ORIGINAL CONTRIBUTION

Emergency Department Management of

Patients With Febrile Neutropenia:
Guideline Concordant or Overly Aggressive?
Christopher W. Baugh, MD, MBA, Thomas J. Wang, BS, Jeffrey M. Caterino, MD, MPH,
Olesya N. Baker, PhD, Gabriel A. Brooks, MD, Audrey C. Reust, PA-C, and
Daniel J. Pallin, MD, MPH

ABSTRACT
Objectives: The Infectious Diseases Society of America and the American Society of Clinical Oncology recommend
risk stratication of patients with febrile neutropenia (FN) and discharge with oral antibiotics for low-risk patients. We
studied guideline concordance and clinical outcomes of FN management in our emergency department (ED).

Methods: Our urban, tertiary care teaching hospital provides all emergency and inpatient services to a large
comprehensive cancer center. We performed a structured chart review of all FN patients seen in our ED from
January 2010 to December 2014. Using electronic medical records, we identied all visits by patients with fever
and an absolute neutrophil count of <1000 cells/mm3 and then included only patients without a clear source of
infection. Following national guidelines, we classied patients as low or high risk and assessed guideline
concordance in disposition and parenteral versus oral antibiotic therapy by risk category as our main outcome
measure.

Results: Of 173 qualifying visits, we classied 44 (25%) as low risk and 129 (75%) as high risk. Management
was guideline concordant in 121 (70%, 95% condence interval [CI] = 63% to 77%). Management was guideline
discordant in 43 (98%, 95% CI = 88% to 100%) of low-risk patients versus 9 (7%, 95% CI = 3% to 13%) of
high-risk patients (relative risk [RR] = 14, 95% CI = 7.5 to 26). Of 52 guideline-discordant cases, 36 (83%, 95%
CI = 72% to 93%) involved low-risk cases with treatment that was more aggressive than recommended.

Conclusions: Guideline concordance was low among low-risk patients, with management tending to be more
aggressive than recommended. Unless data emerge that undermine the guidelines, we believe that many of these
hospitalizations and parenteral antibiotic regimens can be avoided, decreasing the risks associated with
hospitalization, while improving antibiotic stewardship and patient comfort.

(CONCERN).1 One of the most common oncologic

A gap in research on oncologic emergencies has
been identified, with the formation of the Com-
prehensive Oncologic Emergencies Research Network
emergencies is febrile neutropenia (FN) associated with
chemotherapy. FN occurs in 10%50% of patients

From the Department of Emergency Medicine, Brigham and Womens Hospital (CWB, ONB, ACR, DJP), Boston, MA; Harvard Medical School
(TW), Boston, MA; the Gastrointestinal Cancer Center, Dana Farber Cancer Institute (GAB), Boston, MA; and the Department of Emergency Medi-
cine, The Ohio State University Wexner Medical Center (JMC), Columbus, OH.
Received May 2, 2016; revision received August 8, 2016; accepted August 15, 2016.
The abstract for this study was presented at the Northeast Regional Society for Academic Emergency Medicine Regional Meeting, Worcester,
MA, March 2016.
This study was supported by a Milton Fund award at Harvard Medical School.
The authors have no potential conicts to disclose.
Authorship contributions: CWB, TW, GAB, ACR, and DJP conceived the study; CWB served as principal investigator; DJP provided statistical
advice on study design; ONB analyzed the data; JMC provided assistance with interpretation of the data; CWB, DJP, and TW drafted the manu-
script; all authors contributed substantially to its revision; and CWB takes responsibility for the paper as a whole.
Supervising Editor: D. Mark Courtney, MD.
Address for correspondence: Christopher W. Baugh MD, MBA; e-mail: cbaugh@partners.org. Reprints will not be available.
ACADEMIC EMERGENCY MEDICINE 2017;24:8391.

2016 by the Society for Academic Emergency Medicine ISSN 1069-6563

doi: 10.1111/acem.13079 PII ISSN 1069-6563583 83
84
with solid tumors and > 80% of those with hemato-
logic malignancies.2,3 These patients are typically hos-
pitalized and receive intravenous (IV) antibiotics, even
though clinically documented bacterial infections occur
in fewer than 30% of febrile episodes.2 Thus, 70%
are never found to have a bacterial infection and
might be spared parenteral antibiotics and hospitaliza-
tion, if they could be identified.
Guidelines from the Infectious Diseases Society of
America (IDSA) and American Society of Clinical
Oncology (ASCO) recommend use of the Multina-
tional Association for Supportive Care in Cancer
(MASCC) score to identify patients safe for outpatient
management (Table 1).24 Patients with a MASCC
score of 21 are designated low risk and are recom-
mended for oral antibiotic treatment in an outpatient
setting, so long as they do not meet additional criteria
that dictate inpatient care (see Data Supplements S1
and S2, available as supporting information in the
online version of this paper).
Emergency physicians are challenged by the require-
ment to be aware of recommendations from various
areas of medicine. They (and their collaborating oncol-
ogists, who often give input by phone) may err on the
side of more-aggressive care, resulting in the overuse
of broad-spectrum IV antibiotics and hospital admis-
sion. At our institutions, we have documented a lack
of guideline familiarity, especially among emergency
physicians, with a bias toward inpatient care and par-
enteral antibiotics for all FN cases.5 This patient popu-
lation is particularly vulnerable to adverse medication
reactions, colonization with drug-resistant organisms,
antibiotic complications (e.g., Clostridium difficile coli-
tis) and iatrogenic adverse events associated with an
avoidable hospitalization.2,3
Table 1
MASCC Index
MASCC* risk-index score
Burden of illness (symptom severity)
No or mild symptoms 5 comprehensive cancer center. The Brigham and
Moderate symptoms 3
Severe symptoms or moribund 0 Womens Hospital is an urban, tertiary care teaching
No hypotension (sBP 90 mm Hg) 5 hospital; the ED had 60,050 adult visits in 2014 and
No chronic obstructive pulmonary disease 4
Solid tumor or hematologic malignancy without 4 is the main source of emergency and inpatient care for
previous fungal infection
No dehydration requiring IV therapy 3
Outpatient status at onset of fever 3 We queried an electronic health record database to
Age < 60 y 2
MASCC = Multinational Association for Supportive Care in
Cancer; sBP = systolic blood pressure.
*MASCC Score 21 is considered low risk.
Baugh et al. FEBRILE NEUTROPENIA RISK STRATIFICATION
Our aim was to assess the treatment rendered and
outcomes associated with emergency department (ED)
visits for cancer patients with FN and to compare
guideline concordance among high-risk and low-risk
groups. Investigating the connection between manage-
ment guidelines, actual care delivered, and patient out-
comes is an important first step toward improving the
quality of care.
METHODS
Study Setting and Population
We conducted a structured chart review of cancer
patients with FN presenting to the ED of an urban
tertiary care teaching hospital affiliated with a large
cancer center, between January 2010 and December
2014. A medical student trained to perform the
structured chart review collected all data, similar to
recent investigations into the care of this patient popu-
lation and in accordance with previously published
best practices for chart review investigations.68 The
first author reviewed a random sample of 20 cases
(12% of all) to calculate a kappa coefficient around
MASCC score agreement, which was j = 0.8 (95%
confidence interval [CI] = 0.5 to 1.0). Each case was
preassigned with a unique case number, and we used
a random-number generator to pull 20 cases from the
total pool. We assessed guideline concordance of inpa-
tient/outpatient management and oral/parenteral
antibiotics, stratifying by low versus high risk. In addi-
tion to MASCC score components, we also reviewed
ED notes for the presence of any high-risk IDSA or
ASCO criteria, even if the MASCC score was low
risk. If any high-risk criteria were present, we took a
conservative approach and classified the patient as
high risk.
We assessed clinical outcomes at 30 days via elec-
tronic medical record review. The Dana Farber Cancer
Institute is a National Cancer Institutedesignated
Dana Farber patients.
find all patients with active cancer seen in the ED
with neutropenia during the study period and then
reviewed visit notes to find patients with a diagnosis
of FN without a clear source of infection (e.g., lobar
ACADEMIC EMERGENCY MEDICINE January 2017, Vol. 24, No. 1 www.aemj.org
930
Patients with absolute neutrophil count <1000
within 2 days of ED visit
153 patients excluded with suspected source of infection at index ED visit:
326
Patients with neutropenia at ED visit and
reported or measured fever >100.4F
173
Patients without suspected source of infection
44 129
Low risk High risk
Figure 1. Search strategy and exclusion criteria for study cohort.
consolidation on chest x-ray and clinical symptoms of
pneumonia; see Figure 1 for details) at the conclusion
of the index ED visit. We did not use ICD-9 data for
selection of patients.
We defined neutropenia as an absolute neutrophil
count < 1000 cells/mm3 and fever as any recorded or
reported temperature > 38.0C.2 We defined active
cancer as any cancer with treatment in the previous
6 months (i.e., chemotherapy, radiation therapy, or
surgery).
Study Protocol and Measurements
We categorized patients as low or high risk accord-
ing to the recommendations of IDSA and ASCO.
Low-risk patients were required to have a MASCC
score of 21, but also the absence of another clini-
cal indication for inpatient management as defined
in the ASCO and IDSA guidelines (Data Supple-
ment S1 and S2). High-risk patients had either a
MASCC score of <21 or at least one clinical indica-
tion for inpatient care.
85
604 patients excluded without neutropenia at ED visit or fever
Pulmonary infiltrate with respiratory symptoms
Pyuria with urinary tract infection symptoms
Indwelling central line with suspected line infection
Exam findings suggestive of cellutlitis
Other clear exam findings suggestive of infectious source
The MASCC score was originally created as a tool
to be used prospectively to determine the risk of
adverse outcomes in cancer patients with FN. In our
study, we applied this score retrospectively via chart
review. Some of the components of the score are
objective and simple to abstract from a chart (e.g.,
patient age). However, two components are inherently
subjective: burden of disease and presence of dehydra-
tion requiring IV fluids.
Regarding burden of disease, we assigned none or
mild if the ED note described the patient as well
appearing or in no distress, with the absence of
hypotension (systolic pressure < 90 mm Hg), tachyp-
nea (respiratory rate 24 breaths/min), severe tachy-
cardia (heart rate 120 beats/min), or hypoxia (room
air oxygen saturation < 90%). We categorized the bur-
den of disease as severe or moribund status if the
ED note described the patient as in any degree of dis-
tress or ill appearing or if the patient was noted to
have any of the vital sign abnormalities described
above. We designated the disease burden as
86
moderate in the absence of criteria fitting either of
the two scenarios above.
Regarding dehydration requiring IV fluids, we desig-
nated the patient as dehydrated if the ED note docu-
mented that the patient appeared dehydrated or had
physical examination findings consistent with dehydra-
tion (i.e., dry or tacky mucous membranes, poor skin
turgor) and also received IV hydration. We also
labeled patients as dehydrated if their BUN:creatinine
ratio was > 20:1 and their BUN or creatinine was
above the upper limit of normal range (>23 and >1.2
mg/dL, respectively).
We defined bacteremia or fungemia as a positive
blood culture with 1) at least one blood culture posi-
tive with no indication of suspected contaminants in
the patient notes and 2) a diagnosis of bacteremia/fun-
gemia present in the patients discharge note.911 We
defined sepsis-induced hypotension as systolic pres-
sure < 90 mm Hg during any part of the hospital stay
with suspected source of infection.
Key Outcome Measures
Our main outcome measure was the proportion of
patients with guideline-concordant management. We
designated care as guideline concordant if both dispo-
sition (home vs. inpatient) and route of antibiotics
(oral vs. parenteral) corresponded to guideline recom-
mendations. We report results as risk ratios (RRs),
because we selected participants based on exposure,
not based on outcome, making the RR the appropriate
metric.
Our secondary outcome measures were the
identification of bacteremia or fungemia (i.e., positive
blood cultures not suspected to be a contaminant),
sepsis-induced hypotension, or death within 30 days
of the index ED visit, stratified by risk level. We also
examined the use of vancomycin, which is not recom-
mended by the guidelines as empiric treatment with-
out qualifying risk factors, such as history of prior
methicillin-resistant Staphylococcus aureus infection or
suspected indwelling line infection.12
Data Analysis
For our main outcome, we report the percentage with
binary 95% CI. To evaluate predictors of guideline
discordance, we constructed a multivariable logistic
regression model with guideline concordance as the
outcome and the following predictors, chosen a priori:
low versus high risk (binary), age (continuous), sex (bi-
nary), cancer type (solid or hematologic, dichotomous),
Baugh et al. FEBRILE NEUTROPENIA RISK STRATIFICATION
and stem cell or bone marrow transplant (binary).
These predictors were chosen based on biologic plausi-
bility and clinical relevance. All of these predictors
chosen a priori were included in the final model. We
included interaction terms for each predictors interac-
tion with risk level, and upon finding that none was
statistically significant, we reverted to the basic model
with no interaction terms. All variance inflation factors
for the included predictors were < 3, implying lack of
problematic collinearity. We performed all statistical
analyses with StataMP 13. The study was approved by
our institutional review board.
Sensitivity Analysis
We performed a sensitivity analysis of our results by
varying the subjective elements of the MASCC score
most vulnerable to disparate valuation: the assessment
of disease burden and dehydration requiring IV antibi-
otics. We tested whether adding/subtracting points in
these components of the score would potentially move
patients from low risk to high risk or vice versa.
First, we tested the impact of misclassifying the dis-
ease burden, which is a subjective determination of
patient acuity at the time of presentation. In cases
where we had determined no or mild symptoms, we
upgraded the score to moderate; in cases determined
as moderate, we upgraded the score to severe or
moribund. Second, we tested the possibility of dehy-
dration misclassification. We applied more inclusive
criteria of either BUN:creatinine ratio of >20:1 or
abnormal BUN or creatinine values above the normal
cutoff ranges to classify patients as dehydrated. Previ-
ously, we required both to satisfy our definition. All
other physical examination findings and indication of
dehydration in the charts still applied to this reclassifi-
cation.
RESULTS
Characteristics of Study Subjects
Figure 1 is a participant flow chart. We identified 930
cases of neutropenia that coincided with an ED visit,
of which 326 had fever, identified by manual chart
review. After excluding FN cases with a known etiol-
ogy corroborated by physical examination or laboratory
findings (Figure 1), and patients without active cancer,
we obtained a final sample of 173 ED visits by
patients with undifferentiated FN. We classified 44
(25%) as low risk and 129 (75%) as high risk. We
ACADEMIC EMERGENCY MEDICINE January 2017, Vol. 24, No. 1 www.aemj.org 87

present participant characteristics in Table 2. The
mean absolute neutrophil count was 500 in low-risk
patients and 410 in high-risk patients (difference = 80;
95% CI = 20 to 200).
Main Results
Figure 2 displays a breakdown of guideline discor-
dance by disposition and by route of antibiotic admin-
istration. Overall, 52 patients (30%, 95% CI = 23%
to 37%) received guideline-discordant care, including
43 (98%, 95% CI = 88% to 100%) of low-risk
patients and 9 (7%, 95% CI = 3.2% to 13%) of high-
risk patients. For the low-risk group, discordance was
driven by guideline-discordant inpatient admission in
nearly all discordant cases, the majority of whom also
received IV antibiotics in discordance with guidelines
(Figure 2). The median hospital length of stay in this
group was 4 days (interquartile range = 2-6 days). For
high-risk patients, discordance was very low and simi-
lar across both antibiotic route and setting of care,
with nearly all admitted for inpatient care and treated
with parenteral antibiotics. Oral or no antibiotic treat-
ment represented the majority of discordant care in
the high-risk group.
The crude RR for guideline-discordant care by risk
category was 14, with more discordance in the low-risk
group. Table 3 displays the results of the multivariable
analysis and shows that being in the low-risk category
was a strong predictor of guideline discordant care
(RR = 14.5). Hematologic malignancy was the only

Table 2
Characteristics of 173 Patients with FN Presenting to the ED

Characteristic Low risk High risk % Difference (95% CI)

All cases (N = 173) 44 (25%) 129 (75%)
Age (y), median (interquartile range) 58 (4766) 61 (4967) 1 ( 6 to 3)
Sex
Female (n = 99) 26 (59%) 73 (57%) 2.5 ( 15 to 20)
Male (n = 74) 18 (41%) 56 (43%) 2.5 ( 1.9 to 1.5)
Underlying malignancy
Solid (n = 92) 19 (43%) 73 (57%) 13 ( 31 to 3.8)
Hematologic (n = 81) 25 (57%) 56 (43%) 13 ( 3.8 to 31)
Stem cell or bone marrow transplant (n = 21) 5 (11%) 16 (12%) 1.0 ( 12 to 10)

FN = febrile neutropenia.

RR 14 (95% CI 7.5-26) RR 39 (95% CI 13-120) RR 16 (95%CI 8.0-31)

98% 98%
100% 91%

80%

60%

40% 30% 30%

25%
20% 7% 6%
2%
0%
All Cases Low Risk High Risk All Cases Low Risk High Risk All Cases Low Risk High Risk

Either setting of care or Inappropriate setting of care Inappropriate antibiotic route

antibiotic route
(Inpatient for low-risk; (Parenteral for low-risk; oral for
outpatient for high-risk) high-risk; no antibiotics at all for
either group)
Figure 2. Discordant care between recommended and actual management of ED patients with FN. FN = febrile neutropenia; RR = risk
ratio.
88 Baugh et al. FEBRILE NEUTROPENIA RISK STRATIFICATION

Table 3 when both disease burden and dehydration criterion

Multivariable Analysis of Predictors of Guideline Discordance
RR in Predicting
Predictor Guideline Discordance
Low risk (vs. high risk) 14.5
Age (decade) 1.0 (not signicant)
Male sex (vs. female) 0.8 (not signicant)
Hematologic malignancy 0.8 (signicant)
(vs. solid)
Stem cell or bone 0.9 (not signicant)
marrow transplant (vs. not)
RR = risk ratio.
other variable that significantly predicted discordant
treatment, although significance was borderline.
In the high-risk group, 18 patients (32%, 95%
CI = 20% to 45%) received vancomycin without a
clinical indication. Among all patients who received
IV antibiotics (n = 153), vancomycin was used with-
out guideline support in 26 cases, or 17% (95% CI =
11% to 23%).
We display 30-day clinical outcomes in Figure 3.
No patients were lost to follow-up at 30 days. Compar-
ing low-risk with high-risk patients, positive blood cul-
ture rates were significantly higher in the high-risk
group and no low-risk patients experienced sepsis-
induced hypotension or death, compared with 12
(9.3%) and 7 (5.4%) of high-risk patients, respectively.
Positive blood cultures were predominantly due to bac-
teremia, with fungemia present in only one high-risk
patient and one low-risk patient.
Our sensitivity analysis yielded only an additional
three cases crossing the threshold from low risk to
high risk when upgrading the disease burden. The
more-inclusive dehydration criterion resulted in seven
low-risk patients being reclassified as high risk. A total
of 12 low-risk patients were reclassified as high risk
changed at the same time. With all reclassifications
applied, management was guideline discordant in 31
95%CI (96.9%, 95% CI = 83.8% to 99.9%) low-risk patients
7.826.8 versus 12 (8.5%, 95% CI = 4.5% to 14%) high-risk
0.991.01 patients (RR = 11, 95% CI = 6.6 to 20). Comparing
0.71.0
0.70.99 low-risk versus high-risk patients, within 30 days, one
(3.1%) versus seven (5.0%) had bacteremia or funge-
0.61.3
mia (RR = 1.6, 95% CI = 0.2 to 13), 0 versus 12
(8.5%) had sepsis-induced hypotension (difference =
8.5, 95% CI = 3.9 to 13), and 0 versus 7 (5.0%) died
(difference = 5.0, 95% CI = 1.4 to 8.5).
DISCUSSION
Our investigation suggests that emergency physicians
are indiscriminately using IV antibiotics and hospital-
ization in cancer patients with low-risk FN. Low-risk
patients comprised 25% of all FN cases, and manage-
ment was more aggressive than guidelines recommend
in 98% of these patients with a median hospital
length of stay of 4 days. At the same time, there were
no episodes of sepsis-induced hypotension or death
within 30 days in the low-risk group. This supports
the guidelines ability to identify patients who are
appropriate candidates for outpatient care and oral
antibiotics.13 First-line therapy for low-risk patients is
oral fluoroquinolones, which have excellent bioavail-
ability.14 Low risk is not synonymous with no risk
the 2.2% rate of bacteremia or fungemia in this group
highlights the importance of close outpatient follow-
up, both with rapid access to providers and with a reli-
able patient capable of seeking care if his or her clini-
cal condition worsens. It is important to understand
that fluoroquinolones have the same bioavailability by
mouth as by the IV route, and thus the rare patient

RR 2.4 (95% CI 0.3 - 21) Diff=9.3 (95% CI 4.3-14) Diff=5.4 (95%CI 1.5-9.3)

10.0% 9.3%

8.0%

6.0% 5.4% 5.4%

4.0%
2.2%
2.0%
0.0% 0.0%
0.0%
Positive blood culture Sepsis-induced hypotension Death

Low Risk High Risk

Figure 3. Thirty-day clinical outcomes in ED patients with FN. FN = febrile neutropenia; RR = risk ratio.
ACADEMIC EMERGENCY MEDICINE January 2017, Vol. 24, No. 1 www.aemj.org
with nonseptic bacteremia would be treated as well at
home as in the hospital.15
Our results show that guideline discordance was
primarily driven by overtreatment of low-risk patients,
not undertreatment of high-risk patients. As expected,
setting of care and use of parenteral versus oral antibi-
otics were likely to be closely linked to one another in
the management plan. We were surprised to find that
increased age did not predict risk of guideline discor-
dance in the controlled multivariable analysis. We had
expected to observe a tendency to hospitalize patients
at higher age despite a low-risk determination.16,17
Seventeen percent of patients who received IV
antibiotics were treated with vancomycin without
guideline support, increasing the unnecessary risk of
vancomycin-resistant enterococcus bacteremia in a vul-
nerable patient population.12,18 This finding reveals
an opportunity to improve the quality of care via edu-
cation and implementation of tools (i.e., electronic
health record decision support) to support antibiotic
stewardship in a vulnerable population.2,3,12,18,19 The
target of such efforts should include both emergency
physicians and oncologists, since it is unlikely that
treatment and disposition decisions for these patients
are made without input from oncologists. A recent
survey found that guideline awareness and use was sig-
nificantly higher for oncologists, yet still not optimal.5
The MASCC score has been established for over a
decade, but it is neither highly sensitive nor specific
for adverse patient outcomes.20 MASSC also does not
meet optimal characteristics of clinical decision rules.21
A recent alternative scoring method, the CISNE (Clin-
ical Index for Stable Febrile Neutropenia) score is pur-
portedly more accurate in predicting adverse
outcomes; we did not, however, include this score in
our analysis due to its lack of penetration in existing
society recommendations and difficulty in acquiring its
scoring factors from retrospective chart reviews.22
While we found no cases of sepsis-induced hypoten-
sion or death in the low-risk population, 2.2% of
these patients did have positive blood cultures. We
recommend following IDSA and ASCO guidelines,
which advise sending these patients home.2,3 However,
if discharge to home after initial ED evaluation is not
the best plan (i.e., barriers to close outpatient follow-
up due to weekend/holiday), care in an observation
unit may be an acceptable alternative to an inpatient
admission. The duration of a typical observation stay
will not span the necessary time for a final blood cul-
ture result, and the patient is still exposed to the
89
hazards of hospitalization, but it may be a superior
alternative to inpatient admission since that exposure
is limited to around 15 hours for an observation unit
stay, less than half the duration of a typical inpatient
admission.23 Hospitalization carries risk of nosocomial
infections, and treatment with broad-spectrum antibi-
otic confers increased risk of C. difficile colitis and
selection for multidrug-resistant bacterial strains.
LIMITATIONS
Our study has several limitations. First, it was a single-
center study, which limits generalizability. However,
this initial work is an important first step toward rec-
ognizing gaps in care in the treatment of oncologic
emergencies. We are members of the CONCERN, a
newly formed research consortium sponsored by the
National Cancer Institute and are planning a large
multicenter study that may confirm the results of this
single-center study.1,24 Second, we determined the
MASCC score via retrospective chart review; as such,
we are limited by the study design to ascertain whether
any sepsis-induced hypotension or death was pre-
vented by more aggressive inpatient management of
low-risk patients. A prospective cohort study, therefore,
may be indicated to further evaluate the efficacy of
existing society FN management guidelines. However,
our sensitivity analysis tested the most subjective com-
ponents of the risk stratification criteria, and our study
outcomes were not significantly changed. Third, our
regression model may lack important unmeasured
covariates and should be validated before reaching
definitive conclusions about its merit. Fourth, nonad-
herence to treatment guidelines could be a function
either of an awareness gap or of patient factors not
captured in the chart review. Additionally, we could
not reliably ascertain if the management plan was dri-
ven by the emergency physician or outpatient oncolo-
gist. Fifth, we did not power this study to detect
differences in clinical outcomes between risk groups.
CONCLUSIONS
Treatment of low-risk cancer patients with febrile
neutropenia often did not follow national specialty
society guidelines. Low-risk patients had a low rate
of adverse outcomes but were hospitalized and trea-
ted with parenteral antibiotics frequently. Further
research is needed to see if this gap between treat-
ment recommendations and patterns of care is more
90
widespread and, if so, investigate strategies to better
align them.
References
1. Greene J. CONCERN for cancer. New National Institutes
of Health Network to Focus on Cancer Patients in the
Emergency Department. Ann Emerg Med 2015;66:A13
A15.
2. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical prac-
tice guideline for the use of antimicrobial agents in neu-
tropenic patients with cancer: 2010 update by the
Infectious Diseases Society of America. Clin Infect Dis
2011;52:e5693.
3. Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial
prophylaxis and outpatient management of fever and
neutropenia in adults treated for malignancy: American
Society of Clinical Oncology clinical practice guideline. J
Clin Oncol 2013;31:794810.
4. Klastersky J, Paesmans M, Rubenstein EB, et al. The
Multinational Association for Supportive Care in Cancer
risk index: a multinational scoring system for identifying
low-risk febrile neutropenic cancer patients. J Clin Oncol
2000;18:303851.
5. Baugh CW, Brooks GA, Reust AC, et al. Provider famil-
iarity with specialty society recommendations for risk strati-
fication and management of patients with febrile
neutropenia. New England Regional SAEM Meeting,
Worcester, MA, 2016.
6. Owolabi DK, Rowland R, King L, et al. A comparison of
ED and direct admission care of cancer patients with feb-
rile neutropenia. Am J Emerg Med 2015;33:9669.
7. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC,
Steiner J. Chart reviews in emergency medicine research:
where are the methods? Ann Emerg Med 1996;
27:3058.
8. Kaji AH, Schriger D, Green S. Looking through the retro-
spectoscope: reducing bias in emergency medicine chart
review studies. Ann Emerg Med 2014;64:2928.
9. Hall KK, Lyman JA. Updated review of blood culture con-
tamination. Clin Microbiol Rev 2006;19:788802.
10. Weinstein MP. Blood culture contamination: persisting
problems and partial progress. J Clin Microbiol
2003;41:22758.
11. Mirrett S, Weinstein MP, Reimer LG, Wilson ML, Reller
LB. Relevance of the number of positive bottles in deter-
mining clinical significance of coagulase-negative staphylo-
cocci in blood cultures. J Clin Microbiol 2001;39:327981.
12. Libuit J, Whitman A, Wolfe R, Washington CS. Empiric
vancomycin use in febrile neutropenic oncology patients.
Open Forum Infect Dis 2014;1:ofu006.
13. Klastersky J, Paesmans M, Georgala A, et al. Outpatient
oral antibiotics for febrile neutropenic cancer patients
Baugh et al. FEBRILE NEUTROPENIA RISK STRATIFICATION
using a score predictive for complications. J Clin Oncol
2006;24:412934.
14. Sharma PC, Jain A, Jain S. Fluoroquinolone antibacteri-
als: a review on chemistry, microbiology and therapeutic
prospects. Acta Pol Pharm 2009;66:587604.
15. Belforti RK, Lagu T, Haessler S, et al. Association
between initial route of fluoroquinolone administration
and outcomes in patients hospitalized for community-
acquired pneumonia, Clin Infect Dis 2016; 63:19.
16. LaMantia MA, Platts-Mills TF, Biese K, et al. Predicting hos-
pital admission and returns to the emergency department
for elderly patients. Acad Emerg Med 2010;17:2529.
17. Wallace E, Stuart E, Vaughan N, Bennett K, Fahey T,
Smith SM. Risk prediction models to predict emergency
hospital admission in community-dwelling adults: a sys-
tematic review. Med Care 2014;52:75165.
18. DiazGranados CA, Jernigan JA. Impact of vancomycin
resistance on mortality among patients with neutropenia
and enterococcal bloodstream infection. J Infect Dis
2005;191:58895.
19. Davey P, Brown E, Charani E, et al. Interventions to
improve antibiotic prescribing practices for hospital
inpatients. Cochrane Database Syst Rev 2013; 4:
CD003543.
20. Bitar RA. Utility of the Multinational Association for Sup-
portive Care in Cancer (MASCC) Risk Index Score as a
Criterion for Nonadmission in Febrile Neutropenic
Patients with Solid Tumors. Perm J 2015;19:3747.
21. Green SM, Schriger DL, Yealy DM. Methodologic stan-
dards for interpreting clinical decision rules in emergency
medicine: 2014 update. Ann Emerg Med 2014;64:28691.
22. Carmona-Bayonas A, Jimenez-Fonseca P, Virizuela Ech-
aburu J, et al. Prediction of serious complications in
patients with seemingly stable febrile neutropenia: valida-
tion of the Clinical Index of Stable Febrile Neutropenia
in a prospective cohort of patients from the FINITE
study. J Clin Oncol 2015;33:46571.
23. Mace SE, Graff L, Mikhail M, Ross M. A national survey
of observation units in the United States. Am J Emerg
Med 2003;21:52933.
24. Brown J, Grudzen C, Kyriacou DN, et al. The emergency
care of patients with cancer: setting the research agenda.
Ann Emerg Med 2016 [Epub ahead of print].
Supporting Information
The following supporting information is available in
the online version of this paper:
Data Supplement S1. Infectious Diseases Society
of America Clinical Practice Guideline: Additional
Specific Clinical Criteria that Exclude Oncology
Patients with FN from Initial Outpatient Care even
with a MASCC Score 21.
ACADEMIC EMERGENCY MEDICINE January 2017, Vol. 24, No. 1 www.aemj.org 91

Data Supplement S2. American Society of Clinical Patients with FN from Initial Outpatient Care even
Oncology Clinical Practice Guideline: Additional with a MASCC Score 21.
Specific Clinical Criteria* that Exclude Oncology