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Pharmacology
Column Editor: Kyle A. Weant, 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
23
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Article: AENJ-D-14-00038 Date: January 16, 2015 Time: 23:9
of open fracture wounds (Gustilo & Ander- inoculums acquired during or following in-
son, 1976). In an attempt to limit this un- jury, this does not necessarily represent the
toward consequence, antibiotic prophylaxis bacteria that subsequently results in infec-
is commonly used to limit the rate of infec- tion (Patzakis, Harvey, & Ivler, 1974). Mul-
tious complications. However, the benefits of tiple studies utilizing wound cultures have
this practice need to be critically weighed found that bacteria found in these wounds
against the known risks of prophylactic an- at the time of presentation do not correlate
tibiotic use, such as the development of an- with bacteria that subsequently cause postop-
tibiotic resistance, subsequent infection from erative infections in these patients (Carsenti-
multidrug resistant pathogens, and the de- Etesse et al., 1999; Lee, 1997; Merritt, 1988).
velopment of a health care associated infec- Blood cultures have also been found to be
tion (Manian, Meyer, Setzer, & Senkel, 2003; equally unhelpful, with only 8% correlating
Namias et al., 1999). The emergent manage- with subsequent infectious organisms (Lee,
ment of these fractures includes stabilization, 1997). Most infections of open fractures tend
debridement, irrigation, soft tissue coverage, to be the result of hospital-acquired bacte-
and systemic antibiotic prophylaxis. Emer- ria including gram-negative rods and gram-
gency department practitioners are encour- positive staphylococci. Some studies have re-
aged to develop standardized approaches to ported nosocomial bacteria to be responsible
this patient population to ensure the provi- for as many as 92% of infections (Carsenti-
sion of safe, timely, and effective antibiotic Etesse et al., 1999). This is likely secondary
prophylaxis. This review will discuss the eti- to immunosuppression due to the injury itself
ology and factors associated with the de- as well as alterations in perfusion to the in-
velopment of infections in this setting, the jured tissue (Barie, 2006). This is supported
use of empiric antibiotics, and the available by studies that have shown that the time
guidelines. to definitive treatment did not have an im-
pact on the infection rate; however, infection
rates were significantly increased in more se-
ETIOLOGY
vere fractures (Gustilo, & Anderson, 1976).
The occurrence of infections with open frac- Historically, gram-positive organisms includ-
tures is a potentially preventable deleterious ing Staphylococcus aureus accounted for as
adverse event. The rate of infection is quite much as half of all surgical site infections in
variable but has been noted to be up to the setting of open fractures (Bergman, 1982;
50% in some studies (Carsenti-Etesse et al., Braun, Enzler, & Rittmann, 1987; Patzakis et
1999). Certain subpopulations within those al., 1974). More recent research in the age
presenting with open fractures also appear of a higher prevalence of methicillin-resistant
to be more predisposed to the development Staphylococcus aureus (MRSA) has found
of infection (Lane et al., 2012). Patients who that although the overall causative agent has
present with a more severe fracture grade, not changed, MRSA now accounts for a sub-
defined by the Gustilo and Anderson scale, stantial portion of this number (up to 18%)
have a statistically significant increased inci- (Saveli et al., 2013). This rate has also been
dence of infection (Harley, Beaupre, Jones, noted to increase significantly in those who
Dulai, & Weber, 2002; Hauser et al., 2006). have nasal colonization with MRSA (Saveli
The impact of a subsequent infection can also et al., 2013; Shukla, Nixon, Acharya, Korim, &
be profound as the rate of infection has been Pandey, 2009). Approximately 20% of the gen-
shown to increase the incidence of nonunion eral population has nasal colonization with
of the fracture and subsequent bone insta- S. aureus and it can persist for months or
bility (Gustilo & Anderson, 1976). Although years (Weidenmaier, Goerke, & Wolz, 2012).
many patients with open fractures present In one study of open fractures, more than 20%
to the ED with a certain amount of bacterial of patients were found to be colonized with
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Article: AENJ-D-14-00038 Date: January 16, 2015 Time: 23:9
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Article: AENJ-D-14-00038 Date: January 16, 2015 Time: 23:9
Table 1. Estimated infection rate by fracture grade and recommended antibiotic coverage
Surgical Infection
Infection Society
Fracture grade rate EAST recommendations recommendations
Note. EAST = Eastern Association for the Surgery of Trauma. From “Epidemiology of Bacterial Infection During Man-
agement 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.
315–323; “East Practice Management Guidelines Work Group: Update to Practice Management Guidelines for Prophy-
lactic 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. 751–754; “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. 379–405.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Article: AENJ-D-14-00038 Date: January 16, 2015 Time: 23:9
in Type III open fractures (Hoff et al., 2011). ment of possible Clostridium contamination
Those fractures that may have fecal or poten- is based on insufficient evidence. They do
tial Clostridium contamination, such as farm- agree with the EAST guidelines in stating that
related injuries, should also have additional there are inadequate data to suggest that the
high-dose penicillin added for coverage. Re- use of prolonged regimens of prophylactic an-
garding duration of therapy, the EAST guide- tibiotics past the initial preoperative period is
lines recommend that antibiotics be discon- beneficial in any way.
tinued 23 hr after wound closure for Type I Although these two sets of guidelines pro-
and II fractures and that they be continued vide some contradictory recommendations, it
for 72 hr for Type III fractures or not greater is clear that early administration of agents di-
than 24 hr subsequent to soft tissue coverage rected at gram-positive bacteria is indicated
of the wound. soon after the presentation of an open frac-
Research looking into overall use of these ture. The timing of this administration can be
guidelines has demonstrated low rates of com- quite critical. One study conducted by Patza-
pliance. Barton and colleagues conducted a kis and Wilkins (1989) found that there was
retrospective analysis of 214 patients and an increase in infection rate by 3.7% when
found that the prescription of prophylactic antibiotics were delayed by more than 180
antibiotics was guideline compliant in 28.5% min. These data are in line with the opinions
of patients (Barton, McMillian, Crookes, of those of the Orthopaedic Trauma Associa-
Osler, & Bartlett, 2012). The most common tion that found that a survey of its members
reason noted for noncompliance was the use showed that they felt that less than 60 min
of coverage that exceeded the suggested du- should be the antibiotic administration tar-
ration (71.2%). The most common antibiotics get for this presentation (Obremskey et al.,
used were cefazolin (46.7%) and cefazolin 2013). To improve early and appropriate an-
plus gentamicin (36.4%). The authors found tibiotic administration in this select popula-
that noncompliance with the EAST guidelines tion, one group even devised an approach
was associated with statistically significant in- that involved audiovisual presentations, ed-
creases in in-hospital morbidity. They noted ucational posters, increased antibiotic avail-
increases in intensive care unit length of stay, ability, and continuous performance feedback
hospital length of stay, number of surgical pro- to enhance care (Collinge, McWilliam-Ross,
cedures performed, and the number of units Kelly, & Dombroski, 2014). Through this mul-
of packed red blood cells transfused. tipronged approach, the authors significantly
The Surgical Infection Society (SIS) has also increased antibiotic administration within
developed an evidence-based guideline re- 1 hr by 28% and improved recommended
garding prophylactic antibiotic use in open dosing of antibiotics by 12%. Another group
fractures (Hauser et al., 2006). The SIS implemented an evidence-based protocol for
guidelines recommend that first-generation prophylaxis that significantly decreased the
cephalosporins (e.g., cefazolin), or an agent use of aminoglycoside and glycopeptide an-
that provides similar coverage against gram- tibiotics by 37.1%, with no increase in skin
positive bacteria, are indicated for 24–48 hr and soft tissue infection rate (Rodriguez et al.,
perioperatively for Grade I–III fractures. In a 2014).
deviation from the EAST guidelines, the SIS
guidelines state that there are insufficient data
CONCLUSION
to conclude that it is necessary to provide
antibiotics providing coverage against gram- Traumatic injury resulting in an open fracture
negative bacteria (e.g., aminoglycosides, flu- is a frequent presentation to EDs. The signif-
oroquinolones) as prophylaxis for any grade icant morbidity that can be traced to these
of open fracture. Furthermore, they state that injuries is often secondary to infection. Al-
the use of prophylactic penicillin for the treat- though these wounds are often contaminated
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Article: AENJ-D-14-00038 Date: January 16, 2015 Time: 23:9
by multiple organisms on presentation, the phylactic antibiotic administration for open fracture
majority of open fracture infections are due patients: Results of a performance improvement pro-
gram. Journal of Orthopaedic Trauma, 28, 620–
to gram-positive organisms. As such, the pro-
625. doi:10.1097/BOT.0000000000000090
vision of antibiotic prophylaxis as soon as Gosselin, R. A., Roberts, I., & Gillespie, W. J.
possible after injury is recommended by the (2004). Antibiotics for preventing infection in
available guidelines. Although the addition of open limb fractures. The Cochrane Database
gram-negative coverage and high-dose peni- Systematic Reviews, (1), CD003764. doi:10.1002/
14651858.CD003764.pub2
cillin is debatable, the early administration of
Griffin, M., Malahias, M., Khan, W., & Hindocha,
an antibiotic with coverage against MSSA is S. (2012). Update on the management of open
clearly indicated. Regardless of the specific lower limb fractures. Open Orthoedics Jour-
antibiotics chosen for prophylaxis, these med- nal, 6 (Suppl 3:M13), 571–577. doi:10.2174/
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est period possible, as the extended use of Gustilo, R. B., & Anderson, J. T. (1976). Prevention
of infection in the treatment of one thousand and
these agents has been shown to propagate an- twenty-five open fractures of long bones: Retrospec-
tibiotic resistance and increase the risk of in- tive and prospective analyses. The Journal of Bone
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