ORIGINAL ARTICLE
Improved Diagnosis and Treatment of Bone and Joint
Infections Using an Evidence-based Treatment Guideline
Rachel D. Quick, RN, MSN, CNS,* John Williams, MD,† Marisol Fernandez, MD,‡
Hilton Gottschalk, MD,† Peter Cosgrove, MBBChBAO,§ Kyle Kahlden, MD,∥
Kathryn Merkel, PharmD, BCPS (AQ-ID), BCPPS,¶ Lynn Thoreson, DO,#
Patrick Boswell, BA,** and Sarmistha B. Hauger, MD‡
Background: Our institution created a multidisciplinary guideline
for treatment of acute hematogenous osteomyelitis (AHO) and
septic arthritis (SA) in response to updates in evidence-based
literature in the field and existing provider variability in treat-
ment. This guideline aims to improve the care of these patients by
standardizing diagnosis and treatment and incorporating up to
date evidence-based research into practice. The primary objective
of this study is to compare cases before versus after the im-
plementation of the guideline to determine concrete effects the
guideline has had in the care of patients with AHO and SA.
Methods: This is an Institutional Review Board-approved retro-
spective study of pediatric patients age 6 months to 18 years hospi-
talized between January 2009 and July 2016 with a diagnosis of AHO
or SA qualifying for the guideline. Cohorts were categorized: pre-
guideline and postguideline. Exclusion criteria consisted of: symptoms
> 14 days, multifocal involvement, hemodynamic instability, sepsis, or
history of immune deficiency or chronic systemic disease. Cohorts
were compared for outcomes that described clinical course.
Results: Data were included for 117 cases that qualified for the
guideline: 54 preguideline and 63 postguideline. Following the suc-
cessful implementation of the guideline, we found significant decrease
in the length of intravenous antibiotic treatment (P < 0.001), decrease
in peripherally inserted central catheter use (P < 0.001), and an in-
crease in bacterial identification (P = 0.040). Bacterial identification
allowed for targeted antibiotic therapy. There was no change in
From the *Pediatric Infectious Diseases; **Clinical Quality and Opera-
tional Effectiveness, Dell Children’s Medical Center of Central Texas;
†Central Texas Pediatric Orthopedics, Dell Children’s Medical Cen-
tral of Central Texas, University of Texas at Austin Dell Medical
School; ‡Pediatric Infectious Diseases, University of Texas at Austin
Dell Medical School, Dell Children’s Medical Center of Central
Texas; ∥University of Texas at Austin Dell Medical School, Dell
Children’s Medical Center of Central Texas; ¶Department of Phar-
macy, Dell Children’s Medical Central of Central Texas; #Dell
Children’s Medical Central of Central Texas, University of Texas at
Austin Dell Medical School, Austin, TX; and §Emergency Depart-
ment, Boston Children’s Hospital, Boston, MA.
None of the authors received financial support for this study.
The authors declare no conflicts of interest.
Reprints: Rachel D. Quick, RN, MSN, CNS, Dell Children’s Medical
Group, Pediatric Infectious Diseases, 1301 Barbara Jordan Boule-
vard, Austin, TX 78723. E-mail: rdquick@ascension.org.
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/BPO.0000000000001187
J Pediatr Orthop  Volume 00, Number 00, ’’ 2018
Copyright r 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
length of hospital stay or readmission rate after the implementation
of the guideline.
Conclusion: Utilizing an evidence-based treatment guideline for
pediatric acute hematogenous bone and joint infections can lead
to improved bacterial diagnosis and decreased burden of treat-
ment through early oral antibiotic use.
Level of Evidence: Level III– retrospective comparative study.
Key Words: acute hematogenous osteomyelitis, septic arthritis,
pediatric, guideline
(J Pediatr Orthop 2018;00:000–000)
A cute hematogenous osteomyelitis (AHO) and septic ar-
thritis (SA) are caused by blood borne bacteria that seed
highly vascularized growing bones in children.1,2 Yearly
incidence of AHO among children in developed countries is
8 per 100,000, with preponderance in boys.1,2 When treated,
prognosis is favorable with a recurrence rate of <5%.1
In the absence of a coordinated team approach, many
aspects of care for children with AHO and SA have been
inconsistent or unnecessary. In the past, the work-up of patients
with presumed osteomyelitis has relied on numerous imaging
and laboratory studies with inconsistent use of focal biopsy.
Children frequently present with vague symptoms, and are
often evaluated by emergency room physicians and pediatric
hospitalist services. Orthopaedic surgery may become involved
if there is a positive finding on imaging, and to determine the
need for a focal biopsy. If the child was previously anesthetized
for magnetic resonance imaging (MRI), a focal biopsy is
often avoided. Without a focal biopsy, empiric long-term in-
travenous (IV) therapy is often used to ensure broad-spectrum
antibacterial coverage. The lack of coordination of care may
result in delayed and incomplete diagnosis, and frequent use
of peripherally inserted central catheters (PICCs) for empiric
therapy.
Current level III evidence supports a multidisciplinary
team approach to the diagnosis and management of children
with bone and joint infections, to streamline the diagnostic
work-up, improve efficiency, and increase the rate of identi-
fying a causative organism.3–5 Initial evaluation should include
laboratory studies, including C-reactive protein (CRP), eryth-
rocyte sedimentation rate and blood cultures, radiographs, and
MRI scanning of the affected extremity.5–9 Standardized MRI
www.pedorthopaedics.com |1
Quick et al
time scheduling has been shown to improve coordination
between medical and surgical teams and promote routine focal
biopsy immediately following MRI scanning.3 In addition to
performing routine culture on biopsy specimens, polymerase
chain reaction (PCR) testing has been shown to increase
bacterial identification in patients with osteomyelitis.10
Although IV antibiotic therapy has been used suc-
cessfully to treat children with bone and joint infections,
there are frequent complications associated with long-term
indwelling catheters.11 Current evidence supports early
transition to oral antibiotic therapy (< 5 d) for uncomplicated
acute osteomyelitis.12–20 Improved bacterial identification
allows for targeted antibiotic therapy directed toward a spe-
cific pathogen.6,11 However, evidence is lacking to determine
optimal duration of IV therapy as well as measurements of
clinical response to guide this transition.
METHODS
In September of 2013, our hospital, a 240-bed free-
standing children’s hospital, created and implemented an
evidence-based, multidisciplinary, diagnosis, and treat-
ment guideline for acute hematogenous bone and joint
infections. This study is a retrospective before and after
cohort study designed to evaluate changes occurring as a
result of the guideline.
Guideline Description
The guideline at our institution was created and
implemented by a multidisciplinary team that consisted of
pediatric emergency department physicians, hospitalists,
orthopaedists, infectious disease specialists, radiologists,
anesthesiologists, pharmacists, and representatives from
quality improvement teams. Evidence-based literature was
reviewed by each specialty in the development of the
guideline and evaluated for levels of evidence and practical
utility. Figure 1 portrays a flowchart, which represents the
visual pathway portion of the larger guideline.
Our guideline was designed to engage orthopaedics and
infectious disease early in the hospitalization with hopes of
directing an efficient diagnostic work-up and treatment plan
of care. All patients were managed on the pediatric hospitalist
service with orthopaedic consultation on admission. The
guideline was then initiated immediately upon presentation of
AHO or SA and both orthopaedic and infectious disease
services continued to follow patients with daily rounding until
discharge. Initial laboratory studies, including blood culture,
complete blood count, metabolic panel, CRP, erythrocyte
sedimentation rate, and plain films of the suspected site of
infection were completed upon admission.
MRI is the imaging of choice with the highest sensitivity
for AHO, and therefore was the preferred imaging modality
in the guideline.21,22 To expedite the diagnostic process and
eliminate the need for multiple anesthesia exposures, a 6 AM
time slot was reserved for MRI scanning followed by an
operating room time slot. This facilitated the surgeon per-
forming a focal biopsy or incision and drainage when MRI
findings were positive without the need for additional anes-
thesia. Focal cultures in bone and joint infections are more
likely to be positive than blood cultures in cases of AHO and
2 | www.pedorthopaedics.com
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J Pediatr Orthop  Volume 00, Number 00, ’’ 2018
SA.11 In the case of negative cultures at 48 hours, PCR testing
was performed for Staphylococcus aureus and Kingella kingae
as appropriate for age.
Empiric IV antibiotics were started at the discretion of
the hospitalist service or when MRI findings were positive.
Specific empiric antibiotics were based upon the established
likely causative bacteria in bone and joint infection as well as
our hospital antibiogram (Fig. 1). Clindamycin and ceftriaxone
were used in patients <3 years of age, and clindamycin alone
was used for patients ≥ 3 years. Once an organism was
identified, antibiotic therapy was narrowed, emphasizing
responsible antibiotic use based on specific identified bacteria
and susceptibilities. Cases with identified methicillin-sensitive
Staphylococcus aureus (MSSA) were transitioned to IV
oxacillin or oral (PO) cephalexin; cases of K. kingae were
transitioned to IV ceftriaxone or PO amoxicillin-clavulanate
potassium. Use of additional antibiotic options required
infectious diseases approval. The guideline recommended
patients be converted to oral antibiotics when the following
criteria were met: (1) confirmed diagnosis of uncomplicated
AHO, (2) clinical improvement of signs and symptoms, (3)
afebrile at least 48 hours, (4) CRP decreased from 50% of initial
CRP, and (5) received at least 72 hours of IV antibiotics.
As a part of the quality improvement process,
quarterly multidisciplinary team meetings were held to
ensure compliance with the guideline protocols.
Guideline Evaluation
This is an Institutional Review Board-approved retro-
spective study of pediatric patients age 6 months to 18 years
hospitalized between January 1, 2009 and December 31, 2016
with a diagnosis of AHO or SA that met guideline inclusion
criteria. Cohorts were categorized: preguideline and post-
guideline.
Guideline inclusion criteria included previously healthy
children age 6 months to 18 years of age with a diagnosis AHO
or SA, and fewer than 14 days of symptoms. Exclusion criteria
consisted of: symptoms > 14 days, evidence of sepsis or he-
modynamic instability, contiguous osteomyelitis, complicated
infection, or history of immune deficiency or chronic systemic
disease (Fig. 1). Charts were identified using International
Classification of Diseases, Ninth Revision (ICD-9) and
corresponding ICD-10 diagnosis codes, including 730, 730.0,
730.2, 730.8, 730.9, and 711.0. Cases were then manually
reviewed for inclusion and exclusion.
Chart reviews were performed by the multidisciplinary
team and entered into a REDCap database.23 Variables in-
cluded demographic information, days of symptoms, adher-
ence to the guideline in terms of MRI timing, laboratory
collection timing, initial antibiotics, orthopaedic surgery
consultation, results of cultures and PCR testing, antibiotic
treatment, and readmission for osteomyelitis or PICC line
complication within 30 days. Variables were compared pre-
guideline and postguideline implementation including the rate
of bacterial identification, use and duration of IV versus
PO antibiotics, and PICC line usage. The overall goal of the
algorithm was to achieve meaningful improvements to care
while maintaining aims set forth by the Institutes of Medicine
for health care including treatment that is effective, efficient,
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J Pediatr Orthop  Volume 00, Number 00, ’’ 2018
FIGURE 1. Acute hematogenous bone and joint infection pathway.
equitable, and safe.24 Outcomes to measure this included
length of stay and readmission rate. Continuous variables were
analyzed using Wilcoxon rank sum, medians, and interquartile
range. χ2 and Fisher exact tests were used depending on the
sample size in each category, with 95% confidence intervals
and a P-value <0.05 being considered significant.23,25
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Improved Diagnosis and Treatments of Bone and Joint infections
RESULTS
Charts reviewed identified 117 patients with a diag-
nosis or AHO or SA that qualified for the study and were
included in this report; 54 preguideline, and 63 postguide-
line. Patient characteristics were comparable in both groups
(Table 1). There was gradual acceptance and adherence to
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Quick et al J Pediatr Orthop  Volume 00, Number 00, ’’ 2018

bacteria identified largely responded well to empiric IV

TABLE 1. Demographic and Outcomes
antibiotics. Vancomycin was added in 3 culture-negative
Preguideline Postguideline cases throughout the study period for which symptoms did
(N = 54) (N = 63) P
not resolve when treated empirically.
Age [median (IQR)] (y) 6.2 (1.8-9.7) 5.95 (2.1-9.7) 0.870 Application of guideline criteria for early transition to
Sex (male) [n (%)] 34 (63) 33 (48) 0.334 oral antibiotic management shortened the length of IV anti-
Length of stay [median (IQR)] 4.5 (3.6-5.5) 4.9 (3.8-5.7) 0.165
Readmission rate [n (%)] 6 (12.5) 6 (10.5) 1.000 biotics and significantly decreased PICC line usage (Figs. 3,
MRI done within 24 h [n (%)] 36 (67) 52 (83) 0.077 4). The guideline at our hospital does not differentiate
Bacterial identification by 24 (44) 41 (65) 0.040 between SA and AHO in terms of initial work-up and empiric
culture or PCR [n (%)] treatment. Although not specified in the guideline, duration of
IV antibiotic days 22 (15-29) 5 (4-21) < 0.001
[median (IQR)]
antibiotic treatment differed between SA and AHO cases with
Oral antibiotic days 14 (0-14) 21 (14-28) < 0.001 SA cases being treated a median of 28.5 days and AHO
[median (IQR)] 33 days overall (P = 0.010). During the hospitalization, initial
PICC utilization [n (%)] 49 (91) 28 (44) < 0.001 and final CRP values were collected to determine the percent
IOR indicates interquartile range; IV, intravenous; MRI, magnetic resonance decrease in CRP, which was part of discharge criteria on the
imaging; PCR, polymerase chain reaction; PICC, peripherally inserted central guideline. Postguideline, among those with an elevated initial
catheter. CRP ( > 1 mg/L), the CRP had decreased by at least 50% at
the time of discharge in 85% of cases. Other cases were
discharged due to resolution or improvement of symptoms
and evidence of decreasing CRP even though they did not
the algorithm, after its implementation, with most MRIs
meet the 50% decrease criteria. CRP values were not
performed within the first 24 hours of admission, leading to
consistently performed before the guideline and therefore
prompt focal biopsy when clinically indicated (Table 1). The
this variable was not a good candidate for evaluation of the
increase in early focal biopsies, blood cultures, and PCR
guideline or speed of CRP normalization. There was no
testing facilitated a significant increase in the identification of
change in length of hospital stay or readmission rate after the
bacterial etiology (Fig. 2). Bacterial identification was
implementation of the guideline.
improved, particularly among cases with K. kingae
infection as a result of adding PCR testing in cases with
negative culture results. Among those with an identified DISCUSSION
MSSA or K. kingae, all cases received targeted antibiotics in The use of a diagnosis and treatment guideline with
accordance with the guideline recommendations. Focused standard timing for MRI and focal aspiration has im-
antibiotics therapy according to the guideline for MSSA proved coordination of care for patients with osteomyelitis
include oxacillin IV therapy transitioning to cephalexin oral at our institution. Our findings are similar to those seen in
therapy; for K. kingae ceftriaxone IV therapy transitioning to other reports where a multidisciplinary team manages
amoxicillin/clavulanate oral therapy. In addition, changes patients with osteomyelitis using an evidence-based
were made to antibiotics in cases with identified bacteria that guideline.3,4
were not susceptible to recommended antibiotics or bacteria Although we feel our findings support the overall
identified other than MSSA or K. kingae. Cases with no results in the literature, available studies involve slightly

Pre Guildeline (n=54) Post Guideline (n=63)

MRSA
MRSA
2%
6%

MSSA
MSSA 32%
33% No
No Bacteria
Bacteria found
found 35%
GAS
55%
GAS 10%
4%
Kingella Kingella
Other Kingae Other Kingae
4% 2% 6% 11%

FIGURE 2. Bacterial identification by culture and polymerase chain reaction. GAS indicates Group A Streptococcus; MRSA,
methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.

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J Pediatr Orthop  Volume 00, Number 00, ’’ 2018 Improved Diagnosis and Treatments of Bone and Joint infections

Proportion of Patients with a PICC line
120%
100% 100% 100%
93%
80%
67%
60%
40%
20%
0%
2009 2010 2011 2012
Proportion of Patients with a PICC line
FIGURE 3. Peripherally inserted central catheter (PICC) line
utilization by year: 2009 to 2016.
different populations and outcomes. We did not see a
decrease in length of stay as in the case of other reports,
however, our initial length of stay was already quite low in
comparison.3–5 Copley and colleagues included a wider
subset of cases than our algorithm, which restricts cases to
noncomplex presentation. This accounts for a longer
length of stay in that study. Our population is most similar
to the Spruiell and colleagues study in which preguideline
length of stay was longer than in our data, but post-
guideline length of stay was nearly identical to our data.
Likewise, this study found decreased IV therapy days,
increased PO therapy days, decreased central line use, and
increased pathogen identification. This study resulted in a
decreased related readmission rate and ours did not,
though there is trend of decreasing readmissions.4
Pediatric orthopaedic service involvement immediately
upon admission improves communication with emergency
department physicians and pediatric hospitalists and allows
the surgeon to formulate a timely diagnosis and treatment
plan. The prearranged early morning time slot for MRI and
reserved operating room facilitates the surgeon’s availability
to perform focal biopsy, and drainage procedures immedi-
ately following a positive MRI. Utilizing this type of
multidisciplinary team approach to imaging and surgical
30
25
Days of Antibiotics
intervention has been shown to decrease the duration of
MRI exposure and risk of multiple sedations.26 At our in-
stitution, the number of patients receiving MRI scans within
24 hours of admission has gradually increased as all services
became more conversant with the guideline.
71% Our increased utilization of focal biopsies and PCR
50%
testing has resulted in a significant improvement in bac-
46% terial identification. PCR testing of culture-negative
31% specimens has previously been shown to increase bacterial
Guideline Roll-Out identification.27 K. kingae species is a fastidious organism,
often difficult to culture, and represented the largest in-
2013 2014 2015 2016 crease in identification in our study (Fig. 2).28
With increased bacterial identification, we were able to
establish a treatment algorithm, using our local antibiogram.
Infectious disease and orthopaedic surgery consultants worked
together to standardize initial empiric IV antibiotic therapy to
cover a wide variety of pathogens, including MRSA. Once
cultures are obtained, the pathway guides early conversion to
oral antibiotics, using targeted antibiotic choice for identified
bacteria. In light of increasing antimicrobial resistance, this
type of responsible antibiotic use is preferred over long-term
empiric therapy.22 Of note, with evolving resistance patterns
and differences regionally, it is important to make decisions
for empiric antibiotics based on continued assessment of local
antibiotic resistance patterns to guide treatment and update
algorithms like the one represented here.
There was a significant decrease in the use of PICC
lines (Fig. 3), and at the time of this analysis nearly 69% of
patients with AHO or SA are being discharged home on oral
antibiotics. Before the onset of our guideline, patients typically
stayed in hospital an average of 5 days and were discharged
home on IV antibiotics often without definitive diagnosis.
Currently, there is no statistically significant change in hospital
length of stay; however, most patients are discharged home
with a specific bacterial diagnosis and a course of PO
antibiotics directed at the infecting organism.
The management of a child at home on oral anti-
biotics is greatly preferred over home IV antibiotic ad-
ministration with less likelihood of PICC line associated
complications and readmissions.29 It is very possible that
the increased use of oral antibiotics rather than prolonged
IV therapy with PICC lines may have a positive financial
impact on families, but this will need to be the topic of
future study.
In conclusion, we found that utilization of an evi-
dence-based treatment guideline for pediatric acute hem-
atogenous bone and joint infections can lead to improved

20
bacterial diagnosis and decreased burden of treatment
15
through early oral antibiotic use and less reliance on PICC
lines for long-term IV therapy without negative effect on
10 length of stay or readmission rate.

5 Areas of Future Research

Guideline Roll-Out
There is clearly a subset of pediatric patients with much
0
2009 2010 2011 2012 2013 2014 2015 2016
more serious bone and joint infections. These patients often
present with chronic symptoms and/or multifocal involvement
Median PO Days Median IV Days
and may have signs of sepsis or hemodynamic instability. They
FIGURE 4. Median days of oral and intravenous antibiotics: often will require multiple surgical procedures and supportive
2009 to 2016. intensive care unit care. The use of a multidisciplinary

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Quick et al
approach with early orthopaedic surgery involvement and
standardized MRI scheduling and biopsy has most likely im-
proved the overall coordination of care of these patients at our
institution. Athey et al7 have recently published data validating
a scoring system to determine the likely severity of AHO in
children. Although this group of more complex patients was
not included in this study, we are currently evaluating whether
improved bacterial identification can provide targeted anti-
biotic therapy, and thus reduce the duration of IV therapy, and
hope to incorporate this data with existing literature to con-
tribute to this dynamic field of medicine.
ACKNOWLEDGMENTS
The authors acknowledge the work the following
persons for the work in chart review: Ryan Schexnaidre,
John McNamara, and Michelle Ghebranious.
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