Hospital Pharmacy - June 2020 - 195

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Johnson et al
In a recent study, it was found that noncompliance with the
EAST recommendations was associated with increased inhospital morbidity, including increased hospital and intensive
care unit (ICU) lengths of stay (LOSs), number of surgeries
performed, and number of packed red blood cells (PRBCs)
transfused. The most common reason for noncompliance in
this study was the use of guideline-recommended coverage
exceeding the recommended duration.2 The present study
sought to further characterize compliance with EAST guidelines for initial prophylactic antibiotic use in open fractures
and its impact on care.

Materials and Methods
This study was a retrospective analysis of trauma patients,
18 years of age and older, who presented to an academic
medical center emergency department (ED) over a
12-month period with an open fracture. The site was a 569bed acute care academic hospital and Level I trauma center,
with yearly ED visits exceeding 60 000 patients. This protocol was approved by the institution's investigational
review board prior to data collection. Patients were identified via a trauma database. Patients were excluded if they
were discharged from the ED, died within 24 hours of
arrival, received antibiotics prior to arrival, presented with
an open fracture other than that to the extremities, or the
cause of the open fracture was due to penetrating trauma.
The primary objective of this study was to evaluate adherence to the EAST guideline recommendations for prophylactic antibiotics and the appropriateness and timing of
administration of prophylactic antibiotics. For type I and II
fractures, appropriateness was defined as the use of an antibiotic with activity against gram-positive organisms. For
type III fractures, the addition of an antibiotic with gramnegative coverage to a suitable agent for type I and II fractures was deemed appropriate. To facilitate the use of
guideline-appropriate medication use, a protocol had previously been developed for open fracture prophylaxis in the
hospital. Duration of therapy was considered to be guideline compliant for type I and II fractures if an antibiotic
with activity against gram-positive organisms was used for
less than or equal to 24 hours after wound closure.
Prophylactic antibiotics for type III fractures were considered guideline compliant if the fracture was treated for 3
days after the time of injury or not more than 24 hours after
the time of definitive wound closure, whichever occurred
first. For fractures that did not have a grade reported in the
medical record, for the purpose of analysis they were considered to be grade III fractures, thus allowing for the maximal recommended antibiotic duration. Secondary objectives
were to determine whether noncompliance to guideline recommendations affected the number of infectious complications, hospital or ICU LOS, surgeries performed on the
open fracture, or units of PRBCs transfused, as well as to
identify factors associated with an increased infection risk.

Data collected from the patients' medical records included
demographic data, mechanism of injury, fracture type and
location, date and time of presentation, Sequential Organ
Failure Assessment score, timing and dosing of antibiotics
administered in the ED, occurrence of infection, hospital and
ICU LOS, number of inpatient surgeries performed on the
open fracture, and number of PRBCs transfused. At a desired
α of 0.05 and power of 0.8, to detect a >20% relative difference in selection of appropriate prophylactic antibiotic therapy, it was determined that a sample size of approximately
200 patients was necessary. Continuous variables were compared using the Student t test or Mann-Whitney U test, and
dichotomous data were compared using the χ2 analysis or
Fisher exact test where appropriate. Associations between
variables were analyzed using the Spearman rank order correlation. A value of P < .05 was considered statistically significant. All data management was conducted using
Microsoft Office Access, 2007 (Redmond, Washington).
Statistical analysis was conducted using SigmaStat 3.5
Software (Systat Software, San Jose, California).

Results
A total of 370 patients were identified as having an open
fracture. A total of 168 patients were excluded due to receipt
of an antibiotic prior to arrival or presentation with a closed
fracture, leaving 202 open fractures for final analysis.
Multiple open fractures were noted in 9.4% (n = 19) of the
population, with upper extremity fractures present in 36.1%
(n = 73) and lower extremity fractures present in 66.3% (n
= 134) of patients.
No significant differences were noted in baseline characteristics (Table 1). Overall compliance with the EAST trauma
guideline recommendations for antibiotic prophylaxis duration was 33.2%. Table 2 describes the primary and secondary
antibiotic choices, time to initiation, and their duration across
both groups. The initial antibiotic therapy chosen for all
patients in both groups was cefazolin (91.1%), with the most
common dose being 2 g (53%). This distribution was not significantly different between groups. The use of the 2-g dose
was significantly more common in patients ≥80 kg (69.8%)
than those <80 kg (43.2%) (P = .0001). In all, 70.8% of
patients were also prescribed dual antibiotic therapy with a
second antibiotic, most commonly with gentamicin (91.6%)
at an average dose of 4.6 mg/kg total body weight once daily.
This was also not significantly different between groups.
Overall, the average time from ED admission to antibiotic
therapy was 150.4 minutes, and the time to secondary antibiotic administration was 195.6 minutes. No significant difference in the time to antibiotic initiation was noted between
groups. Antibiotic therapy was provided within 1 hour of
admission in 19.8% (n = 40) of patients and within 3 hours in
56.9% (n = 115). No significant difference was found between
the infection rate of those who received prophylaxis within 1
hour of admission and those who received it after (P = .222).

Hospital Pharmacy - June 2020

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