
thermia, lethargy, seizures, respiratory distress, or CSF pleocyto-
sis).3 Pediatric patients with encephalitis are at risk for brain injury
and neuropsychologic follow-up is appropriate.
Editors’ Note
The authors of this practice guideline meet the standard out-
lined in Weighing the Evidence. The important role of head MRI
to help distinguish an infectious from post-infectious etiology of
encephalitis and the automatic administration of acyclovir upon
suspicion of the diagnosis are just two of the recommendations
that head up the new guidelines for this serious inflammatory
process.
References
1. Glaser CS, et al. Clin Infect Dis. 2003;36:731-742.
2. Caviness AC, et al. J Pediatr. 2008;153:164-169.
3. Caviness AC, et al. Pediatr Infect Dis J. 2000;27:425-430.
November 2008 Downloaded
from http://aapgrandrounds.aappublications.org/ at University of Michigan on June 17, 2015
Weighing the Evidence:
Clinical Practice Guidelines
M. Paulina Velasquez, MD
Virgina A. Moyer, MD, MPH, FAAP
Where you live or which doctor you choose should not be the
primary determinant of what specific tests and treatment you get
— but often is.1 While care should vary according to the patient’s
condition and values, it should not vary based on physician “style.”
This is ever more important in the era of frequent patient handoffs.
A clinical practice guideline is a set of recommendations whose
main objective is to standardize medical practice regarding a specific
health condition. The creation of such sets promotes cost-effective
practice while helping minimize the occurrence of medical errors
and inappropriate variation in care. Guidelines are not rules set in
stone; they have to be flexible enough to allow for individualized
changes based on clinical judgment. The aim of a good guideline
is always to improve quality of care and promote optimal health
outcomes for patients.2
But…what makes a guideline “good”? This question has to be
answered whether you are looking to write a new guideline or evalu-
ating an existing guideline before introducing it into daily practice.
First, the process of creating a guideline should involve a multidis-
ciplinary team including all relevant stakeholders in order to get
adequate input from different points of view. A rigorous method of
development, including a thorough search, systematic review, and
grading of scientific evidence related to the topic is required. This is
accomplished by extracting data on the benefits, harms, and even
costs of different interventions from all important studies.3 The
information obtained is then categorized according to its quality,
and linked to each of the recommendations in the guideline. When
the evidence is limited, expert opinion often fills in the gaps so that
guidelines can be comprehensive.
As long as this process is transparent, the reader can indepen-
dently analyze the recommendations provided, and then decide if
they are applicable to any specific case.4 Keep in mind that the qual-
ity of the evidence is not the sole determinant of the strength of the
recommendation: very good evidence might exist but the trade-off
between benefits and harms may be so close that an evidence-based
recommendation one way or the other cannot be made.5
Another issue that has to be considered is the presence of edito-
rial independence and conflicts of interest. In some instances, ex-
tensive ties between guideline committees and the pharmaceutical
industry have been revealed.6 As complete avoidance of corporate
sponsorship and exclusion of experts with financial ties may be
very difficult to achieve, public disclosure of all potential conflicts of
interest should be a minimal requirement to assure that those using
the guideline can ascertain where bias might exist.4
Finally, a good guideline should not be static; it should be
reviewed and updated regularly, and a mechanism should be in
place to trigger a review if new evidence becomes available before
the scheduled update.
A guideline that has been rigorously developed by a multidisci-
plinary group should be characterized by clarity, validity, and re-
producibility. Tools that can help you assess guidelines include the
AGREE instrument, the SIGN process, and the CASP tools.6-8 These
checklists can help you determine whether the goal of moving from
best evidence to best practice is likely to be achieved. When you see
guidelines for clinical care, use the criteria discussed here to deter-
mine whether you will incorporate them into your practice.
References
1. Wennberg JE, et al. Geography and the Debate Over Medicare Reform.
Health Affairs. February 13, 2002. http://content.healthaffairs.org/cgi/
content/abstract/hlthaff.w2.96v1
2. AAP Steering Committee on Quality Improvement and Management.
Pediatrics. 2004;114:874-877.
3. Shekelle PG, et al. BMJ. 1999;318:593-596.
4. AAP Steering Committee on Quality Improvement and Management.
Pediatrics. 2008;121:643-646.
5. Guyatt GH, et al. BMJ. 2008;924-926.
6. The AGREE Collaboration. Agree Instrument. September 2001. http://
www.agreecollaboration.org/instrument/
7. Harbour R, et al. BMH. 2001;323:334-336.
8. Public Health Resource Unit. Critical Appraisal Skills Programme.
http://www.phru.nhs.uk/Pages/PHD/CASP.htm
51
 Clinical Practice Guidelines for Management of Encephalitis
AAP Grand Rounds 2008;20;50
DOI: 10.1542/gr.20-5-50

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 Clinical Practice Guidelines for Management of Encephalitis
AAP Grand Rounds 2008;20;50
DOI: 10.1542/gr.20-5-50

The online version of this article, along with updated information and services, is located on
the World Wide Web at:
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