Identificación de barreras de infraestructura y educación para el inicio temprano de los antibióticos en pacientes con neutropenia febril.

1. Pediatr Blood Cancer 2012;59:431–435
Identification of Educational and Infrastructural Barriers to Prompt Antibiotic
Delivery in Febrile Neutropenia: A Quality Improvement Initiative
Erica Burry, Bsc,1
Angela Punnett, MD,2
Ashley Mehta, Bsc, CCRP,2
Jennifer Thull-Freedman, MD, Msc,3
Lisa Robinson, BscN, RN,3
and Sumit Gupta, MD
2
*
INTRODUCTION
Febrile neutropenia (FN) is a common treatment complication
in pediatric oncology patients, with a low but identifiable mortali-
ty rate [1]. Prompt administration of broad-spectrum antibiotics
has been considered standard of care for FN for decades [2].
However, most guidelines do not define prompt administration.
The most recent guidelines published by the Infectious Diseases
Society of America briefly cite administration within 2 hours of
presentation as ideal, but do not discuss this in detail [3].
While evidence is lacking to support a particular target, some
institutions have implemented a target as low as 30–60 minutes
from arrival [4,5].
Though the literature has not definitively correlated a delay
in antibiotics to adverse outcomes in children with FN, such
an association has been shown in other clinical situations [6].
Battleman et al. [6] showed a correlation between the timing of
antibiotic administration and the length of stay in hospital in
adults with community-acquired pneumonia, suggesting that an-
tibiotic delay may lead to increased morbidity and financial ex-
penditure. Rivers et al. [7] showed better outcomes and improved
survival with early goal-directed therapy for adults with severe
sepsis and septic shock. The Surviving Sepsis Campaign advo-
cates for antibiotic initiation within an hour for sepsis requiring
intensive care [8,9]. Although these studies were not conducted in
oncology patients, each advocates for early treatment of infectious
disease. In the absence of an accepted standard for time to antibi-
otic administration in the setting of FN, a target of 60 minutes
may be ambitious but is not unreasonable and not without
precedent.
Very few studies have examined the prevalence and predictors
of antibiotic delay in pediatric FN. Such information is necessary
to design appropriate interventions. Our primary objectives were
therefore to describe the median time to antibiotic administration
at our institution and to identify barriers to prompt administration.
Our secondary objective was to determine predictors of delayed
antibiotic administration.
METHODS
A mixed methodology approach was used to investigate the
delays in and barriers to antibiotic administration in pediatric
oncology patients with FN in the emergency department (ED).
A chart review of oncology patients presenting to the ED was
conducted to determine the prevalence and predictors of antibiotic
delay. Concurrently, focus groups including representatives from
all disciplines involved in FN management were completed using
lean methodology to identify barriers to prompt treatment.
As per institutional guidelines, quality improvement projects
are reviewed and approved by the institution’s Quality and Risk
Management Department, ensuring compliance with institutional
policies and ethical guidelines for projects defined as quality
improvement. As the collection of patient data was limited to
retrospective chart review, informed consent was not required.
Chart Review
A chart review was completed using a random sample of 50
episodes of FN in the ED over a 1-year period. Inclusion criteria
included any patient with a known diagnosis of malignancy aged
0–18 years who presented to the ED with a complaint of fever and
who subsequently was found to meet the local definition for FN.
Background. Antibiotic administration within 60 minutes of pre-
sentation for medical care may be used as a treatment target for
febrile neutropenia (FN); however, anecdotal evidence suggests this
target is often missed. Few studies have examined the prevalence or
causes of delay. We describe the median time to antibiotic admin-
istration at our institution, predictors of delay, and barriers to
prompt administration to inform quality improvement strategies.
Procedure. A random sample of 50 episodes of FN presenting to
the emergency department (ED) between 2008 and 2009 were
reviewed. Times between triage, MD assessment, lab results, and
antibiotic administration were recorded. Patient and ED variables
were examined as possible predictors of delay. In parallel, lean
methodology was used to identify system inefficiencies. A trained
moderator conducted group interviews with interdisciplinary repre-
sentatives involved in the emergency care of neutropenic patients to
identify process barriers to prompt antibiotics. Results. The median
time from triage to antibiotics was 216 minutes (interquartile
range [IQR] ¼ 151–274 minutes). The greatest delay occurred fol-
lowing the reporting of lab results (152 minutes, IQR ¼ 84–
210 minutes). Only fall season predicted a longer time to antibiotics
(P ¼ 0.03). The lean process identified unnecessary areas of delay
between departments. Conclusions. Time to antibiotic administra-
tion exceeded 1 hour. The chart review and lean process suggested
targets for educational and infrastructural interventions, including
an ED pre-printed order sheet, targeted combined subspecialty ed-
ucation between emergency and hematology/oncology staff, and
family education. A mixed methodology approach represents a
model for improving process efficiency and meeting ‘‘best-practice’’
targets in medicine. Pediatr Blood Cancer 2012;59:431–435.
ß 2011 Wiley Periodicals, Inc.
Key words: anti-bacterial agents; cancer; fever; neutropenia; pediatrics; quality improvement
1
Faculty of Medicine, University of Toronto, Toronto, Canada;
2
Division of Haematology/Oncology, The Hospital for Sick Children,
Toronto, Canada; 3
Division of Emergency Medicine, The Hospital for
Sick Children, Toronto, Canada
Grant sponsor: C17 Council.
Conflict of interest: Nothing to declare.
Erica Burry and Angela Punnett contributed equally to this work.
*Correspondence to: Sumit Gupta, MD, Division of Haematology/
Oncology, The Hospital for Sick Children, 555 University Avenue,
Toronto, ON, Canada M5G 1X8. E-mail: sumit.gupta@sickkids.ca
Received 25 July 2011; Accepted 12 October 2011
ß 2011 Wiley Periodicals, Inc.
DOI 10.1002/pbc.23418
Published online 6 December 2011 in Wiley Online Library
(wileyonlinelibrary.com).

2. An ED electronic patient tracking system was used to identify
all such patients who presented between December 1, 2008 and
November 30, 2009. Fever was defined as an oral temperature of
!388C or an axillary temperature of !37.58C. Neutropenia was
defined as an absolute neutrophil count (ANC) 0.5 Â 109
/L.
Patients appearing toxic receive antibiotics regardless of ANC,
and were therefore also included. According to local protocol, all
patients meeting FN criteria receive broad-spectrum antibiotics
and are admitted.
Eligible patients were stratified by season by date of presenta-
tion: December 1 to February 28 (winter), March 1 to May 31
(spring), June 1 to August 31 (summer), and September 1 to
November 30 (fall). Thirteen charts were randomly selected
from each of the winter and fall groups, while 12 charts were
randomly selected from each of the spring and summer groups,
for a total of 50 charts. Only one episode per patient was used in a
given season.
The time of triage, initial medical assessment, entry of blood-
work orders, receipt of bloodwork, reporting of lab results, entry
of antibiotic orders and first antibiotic administration were
recorded for each episode. Possible predictors of delayed admin-
istration were also recorded, including both patient-level (gender,
age, and diagnosis), and episode-level (season, time of presenta-
tion, febrile at presentation, training level of first assessing physi-
cian, and use of ED-stocked antibiotics) variables. The definition
for season can be found above. Time of presentation was sub-
divided into day, evening, and night, with day defined as 8:00 to
17:00, evening as 17:00 to 23:00, and night as 23:00 to 8:00. The
training level of first assessing physician was subdivided into
junior versus senior, with junior defined as a medical student,
first or second year pediatrics resident and senior defined as a
third or fourth year pediatrics resident, fellow or attending
physician.
Median times between events were calculated. The episodes
were then categorized into below median or above median time to
antibiotic administration, using the median time from triage to
antibiotic administration (216 minutes) as the cut off between
groups. The median time was used as the cut off for the purposes
of statistical analysis rather than the 60-minute benchmark de-
scribed in the introduction, as none of the 50 episodes reviewed in
this study received antibiotics within 60 minutes. Logistic regres-
sion was used to examine predictors of delayed antibiotic admin-
istration. Statistical analyses were performed using SAS-PC
software (version 9.2; SAS Institute, Cary, NC). Statistical signif-
icance was defined as P < 0.05.
Lean Methodology
Independently, lean methodology was used to conduct group
interviews made up of representatives from all disciplines in-
volved in the care of oncology patients with FN. Lean principles
were first applied in the automotive industry to streamline
manufacturing processes, and have since been adapted for use
in health care to identify system inefficiencies. The main goal
of lean methodology is to distinguish value-added and non-val-
ued-added tasks in order to identify and eliminate waste [10–12].
This allows front-line workers to improve flow and better serve
customers’ needs by ensuring that every step adds value to the
process. In health care, waste is described as an action that is not
required for patient care, decreasing quality of care and increasing
wait times [10–12]. Lean methodology focuses on bringing front-
line staff together to identify areas of waste using value stream
mapping [12,13]. Group participants outline step-by-step the
events that occur in the care of a patient. These events are the
actual steps taken on a daily basis, and not what ideally should
occur. Once this has been completed, members then identify
actions that do not add value to the patient’s care. Interventions
are put into place to eliminate the identified waste to streamline
patient care, improve patient experience and decrease wait times
[12,13]. The lean process has the very specific purpose of stream-
lining a process without additional resources, and aims at produc-
ing tangible and feasible results [12].
In this study, a moderator trained in lean techniques (A.M.)
conducted interviews with a group consisting of ED and oncology
nurses, ED and oncology staff and trainee physicians, laboratory
personnel, and pharmacy personnel. The group first developed a
flow diagram outlining the events that occur in the treatment of
FN from triage to antibiotic administration. Consensus was then
sought on barriers to prompt treatment. Finally, possible interven-
tions to improve delays caused by these barriers were discussed.
The results of the chart review were discussed throughout the lean
process.
RESULTS
One hundred seventy-nine episodes of FN among known on-
cology patients presented to the ED during the study period. Fifty-
three presented in winter, 39 in spring, 42 in summer, and 54 in
fall. Demographic and episode-level information for the 50 charts
selected for review are seen in Table I. The median time between
triage and antibiotic administration was 216 minutes (interquartile
TABLE I. Characteristics of Study Cohort
Characteristic Cohort (n ¼ 50)
Gender, N (%)
Male 27 (54)
Female 23 (46)
Age (years), median (IQR) 5 (3, 12)
Diagnosis, N (%)
Leukemia/lymphoma 31 (62)
Other 19 (38)
Season, N (%)
Summer 12 (24)
Fall 13 (26)
Winter 13 (26)
Spring 12 (24)
Time of day, N (%)
Day 20 (40)
Evening 20 (40)
Night 10 (20)
Febrile at presentation, N (%)
Yes 31 (62)
No 19 (38)
Training of first assessing MD, N (%)
Senior 30 (60)
Junior 17 (34)
Ward stock antibiotics, N (%)
Yes 46 (92)
No 4 (8)
IQR, interquartile range; MD, medical doctor; N, number.
432 Burry et al.
Pediatr Blood Cancer DOI 10.1002/pbc

3. range [IQR] 151–274 minutes). The longest delays occurred be-
tween the lab report of neutropenia and antibiotic administration,
with a median time of 152 minutes (IQR 84–210 minutes). Other
end points, such as timing of medical assessment, bloodwork
orders, and antibiotic orders were also investigated, but were
not reliably noted in patient charts. It was felt that time periods
that included these end points could not be measured with
confidence.
The results of univariate analyses of predictors of delayed
antibiotic administration are presented in Table II. Presentation
to the ED during the fall season was significantly associated
with delayed antibiotic administration (odds ratio [OR] 10, 95%
confidence interval [CI] 1.6–63, P ¼ 0.03). No other variable
examined significantly predicted delay. When a sensitivity analy-
sis was run excluding the fall season, the median time to anti-
biotics was 199 minutes (IQR 142–257 minutes); no variable
examined significantly predicted delay.
The focus group consisted of eight individuals representing the
groups noted above. The interviews first resulted in the develop-
ment of a flow diagram outlining each event that occurred in FN
management from triage to antibiotics, illustrated in Figure 1.
This diagram outlined the actual steps that occurred, despite
any problems that may have been associated with an individual
step or the order of steps.
During the process of developing the flow diagram, a number
of assumptions and misunderstandings were uncovered. ED per-
sonnel incorrectly assumed that bloodwork sent to the lab from
the ED was automatically considered to be STAT and, in some
cases, were not labeling them as such. Lab personnel were
therefore not processing these samples immediately. In addition,
ED personnel were unaware that different sizes of specimen vials
had different processing times. Although larger tubes allowed for
faster processing times, smaller tubes were frequently used to
minimize the amount of blood drawn. Though inpatient wards
used a computerized system to print orders on colored paper for
easy identification of urgent requests, written antibiotic orders
from the ED were sent to the pharmacy as paper orders. Conse-
quently, pharmacy personnel were not able to easily identify the
urgency of these orders.
Additionally, ED nursing personnel identified that on parental
request, bloodwork was often delayed until after topical anesthetic
had been applied and taken effect. Very few families had applied
their own topical anesthetic prior to arrival.
Finally, differences in opinion on the most appropriate timing
to access the implanted central venous catheter (port) were un-
covered. Hospital protocol dictated that both peripheral and cen-
tral blood cultures be drawn. However, due to patient comfort,
time management, and often parental request, ED nurses preferred
to wait for peripheral bloodwork results before accessing the port.
ED personnel reported that patients who were not neutropenic
could have their port accessed for cultures and then the access
needle could be immediately removed, thus decreasing patient
and parent anxiety and avoiding the discomfort associated with
dressing removal.
Based on these results, a number of interventions were devel-
oped to overcome the identified barriers. These interventions are
indicated in boxes labeled interventions in Figure 1. The first
intervention was the development of a pre-printed order sheet
for oncology patients with fever. This will standardize the process
of collecting peripheral and central bloodwork and blood cultures
of any oncology patient presenting with a fever. The pre-printed
order sheet will also have a section with the recommended anti-
biotics and dosing to facilitate ordering.
Other interventions focused on bloodwork and antibiotic or-
dering. All bloodwork from patients with suspected FN will be
labeled as STAT. As well, larger tubes will be encouraged. Non-
ward stock antibiotic orders will continue to be sent as paper
orders, but marked to indicate STAT to pharmacy personnel.
Finally, targeted nursing education will occur. One area of focus
will be that of central access; ports will be accessed with periph-
eral bloodwork and before lab results are reported. This will now
be mandated by the pre-printed order sheet. Parents will also be
instructed to use their own supply of topical anesthetic before
arrival.
DISCUSSION
We demonstrated that the median time from arrival to antibi-
otic administration in our institution was close to 3.5 hours. In-
terestingly, in many cases, a large portion of this wait occurred
after the lab report of neutropenia. As all neutropenic patients
receive antibiotics and are admitted in our institution, a median
time of 2.5 hours was spent waiting for treatment after it was
determined to be indicated.
Only season predicted differences in treatment times, with the
longest times occurring during the fall. However, the study period
coincided with the H1N1 outbreak in the fall of 2009. While
treatment times during this period may not be representative of
those of an average fall season, excluding children who presented
TABLE II. Univariate Analysis of Predictors of Delayed
Antibiotics
Characteristics OR 95% CI P-value
Gender
Male — — —
Female 1.2 (0.39, 3.6) 0.72
Age (per year) 0.94 (0.84, 1.1) 0.27
Diagnosis
Leukemia/lymphoma — — —
Other 0.42 (0.13, 1.4) 0.15
Season
Summer — — —
Fall 10 (1.6, 63) 0.03
Winter 3.0 (0.53, 17) 0.98
Spring 2.6 (0.47, 14) 0.78
Time of day
Day — — —
Evening 0.82 (0.24, 2.8) 0.86
Night 0.55 (0.12, 2.5) 0.48
Febrile at presentation
Yes — — —
No 1.2 (0.38, 3.7) 0.77
Training of first assessing MD
Senior — — —
Junior 1.3 (0.39, 4.2) 0.68
Ward stock antibiotics
Yes — — —
No 1.0 (0.13, 7.7) 1.00
CI, confidence interval; MD, medical doctor; OR, odds ratio.
Barriers to Prompt Antibiotic Delivery in FN 433
Pediatr Blood Cancer DOI 10.1002/pbc

4. during the fall did not have a major impact on the analysis. It is
relevant to note that periods of increased ED volume may be
associated with longer treatment delays. It has been previously
shown in the literature that influenza season is associated with
increased length of stay in the ED, increased admissions, and
increased numbers of patients leaving without being seen [14].
Although FN treatment delay has received little attention in
the literature, some investigators have found similar delays and
have developed effective means to improve treatment times. One
study conducted among adult oncology patients found a median
time of 210 minutes between presentation and antibiotic admin-
istration; interestingly, patients with more co-morbidities had
Fig. 1. Lean flow diagram of febrile neutropenia treatment process and proposed interventions.
434 Burry et al.
Pediatr Blood Cancer DOI 10.1002/pbc

5. longer delays [4]. In the pediatric setting, Corey and Snyder [5]
found that average waiting times for antibiotics ranged from 80 to
120 minutes; no one met their aggressive target of 30 minutes.
Through various multi-disciplinary educational initiatives, they
were able to decrease average wait times to 25 minutes, with
80–100% of patients meeting the 30-minute target. While children
in this study were known to be neutropenic prior to arrival and
were evaluated and treated on the pediatric ward instead of the
ED, limiting generalizability to our institution, the positive results
nonetheless support the use of infrastructural and educational
interventions.
During focus group interviews, it became apparent that the
flow of events was not optimal and that identified misunderstand-
ings and assumptions were impeding prompt care. As a result, the
potential interventions noted above were developed through con-
sensus from these interviews. For example, the previous practice
of accessing ports only after bloodwork results were available was
instituted by ED personnel in order to prevent unnecessary taping
and patient discomfort, in keeping with ED and institutional
philosophies of family-centered care to minimize and manage
painful procedures. Education of ED and oncology staff and of
parents on early application or home application of topical anes-
thetic will allow for port access prior to obtaining bloodwork
results without compromising patient comfort. This situation rep-
resents the kind of issue that can only be identified by combining
analysis of quantitative data with the qualitative input of front-line
workers.
At a time of cost-consciousness in healthcare, improving care
through strategies requiring increased resources is not always
feasible. Lean methodology provides an alternative solution by
focusing on improving process efficiency and minimizing waste
[10–13]. The interventions that have been developed in this study
focus on changing the order and flow of events that occur in FN
treatment. Implementing these interventions should result in a
decrease in treatment times without increased resources.
This study has a number of implications for the future. The ED
electronic patient tracking system used to identify cases of FN in
this study will continue to be used to prospectively monitor anti-
biotic administration times. This information will also be used in
future studies to assess the effectiveness of the proposed inter-
ventions, and to identify future targets. Future value stream map-
ping to continuously improve the care provided to FN patients is
planned. Indeed, repeated PDSA (Plan-Do-Study-Act) cycles with
ongoing monitoring of treatment times allow for continuous im-
provement [11].
Several limitations deserve mention. With a sample of only
50 episodes of FN, our power to meet our secondary objective of
determining predictors of delay was limited. However, this was
primarily a quality improvement study designed to determine
treatment times and describe the lean process used to identify
barriers and potential interventions. Future studies with improved
power to evaluate predictors of delays are warranted. The chart
review component of this study was a retrospective analysis, and
was therefore limited to the data present in the electronic medical
record. Time periods that were recorded by hand rather than
computer, such as the time of medical assessment and time of
bloodwork and antibiotics orders, were not regularly available.
We were not able to evaluate time periods between each step in
FN patient care as initially intended due to gaps in data. Thus, we
could not determine how much of the delay after the reporting of
neutropenia was due to delays in physician ordering. There was,
however, complete data on time of antibiotic administration,
allowing us to fulfill our primary objective of determining median
treatment times. Finally, the group interviewed during the lean
focus group consisted of a small number of individuals. However,
while initial input was solicited from these individuals alone, the
proposed interventions were taken back to and approved by the
groups they represented.
In conclusion, the median treatment time for FN in pediatric
oncology patients at our institution was 216 minutes, which is
likely to be longer than ideal even in the absence of evidence for a
standard target. Lean methodology identified areas of waste in
order to develop educational and infrastructural interventions, and
was informed by a chart review documenting where the greatest
periods of delay occurred. Ongoing monitoring of treatment times
will allow for continuous quality improvement to occur. The
methodology used in this project can act as a template for other
institutions wishing to identify their own site-specific barriers to
prompt treatment, while the interventions developed will be eval-
uated in future studies for their effectiveness on decreasing delays
within this institution. This quality improvement study provides a
mixed methodology model for improving process efficiency and
developing ‘‘best-practice’’ targets in the treatment of FN.
ACKNOWLEDGMENT
This study was funded by an education grant from the C17
Council. The funding agency had no role in the conduct of the
study or the writing of this manuscript. The authors would like to
acknowledge Ms. Marie Pinard for her thoughtful review of the
project and manuscript. The authors would also like to acknowl-
edge Dr. Stephen Porter and Dr. Jim Whitlock for their comments.
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