Antibiotic Prophylaxis For Open Fractures in The.4 PDF

Article: AENJ-D-14-00038
Date: January 16, 2015
Time: 23:9
Advanced Emergency Nursing Journal

Vol. 37, No. 1, pp. 2329
C 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright
A P P L I E D
Pharmacology
Column Editor: Kyle A. Weant, PharmD, BCPS
Antibiotic Prophylaxis for Open

Fractures in the Emergency
Department
Kyle A. Weant, PharmD, BCPS
Abby M. Bailey, PharmD, BCPS
Regan A. Baum, PharmD, BCPS
Stephanie B. Justice, PharmD, BCPS
Abstract
Emergency departments across the country regularly treat patients with traumatic injuries. One of
the more common injuries that these patients present with is open fractures. Much of the morbidity
associated with these fractures can be traced to the development of fracture-site infections that can
lead to chronic osteomyelitis, impaired bone healing, and potential limb loss. Initial wound cultures in
this setting are frequently positive, but they tend to demonstrate poor correlation with subsequent
infections. The emergent management of open fractures includes a multipronged approach that
includes stabilization, debridement, irrigation, soft tissue coverage, and systemic empiric antibiotics
for prophylaxis. This review will discuss the etiology and factors associated with the development
of infections in this setting, the use of empiric antibiotics, and the guidelines currently available.
Key words: antibiotics, cefazolin, emergency department, gentamicin, open fracture
NJURIES RESULTING FROM TRAUMA are

a common presentation to emergency departments (EDs) across the United States
and lead to an estimated 5.8 million deaths

per year (Lane, Mabvuure, Hindocha, & Khan,
2012). Open fractures, which are defined as
. . . one in which the fracture fragments communicate with the environment through a
break in the skin, are frequently seen in this
patient population (Hoff, Bonadies, Cachecho, & Dorlac, 2011). Much of the morbidity
associated with these fractures can be traced
to the development of subsequent fracturesite infections that can lead to chronic osteomyelitis, impaired bone healing, and the
potential loss of the limb (Hauser, Adams,
& Eachempati, 2006). Some of the original
research done in this area by Gustilo reported a positive bacterial culture in 70.3%
Author Affiliations: Pharmacy Services, KentuckyOne Health, University of Louisville Hospital and
Jewish Hospital, Louisville, Kentucky (Dr Weant); University of Kentucky HealthCare, and Departments of
Pharmacy Services and Pharmacy Practice and Science,
University of Kentucky College of Pharmacy, Lexington
(Drs Bailey and Baum); and Department of Pharmacy,
Charleston Area Medical Center, Charleston, West
Virginia (Dr Justice).
Disclosure: The authors report no conflicts of interest.
Corresponding Author: Kyle A. Weant, PharmD,
BCPS, Pharmacy Services, KentuckyOne Health, 530
S. Jackson St, Louisville, KY 40202 (kaw9600@alumni
.unc.edu).
DOI: 10.1097/TME.0000000000000052
23
Copyright 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
24
of open fracture wounds (Gustilo & Anderson, 1976). In an attempt to limit this untoward consequence, antibiotic prophylaxis
is commonly used to limit the rate of infectious complications. However, the benefits of
this practice need to be critically weighed
against the known risks of prophylactic antibiotic use, such as the development of antibiotic resistance, subsequent infection from
multidrug resistant pathogens, and the development of a health care associated infection (Manian, Meyer, Setzer, & Senkel, 2003;
Namias et al., 1999). The emergent management of these fractures includes stabilization,
debridement, irrigation, soft tissue coverage,
and systemic antibiotic prophylaxis. Emergency department practitioners are encouraged to develop standardized approaches to
this patient population to ensure the provision of safe, timely, and effective antibiotic
prophylaxis. This review will discuss the etiology and factors associated with the development of infections in this setting, the
use of empiric antibiotics, and the available
guidelines.
ETIOLOGY
The occurrence of infections with open fractures is a potentially preventable deleterious
adverse event. The rate of infection is quite
variable but has been noted to be up to
50% in some studies (Carsenti-Etesse et al.,
1999). Certain subpopulations within those
presenting with open fractures also appear
to be more predisposed to the development
of infection (Lane et al., 2012). Patients who
present with a more severe fracture grade,
defined by the Gustilo and Anderson scale,
have a statistically significant increased incidence of infection (Harley, Beaupre, Jones,
Dulai, & Weber, 2002; Hauser et al., 2006).
The impact of a subsequent infection can also
be profound as the rate of infection has been
shown to increase the incidence of nonunion
of the fracture and subsequent bone instability (Gustilo & Anderson, 1976). Although
many patients with open fractures present
to the ED with a certain amount of bacterial
Time: 23:9
inoculums acquired during or following injury, this does not necessarily represent the
bacteria that subsequently results in infection (Patzakis, Harvey, & Ivler, 1974). Multiple studies utilizing wound cultures have
found that bacteria found in these wounds
at the time of presentation do not correlate
with bacteria that subsequently cause postoperative infections in these patients (CarsentiEtesse et al., 1999; Lee, 1997; Merritt, 1988).
Blood cultures have also been found to be
equally unhelpful, with only 8% correlating
with subsequent infectious organisms (Lee,
1997). Most infections of open fractures tend
to be the result of hospital-acquired bacteria including gram-negative rods and grampositive staphylococci. Some studies have reported nosocomial bacteria to be responsible
for as many as 92% of infections (CarsentiEtesse et al., 1999). This is likely secondary
to immunosuppression due to the injury itself
as well as alterations in perfusion to the injured tissue (Barie, 2006). This is supported
by studies that have shown that the time
to definitive treatment did not have an impact on the infection rate; however, infection
rates were significantly increased in more severe fractures (Gustilo, & Anderson, 1976).
Historically, gram-positive organisms including Staphylococcus aureus accounted for as
much as half of all surgical site infections in
the setting of open fractures (Bergman, 1982;
Braun, Enzler, & Rittmann, 1987; Patzakis et
al., 1974). More recent research in the age
of a higher prevalence of methicillin-resistant
Staphylococcus aureus (MRSA) has found
that although the overall causative agent has
not changed, MRSA now accounts for a substantial portion of this number (up to 18%)
(Saveli et al., 2013). This rate has also been
noted to increase significantly in those who
have nasal colonization with MRSA (Saveli
et al., 2013; Shukla, Nixon, Acharya, Korim, &
Pandey, 2009). Approximately 20% of the general population has nasal colonization with
S. aureus and it can persist for months or
years (Weidenmaier, Goerke, & Wolz, 2012).
In one study of open fractures, more than 20%
of patients were found to be colonized with
JanuaryMarch 2015
r Vol. 37, No. 1
methicillin-sensitive Staphylococcus aureus

(MSSA) and 3% with MRSA (Saveli et al., 2013).
Those with MRSA colonization had a significantly higher rate of subsequent MRSA infections.
The need to provide coverage for gramnegative organisms in the setting of open fractures has been one of significant debate. This
suggestion was initially published for severe
fractures (Grade III) in a seminal paper in the
mid-1970s (Patzakis et al., 1974). However,
limited data have been put forth since this
time to support or refute this claim. The available literature has reported that gram-negative
organisms have been isolated from open fractures in 17%48% of cases (Carsenti-Etesse
et al., 1999; Johnson, Burns, Hayda, Hospenthal, & Murray, 2007; Ong, Choon,
Cabrera, & Maffulli, 2002). Therefore, it is
recommended by some and dismissed by
others leading to substantial variations in
practice (Hauser et al., 2006; Hoff et al.,
2011; Lane et al., 2012). Determining the
need for the provision of this coverage in all
patients, or a specific subset, is critical as the
traditional antibiotic coverage provided in
this setting (e.g., cephalosporins) provides
minimal prophylaxis against these organisms.
EMPIRIC ANTIBIOTIC SELECTION
Wound irrigation, debridement, and delaying
wound closure are the most well-established
methods of decreasing the rate of infection;
however, empiric antibiotics should also be
initiated (see Table 1; Hauser et al., 2006;
Hoff et al., 2011). The high rate of contamination associated with open fractures in the
field has led to the traditional provision of
empiric antibiotics in this setting to prevent
initial infection. As has been discussed, based
on the causative organisms of the subsequent
infections, it is likely that it is the high rate
of contamination of wounds within the hospital that necessitates the use of prophylactic
antibiotics. Regardless of the source, antibiotics have been shown to reduce the risk of
infection by 59%, and so it is clear that some
form of antimicrobial prophylaxis is indicated
Time: 23:9
Open Fracture Prophylaxis
25
in this setting (Gosselin, Roberts, & Gillespie,

2004).
The selection of antibiotics should be
directed at the most likely pathogens as
described previously. Based on the available data, this would translate into coverage for MSSA and possibly gram-negative
organisms (Bergman, 1982; Braun et al.,
1987; Patzakis et al., 1974). The ideal antibiotic regimen is the subject of some debate within the literature, with some recommending only cephalosporin usage and others recommending a combination of both
cephalosporins and aminoglycosides. A systematic review of the literature found that after pooling data from more than 1,000 patients, antibiotics significantly reduced the
incidence of wound infection (Gosselin
et al., 2004). The authors recommend that
the use of prophylactic antibiotics directed
at gram-positive organisms (e.g., cefazolin)
be started as soon as possible after injury
and should be combined with appropriate
wound management to reduce the rate of
subsequent infection. Some European groups
have gone so far as to recommend that antibiotics be administered within the first 3 hr of
injury (Griffin, Malahias, Khan, & Hindocha,
2012).
Clostridium (e.g., Clostridium perfringens) is often a concern in the setting of
a highly contaminated wound in the field,
and historically any wound exposed to dirt
and/or farm soil has received additional coverage against this organism (Griffin et al., 2012).
Many historical articles have recommended
the addition of penicillin G to the antibiotic
regimen in this specific subset of patients
(Patzakis et al., 1974). However, epidemiological data do not appear to support this recommendation, with one study showing that only
a singular Clostridium infection occurred out
of 616 presentations (Carsenti-Etesse et al.,
1999). Furthermore, questions exist regarding the efficacy of the most commonly recommended agent for coverage, penicillin G
(Brazier, Levett, Stannard, Phillips, & Willis,
1985). Therefore, substantial variations regarding this presentation have developed and
Time: 23:9
26
Table 1. Estimated infection rate by fracture grade and recommended antibiotic coverage
Fracture grade
Infection
rate
0%9%
II
1%12%
III
9%55%
Possible fecal or
clostridial
contamination
(e.g., farm-related
injuries)
EAST recommendations
Gram-positive coverage
(e.g., cefazolin)
(e.g., cefazolin)
(e.g., cefazolin) +
Gram-negative coverage
(e.g., gentamicin)
Above coverage plus the
addition of high-dose
penicillin
Surgical Infection
Society
recommendations
(e.g., cefazolin)
(e.g., cefazolin)
(e.g., cefazolin)
No additional coverage
recommended
Note. EAST = Eastern Association for the Surgery of Trauma. From Epidemiology of Bacterial Infection During Management of Open Leg Fractures, by H. Carsenti-Etesse, F. Doyon, N. Desplaces, O. Gagey, C. Tancrede, C. Pradier, B.
Dunais, and P. Dellamonica, 1999, European Journal of Clinical Microbiology and Infectious Diseases, 18(5), pp.
315323; East Practice Management Guidelines Work Group: Update to Practice Management Guidelines for Prophylactic Antibiotic Use in Open Fractures, by W. S. Hoff, J. A. Bonadies, R. Cachecho, and W. C. Dorlac, 2011, Journal of
Trauma, 70(3), pp. 751754; Surgical Infection Society Guideline: Prophylactic Antibiotic Use in Open Fractures: An
Evidence-Based Guideline, by C. J. Hauser, C. A. Jr. Adams, and S. R. Eachempati, 2006, Surgical Infections (Larchmt),
7(4), pp. 379405.
additional studies are needed to resolve this

issue.
Whatever the antibiotic of choice is for the
provision of prophylaxis in this population,
as with all antibiotics, their judicious use is
strongly recommended. Ample evidence exists that demonstrates that the use of prolonged prophylactic antibiotics can lead to
the development of infections with drugresistant organisms in critically ill patients
(Velmahos et al., 2002). This is in addition
to the known potential complication of antibiotic use, C. difficile infection (Lumpkins
et al., 2008). These untoward events can be
mitigated through the use of antibiotics with
a narrow spectrum of activity, administered
for a short amount of time. This decreases the
exposure of bacteria to these agents and limits their ability to develop resistance. Furthermore, with the rising cost, and routine shortages of these agents, it is critical that they be
utilized in a targeted and judicious manner.
REVIEW OF EXISTING GUIDELINES

The Eastern Association for the Surgery of
Trauma (EAST) Practice Management Guidelines Work Group recommends that systemic
antibiotic coverage that specifically targets
gram-positive organisms (e.g., cefazolin) be
started immediately after injury (Hoff et al.,
2011). Furthermore, it recommends the addition of antibiotics with gram-negative coverage for those suffering from Type III fractures because of a higher risk of infection from
that class of organisms. They note that once
daily aminoglycoside (e.g., gentamicin) dosing is both safe and effective for Type II and
III fractures. The EAST guidelines note that
fluoroquinolones (e.g., levofloxacin) offer no
therapeutic advantage over a cephalosporin
plus an aminoglycoside. They go on to further discuss that fluoroquinolones may actually have a negative effect on fracture healing and may result in higher infection rates
JanuaryMarch 2015
r Vol. 37, No. 1
in Type III open fractures (Hoff et al., 2011).

Those fractures that may have fecal or potential Clostridium contamination, such as farmrelated injuries, should also have additional
high-dose penicillin added for coverage. Regarding duration of therapy, the EAST guidelines recommend that antibiotics be discontinued 23 hr after wound closure for Type I
and II fractures and that they be continued
for 72 hr for Type III fractures or not greater
than 24 hr subsequent to soft tissue coverage
of the wound.
Research looking into overall use of these
guidelines has demonstrated low rates of compliance. Barton and colleagues conducted a
retrospective analysis of 214 patients and
found that the prescription of prophylactic
antibiotics was guideline compliant in 28.5%
of patients (Barton, McMillian, Crookes,
Osler, & Bartlett, 2012). The most common
reason noted for noncompliance was the use
of coverage that exceeded the suggested duration (71.2%). The most common antibiotics
used were cefazolin (46.7%) and cefazolin
plus gentamicin (36.4%). The authors found
that noncompliance with the EAST guidelines
was associated with statistically significant increases in in-hospital morbidity. They noted
increases in intensive care unit length of stay,
hospital length of stay, number of surgical procedures performed, and the number of units
of packed red blood cells transfused.
The Surgical Infection Society (SIS) has also
developed an evidence-based guideline regarding prophylactic antibiotic use in open
fractures (Hauser et al., 2006). The SIS
guidelines recommend that first-generation
cephalosporins (e.g., cefazolin), or an agent
that provides similar coverage against grampositive bacteria, are indicated for 2448 hr
perioperatively for Grade IIII fractures. In a
deviation from the EAST guidelines, the SIS
guidelines state that there are insufficient data
to conclude that it is necessary to provide
antibiotics providing coverage against gramnegative bacteria (e.g., aminoglycosides, fluoroquinolones) as prophylaxis for any grade
of open fracture. Furthermore, they state that
the use of prophylactic penicillin for the treat-
Time: 23:9
27
ment of possible Clostridium contamination

is based on insufficient evidence. They do
agree with the EAST guidelines in stating that
there are inadequate data to suggest that the
use of prolonged regimens of prophylactic antibiotics past the initial preoperative period is
beneficial in any way.
Although these two sets of guidelines provide some contradictory recommendations, it
is clear that early administration of agents directed at gram-positive bacteria is indicated
soon after the presentation of an open fracture. The timing of this administration can be
quite critical. One study conducted by Patzakis and Wilkins (1989) found that there was
an increase in infection rate by 3.7% when
antibiotics were delayed by more than 180
min. These data are in line with the opinions
of those of the Orthopaedic Trauma Association that found that a survey of its members
showed that they felt that less than 60 min
should be the antibiotic administration target for this presentation (Obremskey et al.,
2013). To improve early and appropriate antibiotic administration in this select population, one group even devised an approach
that involved audiovisual presentations, educational posters, increased antibiotic availability, and continuous performance feedback
to enhance care (Collinge, McWilliam-Ross,
Kelly, & Dombroski, 2014). Through this multipronged approach, the authors significantly
increased antibiotic administration within
1 hr by 28% and improved recommended
dosing of antibiotics by 12%. Another group
implemented an evidence-based protocol for
prophylaxis that significantly decreased the
use of aminoglycoside and glycopeptide antibiotics by 37.1%, with no increase in skin
and soft tissue infection rate (Rodriguez et al.,
2014).
CONCLUSION
Traumatic injury resulting in an open fracture
is a frequent presentation to EDs. The significant morbidity that can be traced to these
injuries is often secondary to infection. Although these wounds are often contaminated
28
by multiple organisms on presentation, the

majority of open fracture infections are due
to gram-positive organisms. As such, the provision of antibiotic prophylaxis as soon as
possible after injury is recommended by the
available guidelines. Although the addition of
gram-negative coverage and high-dose penicillin is debatable, the early administration of
an antibiotic with coverage against MSSA is
clearly indicated. Regardless of the specific
antibiotics chosen for prophylaxis, these medications should be administered for the shortest period possible, as the extended use of
these agents has been shown to propagate antibiotic resistance and increase the risk of infection because of a drug-resistant organism.
Practitioners in the ED should work to develop standardized approaches to these presentations in order to ensure that appropriate antibiotic therapy is provided in a timely
fashion.
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Article: AENJ-D-14-00038

Date: January 16, 2015

Advanced Emergency Nursing Journal