Perspective-Research.indd

To assess adherence to real-time changes in guidelines

for inﬂ uenza diagnosis and use of oseltamivir during the

2009 inﬂ uenza A(H1N1) pandemic, we reviewed medical

records of patients with conﬁ rmed or suspected inﬂ uenza-

like illness (ILI) and those with no viral testing in a large

Los Angeles (California, USA) hospital. Of 882 tested

patients, 178 had results positive for inﬂ uenza; 136 of the

remaining patients received oseltamivir despite negative

or no results. Oseltamivir use was consistent with national

recommendations in >90%. Of inpatients, children were

less likely than adults to have ILI at testing and to receive

oseltamivir if ILI was found. Of outpatients, children were

more likely to have positive test results; 20% tested did not

have ILI or other inﬂ uenza signs and symptoms. Twenty-

ﬁ ve of 96 test-positive patients and 13 of 19 with lower

respiratory tract disease were, inappropriately, not treated.

Variations between practice and national recommendations

could inform clinical education in future inﬂ uenza seasons.

n April 2009, the novel inﬂ uenza A(H1N1) pandemic

inﬂ uenza virus (inﬂ uenza A[H1N1]pdm09) was

identiﬁ ed as the cause of inﬂ uenza outbreaks. Inﬂ uenza

Evaluation of Diagnostic and

Therapeutic Approaches for

Suspected Inﬂ uenza A(H1N1)pdm09

Infection, 2009–2010

Vini Vijayan, Jennie Jing, and Kenneth M. Zangwill

RESEARCH

1414 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012

Author afﬁ liation: Los Angeles Biomedical Research Institute at

Harbor–UCLA Medical Center, Torrance, California, USA

DOI: http://dx.doi.org/10.3201/eid1809.111564

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the

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This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation

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Release date: August 10, 2012; Expiration date: August 10, 2013

Learning Objectives

Upon completion of this activity, participants will be able to:

• Analyze the use of diagnostic testing in cases of influenza-like illness

• Evaluate the use of antiviral medications for outpatient cases of influenza-like illness

• Evaluate the use of antiviral medications for inpatient cases of influenza-like illness

• Assess the care of patients with influenza-like illness and lower respiratory tract infections

CME Editor

Carol E. Snarey, MA, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Carol E. Snarey, MA, has disclosed no

relevant financial relationships.

CME Author

Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of

California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

Authors

Disclosures:

Vini Vijayan, MD;

and

Jennie Jing, MS,

have disclosed no relevant financial relationships.

Kenneth Zangwill, MD,

has disclosed the following relevant financial relationships: served as an advisor or consultant for Merck & Co. Inc.; received grants

for clinical research from Novartis.

Inﬂ uenza A(H1N1)pdm09 Infection

disease caused by this strain rapidly spread, and in June

2009, the World Health Organization (WHO) declared a

global pandemic. Disease activity peaked during May–June

2009, again in October 2009, and essentially disappeared

by May 2010 (1–3). As with previous pandemics, the strain

reemerged in the United States during the subsequent

2010–2011 inﬂ uenza season and accounted for ≈25% of

characterized strains (4).

During the pandemic, the Centers for Disease Control

and Prevention (CDC) issued several guidances for

healthcare providers for the identiﬁ cation and treatment

of patients with suspected inﬂ uenza A(H1N1)pdm09

disease (Figure 1). Several rapid inﬂ uenza diagnostic tests

for identiﬁ cation of the 2009 H1N1 strain were available,

but their poor sensitivity soon became clear (5–7). CDC

recommended that the neuraminidase inhibitor oseltamivir

be used as a ﬁ rst-line treatment during the pandemic (8).

Available data suggested that the drug was clinically

effective, but only when given within <48 hours of symptom

onset (9–11). These guidelines changed during the course

of the pandemic as real-time epidemiologic, virologic, and

clinical data emerged (8,12–15).

CDC initially recommended priority use of

antiviral drugs for only hospitalized patients and those

at increased risk for inﬂ uenza-related complications.

This recommendation reﬂ ected the knowledge that most

persons infected with A(H1N1)pdm09 virus had self-

limited, mild-to-moderate disease; that commercial and

stockpiled supplies of oseltamivir were limited; and that

the development of resistance was a concern, particularly

since no other effective and easily administered antiviral

drugs were available (15–18). Questions remained,

however, with regard to the overall risks and beneﬁ ts and

appropriate dosage of the drug for very young and obese

patients. In September 2009, CDC advised that rapid

inﬂ uenza diagnostic tests be prioritized for patients who

were hospitalized or for whom a diagnosis of inﬂ uenza

could inform clinical decision making. Furthermore, CDC

reinforced the idea that presumptive treatment should be

administered to this group of patients and expanded the

target group for treatment to include outpatients with risk

factors for severe disease, even when test results were

unknown (5). Clinical judgment was clearly a key factor in

the clinical management of patients with possible A(H1N1)

pdm09 disease.

Much has been published with regard to the

epidemiology, virology, and clinical spectrum of A(H1N1)

pdm09 illness (19,20), but no information is available with

regard to diagnostic and therapeutic decision making of

physicians or their adherence to national guidelines for ill

patients. We conducted this study to evaluate the adherence

of physicians to contemporaneous national guidelines for

diagnosis and use of oseltamivir among patients with

suspected or conﬁ rmed A(H1N1)pdm09 virus infection in

the inpatient and outpatient settings.

Methods

The study population included all persons who accessed

care from May 1 to December 31, 2009, at Harbor–UCLA

Medical Center (HUMC) in Los Angeles, California.

HUMC is a 538-bed, urban, academic, teaching hospital;

it serves a diverse population, which is ≈55% Latino, 11%

Caucasian, 24% black, 4% Asian, and 4% Paciﬁ c Islander.

We conducted a retrospective cohort study to

evaluate 3 issues: 1) adherence of clinicians to national

recommendations for use of osteltamivir among patients

with suspected or conﬁ rmed inﬂ uenza virus infection; 2)

appropriateness of patient selection for diagnostic testing;

and 3) the likelihood of clinicians to prescribe antiviral drug

therapy for persons with known inﬂ uenza-like illness (ILI)

or lower respiratory tract infection (LRTI), 2 conditions for

which CDC speciﬁ cally recommended antiviral drug therapy.

For the ﬁ rst 2 objectives, we identiﬁ ed child and adult

inpatients and those seen in the emergency department with

A(H1N1)pdm09 disease by using 4 overlapping data sources,

including the following: 1) prospectively collected electronic

A(H1N1)pdm09 virus laboratory-based surveillance data

obtained by the HUMC clinical virology laboratory and

the Infection Prevention and Control Department; 2)

electronic, pharmacy-based oseltamivir utilization data; and

3) data on point-of-care testing performed in the emergency

department. These data were combined, and we reviewed the

medical records of all patients with a positive laboratory test

for inﬂ uenza in the outpatient setting and of inpatients who

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012 1415

Figure 1. Centers for Disease

Control and Prevention

(CDC) guidance during the

2009 pandemic of inﬂ uenza

A(H1N1)pdm09 disease.

LRTI, lower respiratory tract

infection.

RESEARCH

had a laboratory test that was positive for inﬂ uenza virus or

were prescribed oseltamivir. Approval for human subjects

research was obtained from the Los Angeles Biomedical

Research Institute.

We performed a comprehensive review of medical

records by using a standardized data collection instrument

to identify demographic information and clinical

characteristics of patients with the illness, including

symptoms and signs and results of viral diagnostic

testing and chest radiographs. Use of and indications for

oseltamivir, including dose and duration of use, were

recorded and, if oseltamivir was not prescribed, reasons for

not using the drug were noted. We also recorded whether

the patient exhibited risk factors for complications and

death (from a preselected list that included concomitant

cardiopulmonary, renal, liver, endocrine, blood, or

metabolic disorders; immunosuppressive conditions;

aspirin therapy; and neurologic conditions), diagnoses at

admission or discharge, and length of stay.

We deﬁ ned suspected inﬂ uenza as illness in any

patient for whom oseltamivir was prescribed by the treating

clinician. We deﬁ ned conﬁ rmed inﬂ uenza disease as illness

in a patient with a positive laboratory test result for the

virus. To evaluate adherence to guidelines, we used the

contemporaneous CDC deﬁ nition for ILI (fever and cough

with or without sore throat) and deﬁ ned severe illness as

requiring intensive care, a documented oxygen saturation

of <92%, or both.

To assess the likelihood of clinicians to prescribe

antiviral drug therapy for persons with known ILI or

LRTI, we identiﬁ ed all inpatients and outpatients with

possible upper or lower respiratory tract inﬂ uenza disease

by using International Classiﬁ cation of Diseases, Ninth

Revision (ICD-9) diagnostic codes as follows: 079.89

(viral infection), 079.99 (viral infection not otherwise

speciﬁ ed [NOS]), 460 (nasopharyngitis, acute), 462

(pharyngitis, acute), 465.8 (infectious upper respiratory,

multiple sites, acute), 465.9 (infectious upper respiratory,

multiple sites, acute NOS), 466.0 (bronchitis, acute),

466.19 (bronchiolitis, acute, due to other infectious

organism), 478.9 (disease, upper respiratory /NOS),

480.1 (pneumonia caused by respiratory syncytial

virus), 480.8 (pneumonia caused by virus), 480.9 (viral

pneumonia unspeciﬁ ed), 484.8 (pneumonia in other

infectious disease), 485 (bronchopneumonia, organism

NOS), 486 (pneumonia, organism NOS), 487.0 (inﬂ uenza

with pneumonia), 487.1 (inﬂ uenza with respiratory

manifestation), 487.8 (inﬂ uenza with manifestation),

488.1 (inﬂ uenza caused by identiﬁ ed novel H1N1

inﬂ uenza virus), 490 (bronchitis NOS), 780.6 (fever),

784.1 (pain, throat), 786.2 (cough) (21). The validity of

the ICD-9–based ascertainment was assessed by using

prospective emergency department triage ILI surveillance

data collected beginning October 21, 2009, through the

end of the study period.

From this group, we randomly selected 100 persons,

stratiﬁ ed by age (50 persons <18 and 50 >18 years of age)

by using SAS 9.2, Proc Samplesurvey (SAS Institute, Cary,

NC, USA). Using medical record review, we then identiﬁ ed

persons with ILI (deﬁ ned above) or LRTI, deﬁ ned by the

presence of at least 1 speciﬁ c lower respiratory tract sign,

including tachypnea, retractions, or hypoxia (oxygen

saturation <92%), and/or abnormal auscultatory ﬁ ndings

(crackles/crepitations or wheezing), and/or unequivocal

and abnormal radiographic ﬁ ndings.

We performed descriptive analyses of the above

variables by using SAS version 9.2. Testing of proportions

was performed by using χ

or Fisher exact test as

appropriate. All reported p values are 2-tailed and were

considered signiﬁ cant if p<0.05.

Results

Entire Cohort

We identiﬁ ed 882 patients who were tested for

inﬂ uenza virus during the study period, among whom

178 (20%) tested positive. An additional 136 received

oseltamivir but were not tested or had a negative laboratory

test result for inﬂ uenza virus. Overall, 232 (74%) of 314

patients had ILI, and 82 (26%) of 314 had a positive test

result for inﬂ uenza virus but did not meet the CDC-deﬁ ned

criteria for ILI. Of these 82, 36 (44%) had other signs or

symptoms consistent with inﬂ uenza, such as headache,

myalgia, nausea, or diarrhea. We identiﬁ ed 218 (69%)

inpatients among the 314 patients with conﬁ rmed or

suspected inﬂ uenza. Of those 314 patients, 55 (18%) were

<2 years of age, 129 (41%) were 2–18 years of age, 89

(28%) were 19 to <50 years of age, 32 (10%) were 51 to

<65 years of age, and 9 (3%) were >65 years of age. An

underlying medical condition was recognized in 88 (48%)

children (most commonly, asthma) and in 95 (52%) adults

(most commonly, immunosuppression).

Oseltamivir was prescribed for 86 (66%) of 130

children and 89 (87%) of 102 adults with ILI. Oseltamivir

was prescribed at the correct dosage and duration of

therapy for 229 (95%) of 240 patients, and 216 (90%) of

240 patients received the drug <48 hours after symptom

onset. Another 16 received the drug within 72 hours of

disease onset. Severe illness was identiﬁ ed in 132 (42%)

of 314 patients, 118 (89%) of whom received oseltamivir

(Figure 2).

Inpatients

Of 218 inpatients who received a diagnosis of or

treatment for inﬂ uenza, 107 (49%) were children, and

111 (51%) were adults. Laboratory testing was performed

1416 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012

Inﬂ uenza A(H1N1)pdm09 Infection

for 177 (81%) inpatients, and 74 (42%) were positive for

inﬂ uenza virus (Table). Oseltamivir was administered to

198 (91%) of 218 inpatients, among whom 110 (50%) had

a negative test or no laboratory testing performed. Of the

remaining 88 with a positive test result, 5 did not receive

oseltamivir because the patient refused, the patient was

“well appearing,” or patient’s onset of symptoms occurred

>48 hours before they received a diagnosis.

Of the inpatients, we identiﬁ ed 68 (64%) of 107

children and 86 (77%) of 111 adults who had ILI at the

time of laboratory testing (p<0.04). Oseltamivir was given

to 58 (85%) of the 68 children with ILI and 84 (98%) of 86

adults with ILI (p<0.02). Oseltamivir was prescribed for

145 (94%) of 155 inpatients with an underlying medical

condition and for 118 (91%) of 129 patients with severe

illness.

The median interval from illness onset to initiation

of antiviral treatment was 2 days (range 1–8). The dosage

or duration of therapy, or both, was incorrect for 11 (5%)

inpatients; for 6 inpatients, no adjustment was made for

renal insufﬁ ciency. Of those 6 inpatients, 2 had chronic renal

insufﬁ ciency after a transplant, 1 had diabetic nephropathy,

and 3 had pneumonia and renal insufﬁ ciency. Three obese

patients received a doubled dose of oseltamivir.

Receipt of the vaccine against inﬂ uenza A(H1N1)

pdm09 virus was documented in 61 (28%) of 218 patients,

but 59 (97%) of them received the vaccine at hospital

discharge. Only 1 patient had received the seasonal

inﬂ uenza vaccine before admission, and none received

vaccine at discharge.

Outpatients

We identiﬁ ed 664 patients who underwent rapid

inﬂ uenza diagnostic testing, of whom 77 (19%) of

398 children and 19 (7%) of 266 adults tested positive

(p<0.001). Twenty percent of tests were carried out on

patients without CDC-deﬁ ned ILI and for whom no other

indication was present. As noted in Figure 3, only 11%

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012 1417

Figure 2. Total number of patients

treated with oseltamivir by

category, presence of inﬂ uenza-

like illness (ILI), and disease

severity, Los Angeles, California,

USA, 2009.

Table. Patients who underwent testing or treatment for influenza by category, Los Angeles, California, USA, 2009*

Test results and treatment Inpatients† Outpatients‡

Influenza diagnostic test

Patients tested for influenza

Total 177/218 (81) 664/664 (100)

Adults 79/111 (71) 398/398 (100)

Children 98/107 (92) 266/266 (100)

Positive influenza test result

Total 74/177 (42) 96/664 (14)

Adults 18/79 (23) 19/398 (5)

Children 56/98 (57) 77/266 (29)

ILI among patients with a positive test result

Total 44/74 (59) 77/96 (80)

Adults 14/18 (78) 16/19 (84)

Children 30/56 (54) 61/77 (79)

Oseltamivir prescribed

Patients with positive influenza test result 53/74 (72) 22/96 (23)

Patients with coexisting condition 145/155(94) 15/28 (54)

Patients with severe influenza disease 118/129 (91) 0/3 (0)

Median time from illness onset to treatment, d 2 (1–8) 2 (1–5)

*Values are no./total no. (%) unless otherwise indicated. ILI, influenza-like illness.

†For inpatients who received a diagnostic test for influenza, N = 218; for outpatients who received a diagnostic test, N = 664. For inpatients who received

oseltamivir, N = 218. In the outpatient setting, study cohort was identified through diagnostic testing only. Use of oseltamivir was evaluated only among

those for whom a diagnostic test result was positive (N = 96).

RESEARCH

(73/664) of these tests were performed >2 weeks after CDC

actively discouraged their use.

Oseltamivir was prescribed for 37 (48%) of 77

outpatient children and 5 (26%) of 19 adults who tested

positive for inﬂ uenza (p>0.05), all at the appropriate

dose and duration. As recommended, 35 (83%) of 42

received the drug <48 hours from symptom onset, and

the remaining patients received the drug within 72 hours

of symptom onset. Of 54 (56%) of 96 patients who tested

positive and did not receive oseltamivir, 25 (46%) were not

treated according to CDC guidelines, and 8 (15%) refused

therapy. The reasons for not initiating oseltamivir therapy

included onset of symptoms >48 hours previously and

lack of an underlying medical condition. For 21 (39%) of

the untreated patients, we found no documentation of the

reason for withholding therapy.

We found 3 outpatients who had severe illness,

none of whom received oseltamivir, and the reasons for

withholding therapy could not be determined. Conversely,

16 (3%) of 522 patients with a negative test result received

oseltamivir. The most common reasons documented for

initiating therapy in this group included an underlying

medical condition or concomitant diagnosis of pneumonia,

ILI, or both, each consistent with CDC guidelines.

Therapy for Patients with ILI or LRTI Not

Tested for Inﬂ uenza Virus

We reviewed records of 50 randomly selected

outpatients with ICD-9 codes for ILI who were not

tested for inﬂ uenza virus. Only 3 patients (6%) received

oseltamivir (as recommended by CDC). Of the remainder

who did not receive the drug, the duration of illness

was >48 hours, the patient was “well appearing,” or no

underlying risk factors were found. The median time from

illness onset to obtaining medical attention was 3.7 days

(range 0–14 days); 22 (44%) sought treatment within

48 hours. Thirteen (26%) had an underlying medical

condition (7 children and 6 adults). For each, however,

there was an appropriate reason for withholding therapy,

per CDC guidelines.

Among 50 outpatients with ILI and LRTI, 14 (28%)

were admitted, 2 to the intensive care unit. The median

time from illness onset to obtaining medical attention

was 3 days (range 0–28 days); 31 (62%) of 50 sought

treatment >48 hours after symptom onset. Eight of

25 (32%) children and 5 (20%) of 25 adults received

oseltamivir, and 6 patients received the drug <48 hours

from symptom onset. Oseltamivir was administered to 6

(38%) of 16 patients with severe illness and to 7 (25%)

of 28 who had an underlying medical condition. The

reason for not prescribing oseltamivir was documented

in 5 charts, and the reasons included were that symptom

onset was >48 hours from the visit to the hospital and

that the patient was “well appearing.” Overall, 13 (68%)

of 19 patients with LRTI who sought treatment within

48 hours of illness onset did not receive oseltamivir as

recommended by CDC.

Discussion

We believe that this study provides useful information

with regard to the diagnostic and therapeutic behaviors of

clinicians caring for patients with possible inﬂ uenza virus

infection. Although our data reﬂ ect physician behavior

during the 2009–10 inﬂ uenza A (H1N1) pandemic, the

ﬁ ndings are likely applicable to any inﬂ uenza year because

diagnostic test performance, disease intensity, antiviral

1418 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012

Figure 3. Rapid inﬂ uenza diagnostic testing (RIDT) performed for outpatients with inﬂ uenza-like illness (ILI), Los Angeles, California, USA,

2009.

Inﬂ uenza A(H1N1)pdm09 Infection

agent resistance, and virus strain affect clinical decision

making each year.

We were interested in 2 general concepts: practice

performance when inﬂ uenza was clinically suspected

and the potential for missed therapeutic opportunities

when it was not. For the former, we found that providers’

practices were often consistent with CDC guidelines but

notable deﬁ ciencies were also identiﬁ ed. In particular, a

substantial proportion of potentially high-risk patients were

not empirically treated, and a reason to withhold therapy

could not be documented. This dynamic is similar to that

for other medical conditions for which clinical practice

guidelines are available: provider behavior at variance with

the guideline may reﬂ ect available patient-level information

or other immediate concerns (22,23). In any case, we

have identiﬁ ed potential areas for targeted education of

healthcare providers that should be supplemented by rapid

dissemination and follow-up of national guidelines if and

when they change over time.

We also found inconsistencies in the use of

antiviral drug therapy, which was often at variance with

contemporaneous guidelines. In our population, 25%

of patients who received oseltamivir did not have ILI or

another clear indication for treatment. During the pandemic,

the drug was recommended for inpatients with ILI and

outpatients with ILI and risk factors for severe illness if

they had sought treatment within 48 hours of symptom

onset (5). However, although too many outpatients without

ILI received oseltamivir, too few (32%) received the drug

despite having LRTI, a consistent indication for therapy.

For most patients with LRTI, we could not identify a

reasonable justiﬁ cation for withholding therapy. Not

surprisingly, all of these patients received antibacterial

agents, yet it remains unclear whether the clinicians actively

considered inﬂ uenza virus as a primary pathogen or risk

factor for the presumed bacterial superinfection. Inﬂ uenza

virus infection and its association with secondary bacterial

infection is well documented with inﬂ uenza A(H1N1)

pdm09 virus infection and with interepidemic disease

(24–27). Treatment with antiviral drugs in this setting

may lessen illness when superinfection exists (26,28). In

this circumstance, greater recognition of the possibility of

inﬂ uenza virus infection and use of antiviral drug therapy

may mitigate illness and lessen hospital costs (29,30).

We found that diagnostic practices were often

inconsistent with contemporaneous guidelines. Nearly one

third of patients were tested for inﬂ uenza virus, despite

the lack of ILI and ≈20% had no other indication for

which testing might otherwise be justiﬁ ed (e.g., headache,

myalgia). Previous work has shown that relatively few

patients with inﬂ uenza virus infection have systemic signs

without fever, sore throat, or cough (31). Although changes

in CDC recommendations were quickly disseminated to

hospital clinicians by management memo, email, or face-

to-face meetings, even more rapid communication and

follow-up reminders may have enhanced adherence to

guidelines.

We found that the dosage and duration of oseltamivir

were generally consistent with CDC guidelines in ≈90%

of all treated patients, and speciﬁ cally for all outpatients.

HUMC required the use of a preauthorization drug form

that noted the appropriate age- and weight-based dose;

an outpatient prescription for oseltamivir would not have

been released without a completed form. Such tools have

been shown to limit dosing errors (32,33). Also consistent

with the CDC guidelines, >90% of hospitalized patients

and patients with severe illness in our study received

oseltamivir. Among outpatients, we noted that for ≈50%,

an appropriate rationale for not providing oseltamivir was

documented in the medical record.

Among the small number of dosing errors identiﬁ ed,

>40% were related to inappropriate adjustment for renal

insufﬁ ciency. More than 90% of oseltamivir is metabolized

to oseltamivir carboxylate, 99% of which is eliminated by

renal excretion, thus requiring dosage adjustment in this

setting. Antimicrobial drug dosing errors are common

(34,35), and a failure to adjust for renal impairment is a

frequent underlying reason (36,37). Although controlled

data are not available, oseltamivir has been associated

with the development of thrombocytopenia, particularly

when renal clearance is artiﬁ cially lowered by concomitant

administration of the drug probenicid (38). Attention

should be given to patients’ renal function, particularly in

the elderly (diminished renal clearance) and in those for

whom higher doses may be recommended, such as the

severely ill or obese (8).

We identiﬁ ed clinical management differences between

how clinicians prescribed treatment for adult patients and

how they prescribed treatment for children. Children who

were inpatients were signiﬁ cantly less likely to have ILI at

the time of testing and to receive treatment for ILI. When

testing was carried out, children were also more likely to

test positive for inﬂ uenza virus than were adults, possibly

because of the higher virus load in this population. These

data also may reﬂ ect more overall testing of children,

particularly young children who are more likely than adults

to have nonspeciﬁ c signs and symptoms (lethargy, poor

feeding, abdominal pain) (39,40). In addition, infants and

young children may not articulate symptoms of ILI (e.g.,

sore throat), leading to increased nonspeciﬁ c testing and

treatment of this population.

The main strength of this study is the comprehensive

nature of case ascertainment, which included laboratory-

based information and review of all prospectively collected

logs for emergency department point-of-care testing.

However, some patients who underwent testing for

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012 1419

RESEARCH

inﬂ uenza virus may not have been noted in the outpatient

log system. We appreciate that ICD-9 code data for ILI and

LRTI may be nonspeciﬁ c, but our prospectively collected

ILI data (albeit for a limited portion of the surveillance

period) validated the temporal trends for this diagnosis

in the outpatient setting. We also did not include data

from medical outpatient (nonemergency department)

clinics where other patients with inﬂ uenza may have

been identiﬁ ed and treated, perhaps skewing our data to

those who were more ill. As a retrospective study, our

conclusions depend solely upon information documented

in the medical record, which may be incomplete. Also, the

use of an antiviral agent authorization form most likely

improved the dosing practice, as has been shown in other

settings (32,33). Last, our study population includes only a

single academic medical center and therefore may not be

representative of the region or the nation.

To our knowledge, similar studies of physician

behavior with regard to inﬂ uenza disease, and for A(H1N1)

pdm09 disease in particular, have not been reported. We

have identiﬁ ed variations in clinical practice in relation to

national guidelines that suggest potential areas of education

for future inﬂ uenza seasons.

This study was supported in part by the Los Angeles

Biomedical Research Institute and the Los Angeles County

Department of Health Services.

Dr. Vijayan performed this work as a Fellow in Pediatric

Infectious Diseases at Harbor–UCLA Medical Center. She is

currently an assistant professor of pediatrics at the University of

Florida, Gainesville. Her research interests include preventing

infections, such as inﬂ uenza and pertussis in mothers and their

infants through maternal immunization, and diagnosis and

management of travel- and migration-associated disease.

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Address for correspondence: Kenneth M. Zangwill, Harbor–UCLA

Medical Center, 1124 W Carson St, Torrance, CA 90502, USA; email:

[email protected]

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 9, September 2012 1421

The opinions expressed by authors contributing to this

journal do not necessarily reﬂ ect the opinions of the Centers for

Disease Control and Prevention or the institutions with which

the authors are afﬁ liated.