a b s t r a c t

Objective: The objective of the study was to assess the impact of a computer physician Order entry (CPOE) elec- tronic order set on appropriate vancomycin dosing in the emergency department (ED).

Methods: We conducted a retrospective study examining ED dosing of vancomycin before and after the imple- mentation of an electronic weight-based vancomycin order set. Preimplementation and postimplementation pa- tient records were analyzed between the dates of June 1st and August 31st 2010 for the pre-CPOE group and January 1st to March 31st 2013 for the post-CPOE group.

Statistical analysis: ?² analysis, Fisher exact test, and t tests were performed with a 2-sided P value b.05 denoting statistical significance, where appropriate.

Results: A total of 597 patients were included in the study, with 220 in the pre-CPOE group and 377 in the post- CPOE group. The use of the electronic order set resulted in a 21.9% increase (P b .05) in appropriate dosing with 67.4% (254/377) of post-CPOE vancomycin doses considered appropriate vs 45.5% (100/220) in the pre-CPOE group. In critically ill patients, there was a 16.3% increase in appropriate dosing with 44.7% (38/85) in the post- CPOE group compared with 28.4% (19/67) in the pre-CPOE group.

Conclusion: The implementation of an electronic order set increased the percentage of ED patients receiving ap- propriate initial vancomycin doses. The impact of increasing compliance to vancomycin guidelines is in accor- dance with stewardship principles that promote optimization of antimicrobial dosing based on individual patient characteristics. More studies are needed to assess the relationship between appropriate vancomycin loading doses in the ED and therapeutic outcomes.

(C) 2014

Introduction

Vancomycin is the most commonly used antibiotic for the treatment of gram-positive infections and has become the mainstay for empirical methicillin-resistant Staphylococcus aureus coverage. Because the emer- gency department (ED) is often the initiator of empirical antibiotic ther- apy, proper initial ED dosing is vital to achieve therapeutic levels [1]. Unfamiliarity with both vancomycin pharmacokinetics and recent guidelines may lead to subtherapeutic dosing in the ED, where patients often receive a standard 1000 mg initial dose. To help guide vancomycin dosing practices, a joint consensus statement authored by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists was re- leased in 2009 [2]. These guidelines suggest initial doses of vancomycin 15 to 20 mg/kg of actual body weight and to consider higher doses in critically ill patients [2]. With increasing heterogeneity of our current

? Funding: None to disclose.

?? Prior presentations: None.

* Corresponding author at: Lakeland Hills Blvd Lakeland, FL 33805. Tel.: +1 863 701 4485 1324.

E-mail address: [email protected] (A.B. Hall).

population, a standard 1000 mg dose is often under the suggested weight-based dosing recommendation [3]. Inappropriate vancomycin dosing may lead to delays in therapeutic serum trough concentrations, the emergence of vancomycin resistant pathogens, and may ultimately culminate in treatment failure [4,5]. The purpose of our study was to as- sess the impact of an electronic order set on appropriate initial vanco- mycin dosing in the ED.

Methods

This was a retrospective cohort study of adult patients seen in the ED at a tertiary care hospital with an annual ED census of more than 180000 visits. This study was designed to compare the appropriateness of vancomycin initial dosing before and after the implementation of a vancomycin weight-based electronic order set (Figure). The institution- al review board at “removed for blinding” approved this study. Patients eligible for inclusion in the cohort were those aged 18 years and older who had received a dose of vancomycin in the ED between the periods of June 1, 2010 to August 31, 2010 (precomputer physician order entry [CPOE]) and January 1, 2013 to March 31, 2013 (post-CPOE). The vanco- mycin electronic order set was approved for use in September 2010, and

http://dx.doi.org/10.1016/j.ajem.2014.09.049

0735-6757/(C) 2014

A.B. Hall et al. / American Journal of Emergency Medicine 33 (2015) 92-94 93

Vancomycin Electronic Order Set

Patient less than 50 kg	vancomycin 1000 mg/200 mL D5W IVPB, one time
Patient 50 - 75 kg	vancomycin 1500 mg/D5W 300 mL IVPB, one time

Patient 76 - 100 kg	vancomycin 2000 mg/D5W 400 mL IVPB, one time
Patient > 100 kg	vancomycin 2500 mg/D5W 500 mL IVPB, one time

Figure. Vancomycin electronic order set.

a 2-year period postapproval was chosen to allow for implementation, physician education, and to acquire familiarity with the order set. Pa- tients were excluded if their weight was unable to be determined, or if a pharmacy consult was requested. In cases where the ED pharmacist adjusted the initial dose, the original physician ordered dose was used for analysis. Patients were identified for inclusion by a Cerner Discern Analytics report of ED patients who received intravenous vancomycin. The report also provided patient demographic and clinical information, which included vancomycin dose, patient location, and ordering provider. Other data collected (sex, age, indication, weight, serum creatinine, height, and presence of intensive care unit [ICU] admission) were obtained by further manual review of the electronic medical record (EMR). Data were abstracted by trained doctorate of pharmacy students. Training included orientation to the EMR and how to properly document using the standardized data collection tool. Abstractors were not aware of the intervention being evaluated or the study’s objectives. The primary objective was to compare the rate of appropriate initial ED vancomycin doses between the pre-CPOE and post-CPOE groups. Appropriate vancomycin doses were defined based on our institution’s Adult Vancomycin Protocol, which incorporates pharmacokinetic prin- ciples and recommendations published in the 2009 consensus state- ment. Our institution recommends at least 15mg/kg as the initial dose for most indications and at least 10 mg/kg for urinary sources. Vanco- mycin is highly concentrated in the urine with 90% excreted unchanged, hence lower doses are required to achieve therapeutic benefit [6]. In ad- dition, our institution recommends higher doses in critically ill patients of at least 20 mg/kg or 15 mg/kg for urinary sources. The secondary ob- jective was to compare the appropriateness of initial vancomycin doses in the subset of critically ill patients, defined as those admitted to ICUs from the ED. Study data were analyzed using Fisher exact test, ?² anal- yses, and t tests. All P values presented are 2 tailed and used a P value of

b.05 to denote statistical significance. All statistical analyses were per-

formed using GraphPad statistical software (La Jolla, CA).

Results

A total of 724 patients received an order for vancomcyin during the study periods. Of the 597 patients who met inclusion criteria, 220 were in the pre-CPOE group and 377 in the post-CPOE group. Patient demo- graphic and clinical information are described in Table 1. Age and sex were similar between the pre-CPOE and post-CPOE groups with a mean age of 60.7 years (SD, 18.5) and 61.7 years (SD, 18.6) and males comprising 53.6% and 52.8% of the groups, respectively. The mean weights between the 2 groups were 82.9 kg (SD, 27) and 88.2 kg (SD, 32.2), respectively, with more patients weighing greater than 100 kg in the post-CPOE group. The most common indication for vanco- mycin in both groups was skin and soft tissue infections.

Initial ED vancomycin doses were evaluated based on weight and in- dication with results presented in Table 2. The use of the electronic order set resulted in a 21.9% increase (P b .05) in appropriate dosing with 67.4% (254/377) of vancomycin doses considered appropriate vs

45.5% (100/220) before implementation. In critically ill patients, there was a 16.3% increase in appropriate dosing with use of the electronic order set. In this population, 44.7% (38/85) of doses in the post-CPOE group were considered appropriate compared with 28.4% (19/67) in the pre-CPOE group (P = .04).

Both the overall mean vancomycin dose and doses according to indi- cation were compared between groups. Mean doses compared by indi- cation are detailed in Table 2. There was a significant increase in the overall mean dose of vancomycin, increasing from 14.6 mg/kg (SD, 4.9) to 17.4 mg/kg (SD, 5.7) after electronic order set implementa- tion. All indications experienced significant increases in mean doses except for sepsis, in which doses remained similar between each group at 17.5 mg/kg (SD, 4.7) vs 18.0 mg/kg (SD, 5.4) (P = .72).

Discussion

Although vancomycin has been the leading antibiotic used for the empirical coverage and treatment of methicillin-resistant Staphylococcus aureus infections, a pervasive lack of vancomycin pharmacokinetic un- derstanding exists in the ED [1]. Despite the 2009 consensus statement, clinicians have yet to fully align their practice patterns to suggested weight-based vancomycin doses and to further consider higher loading doses in critically ill patients [7]. Rosini et al [8] found that only 19.6% (47 of 240) of patients received the 15 to 20 mg/kg recommended dose of vancomycin. In fact, 87.5% (210 of 240) of patients received a standard 1000 mg dose in the ED.

Recent evidence has been published to support the use of CPOE sys- tems to improve overall compliance to dosing recommendations for vancomycin. A retrospective study conducted in 2 community academic EDs investigated the appropriateness of vancomycin dosing before and after the implementation of an electronic weight-based order set. They

Table 1

Baseline demographics

Patient characteristics Pre-CPOE Post-CPOE (n = 220) (n = 377)

Age (y), mean (SD) 60.7 (18.5) 61.7 (18.6)

Male, n (%) 118 (53.6) 199 (52.8)

Weight (kilogram), mean (SD) 82.9 (27) 88.2 (32.2)

b50 kg, n (%)	12 (5.5)	22 (5.8)
50-75 kg, n (%)	87 (39.5)	124 (32.9)
76-100 kg, n (%)	75 (34.1)	129 (34.2)
N 100 kg, n (%)	46 (20.9)	102 (27.1)

Serum creatinine (milligrams per deciliter), mean (SD) 2 (2.6) 1.5 (1.6)

Critically ill patients, n (%) 67 (30) 85 (23) Indication, n (%)

Skin and soft tissue 74 (33.6) 138 (36.6)

Pulmonary 44 (20) 111 (29.4)

Sepsis 31 (14.2) 21 (5.7)

Urinary tract 17 (7.7) 42 (11.1)

Others^a 54 (24.5) 65 (17.2)

^a Others: osteomyelitis, meningitis, bacteremia, or fever of unknown origin.

94 A.B. Hall et al. / American Journal of Emergency Medicine 33 (2015) 92-94

Table 2

Results

Pre-CPOE Post- CPOE P

(n = 220) (n = 377)

patients may have been admitted to the ICU for other comorbid condi- tions or monitoring. Lastly, it is possible that variations in practice over the study period could have contributed in part to the increase in appropriate dosing.

Appropriate initial dose, n (%) All ED patients	100 (45)	254 (67)	b.0001	5. Conclusions
Critically ill patients	n = 67	n = 85	.0441

19 (28)		38 (45)
Initial dose per indication (mg/kg), mean (SD)
Overall mean dose	14.6 (4.9)	17.4 (5.7)	b.0001
Skin and soft tissue	13.0 (4.6)	16.3 (5.7)	b.0001
Pulmonary	15.3 (4.5)	18.1 (5.5)	.0031
Sepsis	17.5 (4.7)	18.0 (5.4)	.72
Urinary tract	14.4 (5.4)	17.9 (6.2)	.046
Othersa Initial dose by weight (mg/kg), mean (SD)	14.8 (4.8)	18.0 (5.7)	.0014
b50 kg	23.1 (3.6)	25.7 (5.7)	.107
50-75 kg	17.0 (3.4)	20.1 (4.8)	b.0001
76-100 kg	13.5 (3.7)	16.9 (4.2)	b.0001
N 100 kg	9.6 (3.1)	12.9 (4.4)	b.0001

^a Others: osteomyelitis, meningitis, bacteremia, or fever of unknown origin.

observed a significant improvement in the percentage of patients who received at least 15 mg/kg of vancomycin, 34.9% pre-CPOE and 51% post-CPOE [3]. If increased utilization of CPOE can influence appropriate dosing of vancomycin, patients may achieve target serum vancomycin concentrations at a faster rate, thus reducing the rate of vancomycin re- sistance and failure.

Our study revealed that use of an electronic order set resulted in a 21.9% increase in overall appropriate dosing. Unlike previous studies, our data additionally demonstrated an increase in the rate of appropri- ate initial doses for critically ill patients. Despite a significant increase in initial appropriate dosing, opportunities still exist in the obese popula- tion. Although we observed an improved mean dose in patients weighting greater than 100 kg, the mean dose remained below our tar- get of 15 mg/kg in this group.

The retrospective design of the study may have introduced several limitations. First, the data collected rely on the accuracy of the EMR. There may be outside factors not captured by the EMR that may have contributed to the patient’s care. In addition, ICU admission as a marker for critical illness may not truly represent the severity of illness, as

The use of standardized order sets offers an opportunity for organi- zations to influence prescribing patterns and guide clinicians to partici- pate in evidence-based practice. The adoption of an electronic order set resulted in significant improvement in appropriate initial vancomycin doses in ED patients in addition to those deemed critically ill. The impact of increasing compliance to vancomycin dosing recommendations is in accordance with stewardship principles that promote optimization of antimicrobial dosing based on individual patient characteristics and Pharmacokinetic parameters. More studies are needed to assess the re- lationship between appropriate initial vancomycin doses in the ED and the impact on therapeutic outcomes.

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