Evidence based clinical practice guideline of fever of
uncertain source. Outpatient evaluation and management for children 2 months to
36 months of age.
SOURCE(S):
Cincinnati (OH): Children's Hospital Medical Center (CHMC); 2000. 10 p. [36
references]
MAJOR RECOMMENDATIONS:
Evidence strengths are given in brackets. Definitions of evidence grades are
repeated following the recommendations.
Clinical Assessments
The Telephone Encounter
1.
When contacted by
telephone, it is recommended that a practitioner consider physically assessing
any febrile child when verbal descriptions are unclear and the degree of
illness uncertain.
Temperature and Fever
2.
Fever is usually
defined as a temperature of at least 100.4 degrees F (38 degrees C) rectally
(see Table 1 in the original guideline document for definitions used in the
guideline). Although rectal temperatures are more accurate, it is recommended
that a practitioner give credence to a parent's verbal report of a child's
fever measured by any method, including when detected only by touch. A fever
detected only by touch is reported to have a sensitivity of 84% and specificity
of 76% [Evidence Grade: C].
Assessing the Degree of Illness
3.
Both subjective
and objective measures are recommended to estimate the degree of illness.
·
Note
1: The following features are included in
the objective Yale Observation Scale. They are recommended for consideration in
this assessment to supplement practitioners’ subjective impressions (see Table
2 in the original guideline document for the Yale Observation Scale) [Evidence
Grade: A, C].
·
Cry quality
·
Reaction to
parent
·
State of alertness
·
Color
·
Hydration
·
Interactive
behaviors
·
Note
2: The sicker a febrile child appears, the
more likely the fever is associated with a serious bacterial infection
[Evidence Grade: A, C].
|
Well appearing |
<3% chance of serious
bacterial infections |
|
Ill appearing |
26% chance of serious bacterial
infections |
|
Toxic |
92% chance of serious bacterial
infections |
·
Note
3: Response to antipyretics is not a
reliable predictor of illness severity [Evidence Grade: S, E].
Identifying Overt Focal Infections
History
4.
It is recommended
that history be targeted to determine the child's immunization status and
exposures to known infectious agents. This information, with knowledge of
disease prevalence in the community, will help establish the likelihood of
specific causes of fever, and particularly those of viral origin.
·
Note
1: Less than 1 out of 100 viral infections
is associated with a bacterial infection [Evidence Grade: C, D].
5.
It is recommended
that history also be targeted to determine if behavioral changes caused by some
focal infections have been observed. These include, but are not limited to, the
ear pulling of otitis media, coughing of pneumonia, vomiting of
gastroenteritis, or crying with voiding associated with some urinary tract
infections.
Physical Examination
6.
Because occult
bacteremia can occur with focal infections, it is recommended that when a
source of infection is identified on physical examination, further evaluations
be considered whenever the practitioner judges that focal findings are
insufficient to explain the degree of the child's fever and illness.
Identifying Occult Focal Infections
7.
Using current
technology and evidence, there are no perfect methods for detecting all
possible occult infections. There also are no methods for identifying with
absolute certainty which specific child is among the very few with a serious
bacterial infection. It is recommended that the extent of evaluation to
determine if a particular child has an occult infection, be based in part on
each individual practitioner's level of comfort with the child's degree of
illness. These approximations result from subjective and objective physical
findings as supplemented by selected laboratory results. In addition, it is
appropriate to include in the decisions a family's apparent tolerance for risk,
the likelihood that identification of the source of fever will modify
management, and the likelihood of good outpatient follow-up [Evidence Grade:
Local expert opinion].
Urinary Tract Infections (UTIs)
8.
When evaluating
infants presenting with fevers of uncertain source, it is recommended that a
practitioner have a low threshold for obtaining a urinalysis and urine culture
using sterile collection technique [Evidence Grade: C]. This recommendation is
strongest for the youngest infants. It also applies to older children with
clinical signs and symptoms suggesting a urinary tract infection.
·
Note
1: The prevalence of urinary tract infections
in infants and young children 2 months to 2 years of age who have no fever
source evident from history or physical examination is estimated to be about 5%
[Evidence Grade: E, S].
·
Note
2: Consistent clinical findings range from
being generally nonspecific in the infant, to very evident voiding dysfunction
in the older child (see Table 3 in the guideline document for clinical signs
and symptoms of urinary tract infection).
·
Note
3: The prevalence of urinary tract
infection in febrile girls age 2 months to 2 years is more than twice that in
boys (relative risk, 2.27). The prevalence of urinary tract infection in girls
younger than 1 year of age is 6.5%; in boys, it is 3.3%. The prevalence of
urinary tract infection in girls between 1 and 2 years of age is 8.1%; in boys,
it is 1.9%. The rate in circumcised boys is low, 0.2% to 0.4%. The rate in
uncircumcised boys is 5 to 20 times higher than in circumcised boys [Evidence
Grade: E, S].
9.
It is recommended
that any positive urinalysis result be considered consistent with a presumptive
diagnosis of urinary tract infection and an indication to initiate antibiotic
therapies and other measures fully described in the Children’s Hospital Medical
Center guideline titled "Evidence Based Clinical Practice Guideline for Patients 6
Years of Age or Less with a First Time Acute Urinary Tract Infection"
(March, 1999).
·
Note
1: Any one of the following study results
defines a positive urinalysis. These tests have sensitivities varying between
30-50% and specificities of 75-85%. A positive culture on urine collected using
sterile technique remains the only standard for diagnosing a definite urinary
tract infection [Evidence Grade: C].
·
Positive nitrite
screen.
·
Positive
leukocyte esterase.
·
Positive
microscopic examination. Positive if >10 white blood cells/hpf (spun sample)
or organisms visible in unspun sample or on Gram stain. More sensitive and
specific than other urine screening tests but not readily available [Evidence
Grade: C].
Pneumonia
10.
Pneumonia is
seldom occult. It is recommended that pneumonia be considered when a fever
exceeds 39 degrees C (102.2 degrees F) or a white blood cell count exceeds
20,0000 mm3 [Evidence Grade: C].
·
Note
1: In children with lower temperatures and
cell counts, the absence of respiratory distress, tachypnea, rales (crackles),
or decreased breath sounds reduces the likelihood of pneumonia [Evidence Grade:
Canadian guideline].
·
Note
2: Age is a predictor of the cause of
pneumonia. Viral pneumonia is most common during the first 2 years of life
[Evidence Grade: Canadian guideline].
·
Note
3: Chest x-rays do not often help in the
choice of appropriate pneumonia therapy [Evidence Grade: C].
·
Note
4: Pneumonia and bacteremia are
infrequently associated (<3%) [Evidence Grade: C].
Bacterial Gastroenteritis
11.
Gastroenteritis
due to any cause is rarely occult and almost always signaled by some
combination of diarrhea and vomiting.
·
Note
1: Rotavirus is the most common cause of
acute gastroenteritis in children [Evidence Grade: S, E].
·
Note
2: Bloody or mucoid stools usually herald
bacterial gastroenteritis. There is also increased likelihood if there is a
history of foreign travel or occurrence during a specific pathogen community
outbreak [Evidence Grade: S, E].
12.
Typical
gastroenteritis usually responds well to supportive care. The management and
specific recommendations for children with gastroenteritis are detailed in the
Children’s Hospital Medical Center guideline titled "Evidence Based Guidelines and Recommendations for the
Community Evaluation and Medical Management of Children with Acute
Gastroenteritis" (1997).
Meningitis
13.
Although
bacterial meningitis is sometimes occult in the ill-appearing febrile infant or
very young child, bacterial meningitis is usually suspected by clinical exam
(e.g., neck stiffness, lethargy, vomiting), and diagnosed by lumbar puncture
and the characteristics of the spinal fluid.
Identifying Occult Bacteremias
14.
It is recommended
that febrile children be assessed to approximate their risk of being one of the
<3% with occult bacteremia [Evidence Grade: C].
·
Note
1: Risks are low but modified by height of
fever and patients age. The risk for occult bacteremia is increased if more
than one risk factor is present [Evidence Grade: A, C].
See the original guideline document for a table of
fever as a predictor of occult bacteremia and a graph of age as a predictor of
pneumococcal disease in a febrile child.
Laboratory Studies and Detection of Occult Bacteremia
15.
In spite of well
appearance, a small proportion of febrile children might have bacteremia, it is
not always necessary to obtain laboratory studies immediately for children
appearing well and with clinical characteristics consistent with a low risk for
bacteremia. If the family understands, agrees, and has the resources to assure
medical follow-up, a low risk child might be considered a candidate for
observation at home with daily reassessments until the fever resolves [Evidence
Grade: D, S, E, Local expert opinion].
16.
When a child
appears ill, or there is any uncertainty about a child’s condition or risk
status, laboratory studies are recommended. Studies strongly recommended for
consideration include urinalysis, sterile urine culture, complete blood count,
white blood cell count, and absolute neutrophil count [Evidence Grade: S, E,
Local expert consensus] (see the original guideline document for a graph of
white blood cell count as a predictor of occult bacteremia).
·
Note
1: A white blood cell count of
>15,000/mm3 raises risk for bacteremia to 3-4%. If >20,000/mm3,
the risk is 8-10%.
·
Note
2: An absolute neutrophil count is more
sensitive and specific than a white blood cell or absolute band count for
occult bacteremia detection. An absolute neutrophil count of >10,000/mm3
raises risk, to 8-10% [Evidence Grade: A, C].
17.
Because 6% to 10%
of children with bacteremia may develop serious bacterial infections, it is
recommended that a blood culture also be considered especially if the child is
ill appearing or the degree of illness is uncertain. This recommendation is
particularly strong if antibiotic therapy is to be started.
·
Note
1: Blood culture of a single large blood
volume is more likely to grow organisms than multiple cultures on smaller
volumes [Evidence Grade: S, E, C].
18.
There is no
published evidence demonstrating that chest x-rays, stool cultures, and lumbar
puncture are helpful as "routine" studies. No specific
recommendations are made other than to consider these studies when there are
specific indications that the child is likely to have occult or complicated
pneumonia, gastroenteritis, or meningitis [Evidence Grade: S, E].
Treatment for Occult Bacteremia
19.
Children who
appear well, are judged to be at sufficiently low risk to preclude the need for
laboratory studies, and have a high likelihood of excellent follow-up can often
be considered candidates for observation at home without starting antibiotic
therapy [Evidence Grade: Local expert opinion].
20.
If because of
history, physical, and laboratory assessments, a child is judged to be at high
risk of being among the <3% of febrile children with occult bacteremia,
starting empiric antibiotic therapy is considered a reasonable option after
obtaining appropriate samples for culture [Evidence Grade: C, Local expert
opinion].
·
Note
1: This recommendation is strongest for
ill appearing children pending clinical responses and return of bacterial
culture results. This is especially recommended for those with white blood cell
count >15,000/mm3 or an absolute neutrophil count >10,000 /mm3.
·
Note
2: Although complications are rare and up
to 75% of occult pneumococcal bacteremia resolve spontaneously, children with
occult bacteremia and treated with antibiotics clinically improve earlier and
are less likely to be bacteremic at follow-up. An element of uncertainty is
acknowledged, however, and it is estimated that a practitioner would need to
treat 19 patients with suspect bacteremia for each patient subsequently
documented to have actual bacteremia [Evidence Grade: C, S, E, Local expert
opinions].
·
Note
3: A decision to use antibiotics and the
specific choice of antibiotic must be balanced against the increasing emergence
of bacterial resistance. Also, in spite of a prevalent practice of starting
empiric oral or parenteral antibiotics in febrile patients to try to prevent
complications, the efficacy for this practice has never been documented in a
randomized controlled fashion [Evidence Grade: M, E, S].
21.
Based on the 90%
predominance of Streptococcus pneumoniae
as a likely organism, it is recommended that initial antibiotic choices
preferentially include only amoxicillin or ceftriaxone, or both in combination.
There are no consistent evidences that one or the other of these choices is
more efficacious [Evidence Grade: A].
Note: See the original guideline document
for a table of antibiotic dosing, and a discussion of the issue of resistance
and the use of "high dose" amoxicillin.
·
Note: For patients with likely allergies to the preferred antibiotics,
no alternative antibiotics have been documented to be more efficacious. It is
recommended that alternative drug choices be based on bacterial cultures and
antibiotic sensitivities. Consultation with a specialist in pediatric
infectious diseases might also be considered.
22.
It is recommended
that deferring antibiotic treatment pending a period of observation at home
also be considered a valid management option for selected patients who look
well, have normal laboratory studies, and with high likelihood of excellent
follow-up.
23.
It is recommended
that, with the exception of special situations, if a decision is made to treat
with antibiotics, the therapy be discontinued if cultures are reported as being
negative.
24.
If a blood
culture is returned as being positive or fever is persistent, reexamination is
recommended to reassess for the possibility that bacteremia was due to a
previously undetected focal infection such as meningitis. It is recommended
that the decision about whether to start or change antibiotics and whether to
follow the child as an inpatient or outpatient be based on the current
condition of the child and the organism isolated [Evidence Grade: S, E].
Evidence
Based Grading Scale:
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
E: Expert opinion or consensus
F: Basic laboratory research
S: Review article
M: Meta-analysis
Q: Decision analysis
L: Legal requirement
O: Other evidence
X: No evidence
Edward E.
Rylander, M.D.
Diplomat
American Board of Family Practice.
Diplomat
American Board of Palliative Medicine.