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Effect of Rapid Diagnosis of Influenza Virus Type A on the Emergency Department Management of Febrile Infants and Toddlers
Vidya Sharma, MBBS, MPH;
M. Denise Dowd, MD, MPH;
Andrew J. Slaughter;
Stephen D. Simon, PhD
Arch Pediatr Adolesc Med. 2002;156:41-43.
ABSTRACT
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Background Evidence shows that the rapid detection of influenza using an enzyme-linked
immunosorbent assay decreases antibiotic use in the treatment of pediatric
patients. To our knowledge, the effect on other diagnostic testing in an emergency
department (ED) has not been examined.
Objective To determine the effect of rapid diagnosis of influenza virus type A
on the clinical management of febrile infants and toddlers in a pediatric
ED at an urban children's hospital.
Materials and Methods A retrospective review of ED records from an electronic database was
performed. All children 2 to 24 months of age, with a temperature higher than
39°C who had a positive influenza virus type A test result using an enzyme-linked
immunosorbent assay from November 1, 1998, through April 30, 2000 (n = 72),
were included in this study. Two groups were compared—those who had
positive test results reported before discharge from the ED (early diagnosis)
and those who had positive test results after discharge (late diagnosis).
Results Forty-seven patients (65%) were in the early diagnosis group and 25
(35%) in the late diagnosis group. The groups were similar for age, temperature,
and triage category. Fewer patients in the early diagnosis group received
ceftriaxone sodium compared with those in the late diagnosis group (2% vs
24%, P = .006); there were fewer urinalyses (2% vs
24%, P = .006) and complete blood cell counts performed
(17% vs 44%, P = .02).
Conclusions Rapid confirmation of influenza virus type A infection seems to decrease
ancillary tests and antibiotic use in febrile infants and toddlers in the
ED. A prospective study with a larger group is needed to confirm these findings.
INTRODUCTION
INFLUENZA VIRUS type A (IVTA) infections are a common cause of illness
in infants and children in the winter. Attack rates in healthy children are
estimated to be between 10% and 40% each year.1
Approximately 1% of young children with IVTA are hospitalized, rates in children
with chronic diseases are higher.2 Influenza
virus type A infection may mimic bacterial sepsis in early infancy owing to
its nonspecific presentation with fever and/or irritability.3
To distinguish viral infections from bacterial infections, diagnostic testing,
including chest radiographs, urinalysis (UA) and culture, complete blood cell
count (CBC), and blood culture and cerebrospinal fluid examination are frequently
performed in children younger than 24 months. Additionally, the empirical
use of antimicrobial agents and hospitalizations are not uncommon. Various
diagnostic guidelines for fever without focus have been studied but none include
the use of a rapid viral test.4 A rapid, specific
test for viral infection has the potential to reduce the amount of diagnostic
testing, empirical antibiotic usage, and decrease hospitalization. This should
ultimately result in a reduction of complications associated with empirical
treatment as well as financial cost.
Neuraminidase inhibitors, such as zanamivir and oseltamivir phosphate,
with activity against both influenza virus types A and B, have been approved
by the Food and Drug Administration for influenza.4-5
When started early in the course of the disease amantadine hydrochloride and
rimantadine hydrochloride have been shown to decrease the severity of symptoms
in patients with influenza.6-7
For antiviral therapy to have an effect on the course of the disease, a rapid,
specific diagnosis, shortly after the onset of the disease is essential.
Rapid diagnostic testing for the detection of IVTA is available. The
rapid detection of influenza virus type A infection by enzyme-linked immunosorbent
assay (ELISA) is a sensitive and specific test compared with a viral culture
for the diagnosis of IVTA in children.8-9
The effect of rapid diagnosis of viral infections on patient care has been
studied for enterovirus and IVTA infections.10-11
Rapid diagnosis of enteroviral infections was shown to decrease unnecessary
diagnostic and therapeutic interventions such as the administration of intravenous
antibiotics, chest radiographs, and computed tomographic scans.10
A study by Noyola and Demmler11 demonstrated
that rapid diagnosis of influenza virus type A resulted in a positive effect
on medical management by decreasing antibiotic use both in the emergency department
(ED) and for hospitalized pediatric patients.
Febrile infants and toddlers are a sizable proportion of patients evaluated
in pediatric EDs. During influenza epidemics the numbers of infants and toddlers
evaluated for fever increases dramatically. For a test to have an effect on
clinical management in the ED, the result should be available at the time
diagnostic and treatment decisions are made. The virology laboratory at the
study hospital established a rapid test for IVTA in 1998. During the 1998-1999
influenza season, this test was unavailable as a 24-hour test but rather as
a convenience test that was performed on weekdays between 8 AM and 4 PM. During
the 1999-2000 season, the test was available around the clock 7 days a week
with results provided to the physician within 2 hours.
This study was undertaken to determine the effect of this procedural
change in rapid IVTA testing on the clinical management of febrile infants
and toddlers, specifically other diagnostic testing performed and treatment
with broad-spectrum antibiotics. We compared patients having a confirmed diagnosis
of IVTA infection before discharge from the ED (early diagnosis) to patients
in whom the diagnosis was confirmed after discharge from the ED (late diagnosis).
MATERIALS AND METHODS
DATA COLLECTION
This study was exempted from review by the pediatric institutional review
board at the University of Missouri at Kansas City because no patient identifiers
were collected and clinical care was not affected. The setting was an urban
children's hospital ED with an annual census of 55 000. Approximately
2000 febrile infants and toddlers are evaluated in the ED each year. Clinical
data were accessed through the central data repository at the hospital where
all patient encounters data are stored. Electronic medical records of all
infants and toddlers 2 to 24 months old, with a temperature higher than 39°C,
who presented to the ED or the urgent care clinic between November 1, 1998,
through March 30, 1999, and November 1, 1999, through March 30, 2000, were
retrospectively identified. All patients who had an ELISA test to detect IVTA
and tested positive were included herein. The decision to perform an IVTA
test was made at the discretion of the individual treating physician; no specific
set of criteria was used, including the timing of the testing during the ED
visit. The hospital laboratory used the same ELISA to detect IVTA infection
in each of the 2 study periods. The test used was commercially available (Directigen
FLU-A; Becton Dickinson, Franklin Lakes, NJ). Using cell culture and blocking
results as the reference, the manufacturer estimated this test to have an
overall sensitivity of 91% and a specificity of 95%.8
Variables recorded included triage status (emergent, urgent, or nonurgent);
date and time the patient was seen; date and time the influenza virus type
A test was ordered; date and time of the influenza virus type A test results;
other ancillary tests ordered such as UA, CBC, and chest radiographs with
their results; whether the patient was admitted to the hospital; length of
inpatient stay; and total charges.
DATA ANALYSIS
Data were first analyzed using descriptive methods. All of the categorical
variables were tested using the Fisher exact test. All continuous outcomes
were compared using an independent samples t test.
All tests were 2-sided at an  level of .05. Statistical analysis was
conducted using SPSS Version 9 for Windows (SPSS Inc, Chicago, Ill).
RESULTS
During the 2-year study period there were a total of 2772 infants and
toddlers between ages 2 and 24 months with a temperature of higher than 39°C
who presented to the ED for urgent care. Of these 183 (6.6%) were tested for
IVTA, a total of 72 infants and toddlers had a positive test result and were
included in the study; 47 (65%) had test results available before discharge
from the ED (early diagnosis) and 25 (35%) had test results available after
discharge (late diagnosis). For all patients, the mean age was 9 months; mean
temperature, 39.8°C; and the white blood cell count ranged from 5200 to
18 300 cells/µL (mean of 11 800 cells/µL). Early and
late diagnosis groups did not significantly differ for age, triage categories,
temperature, white blood cell count, chest radiographs performed, mean (SD)
length of stay in the ED 187 (58.9) vs 204 (80.6) minutes, mean (SD) charges
$650 (339.5) vs $747 (337.6), or admission to an inpatient unit.
As given in Table 1 fewer
patients in the early diagnosis group received ceftriaxone sodium compared
with the late diagnosis group (2% vs 24%, P = .006).
Similarly, fewer UAs (2% vs 24%, P = .006) and CBCs
(17% vs 44%, P = .02) were performed in the early
vs late diagnosis groups.
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Diagnostic Tests Ordered and Antibiotics Given to 72 Infants and Toddlers
Having the Diagnosis of Influenza Virus Type A Infection
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COMMENT
Managing febrile infants and toddlers in EDs or urgent care is associated
with costly and painful interventions, which may be decreased if a definitive
diagnosis is readily available. Test results must be available at the time
clinical decisions are made, for the ED, on a 24-hour basis. This study confirms
a decrease in antibiotic and ancillary test use in febrile infants and toddlers
presenting to the ED where the diagnosis of IVTA infection was confirmed rapidly.
We show that a preliminary diagnosis of influenza virus type A, when
an obvious bacterial source was not present, did decrease antibiotic use.
Patients in whom the diagnosis of influenza was confirmed before ED discharge
were less likely to receive ceftriaxone therapy than those with the same disease
but in whom the diagnosis was not confirmed before ED discharge. This suggests
that physician decision making was influenced by the test results. Bacterial
and viral infections have been shown to coexist.12
But, the incidence of serious bacterial infections in infants and toddlers
with other viral infections such as viral syndromes and bronchiolitis with
respiratory syncytial virus infection has been shown to be low.13-16
We observed statistically significant differences in the use of ancillary
tests such as UAs and CBCs. Data from the rapid diagnosis of enteroviral meningitis
by enteroviral-specific reverse transcriptase polymerase chain reaction suggest
that the test must be ordered early in the evaluation process to have a maximum
effect on patient management.10 In busy EDs
many tests may be ordered at the same time; however, further reductions are
likely in ancillary test use, such as chest radiographs, if the IVTA tests
are ordered early in the evaluation process in the IVTA season. A cost analysis
of enteroviral-specific reverse transcriptase polymerase change reaction demonstrated
significant cost savings especially if the test was limited to use in the
enteroviral season.17 The length of stay in
the ED was not different between the groups whose conditions were diagnosed
prior to discharge compared with those whose conditions were diagnosed later,
which suggests that the test did not prolong the time the infant spent in
the ED.
This observational study has clear limitations. Most importantly, the
group of children being tested was chosen at the discretion of the physician
and not randomly selected. While it seems early testing has the potential
of decreasing antibiotic usage and ancillary testing, future studies examining
a comparison of randomly selected children will be necessary to generalize
these findings. Other limitations include the small sample size. This study
had only limited power to detect large effects. For an outcome such as chest
radiograph use, which had 68% use in the patients in the late diagnosis group,
we would have 81% power for detecting a decline to 31% in the early diagnosis
group. Thus, this research design only had enough precision to detect very
large differences between the 2 groups. Another limitation is the retrospective
nature of the study, because of this, it cannot be concluded that the positive
test result was the sole cause of the significant reductions in antibiotic
and ancillary tests that we observed; other factors may have played a role
in management. We did not examine the effect of the influenza test on other
aspects of the patients' management, for example, other viral tests done or
the use of intravenous fluids. Lastly, we only examined the use of ceftriaxone
but not other broad-spectrum antibiotics. We believe this is unlikely to introduce
bias since in our ED only ceftriaxone is used in the vast majority of cases
and it is our impression that this practice did not change during the study
period.
CONCLUSION
We demonstrated decreases in ceftriaxone therapy use and the number
of UAs and CBCs ordered in a group of febrile infants and toddlers with IVTA
infection presenting to the ED in whom the results of the ELISA for IVTA was
available before discharge from the ED compared with infants and toddlers
for whom the test results were available later. A prospective larger study
is needed to confirm our findings and to test the effects on other factors
such as patient satisfaction with care and return visits to the ED or primary
care physician offices.
| What This Study Adds
Influenza virus type A infections, a common cause of illness in children
in the winter, may mimic bacterial sepsis in young infants and toddlers owing
to its nonspecific presentation with fever and irritability. Rapid diagnosis
of influenza virus type A has been shown to decrease antibiotic use in both
ED-treated and hospitalized pediatric patients.
This study confirms decreased antibiotic use in febrile infants and
toddlers presenting to the ED who have rapid confirmation of influenza virus
type A infection. In addition, this study also found decreased empirical testing
of infants and toddlers who present with fever without a focus. A larger prospective
study is needed to confirm these results. Should this be confirmed, future
guidelines for fever without a focus in infants and toddlers may need to consider
the use of rapid viral diagnostic tests to decrease empirical testing and
antibiotic use in these infants and toddlers.
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AUTHOR INFORMATION
Accepted for publication August 30, 2001.
Corresponding author and reprints: Vidya Sharma, MBBS, MPH, Department
of Pediatrics, Children's Mercy Hospital, 2401 Gilham Rd, Kansas City, MO
64108 (e-mail: vsharma{at}cmh.edu).
From the Departments of Pediatrics (Drs Sharma, Dowd, and Simon) and
Information Services (Mr Slaughter), Children's Mercy Hospital, Kansas City,
Mo; and the University of Missouri School of Medicine at Kansas City (Drs
Sharma, Dowd, and Simon).
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