Assessing the Impact and Feasibility of Pharmacist

Vancomycin Dosing and Monitoring Interventions:

A Pilot Program

Janice Law, BScH, PharmD; Ehsan Haghshenas, BScPhm, ACPR; Hina Marsonia, BScPhm, PharmD;

Sheena Pang, BScPhm, ACPR

1 Department of Pharmacy, William Osler Health System, Brampton, Ontario

BACKGROUND: The benefits of pharmacist-directed vancomycin therapeutic drug monitoring (TDM) on

clinical efficacy, patient safety, and hospital cost-savings are well-described in the literature. However,

there is limited data surrounding the feasibility of implementing such a program.

OBJECTIVES: To evaluate the outcome of pharmacist-directed vancomycin TDM compared to standard

practice and describe the feasibility of its implementation within a large community health system.

METHODS: This was a dual-centre, pre-post study. A vancomycin TDM tool was developed based on

current guidelines and used by pharmacists to intervene within the first 24 hours of vancomycin

initiation. The primary outcomes included rate of trough target attainment, attainment of area under

the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) targets, and the incidence

of nephrotoxicity. Feasibility was assessed by measuring pharmacist intervention rates using a TDM

documentation tool and identifying barriers to implementation.

RESULTS: Eighty-five patient records were retrospectively reviewed during the pre-intervention period.

Forty patients were enrolled during the prospective post-intervention period. Trough target attainment

in the pre- and post-interventions groups were 24.7% and 32.5%, respectively (p=0.361). AUC/MIC

target attainment was 76.5% in the pre-intervention group, compared to 88.9% in the post-intervention

group (p=0.628). Two patients experienced nephrotoxicity; both were in the post-intervention group

(p=0.095). Pharmacists intervened for 72.7% of eligible patients. The most common reasons for lack of

pharmacist intervention during the post-intervention period included anticipating discontinuation of

therapy within 24 hours and initiation of therapy during non-clinical hours.

CONCLUSION: There was a high rate of pharmacist participation in the post-intervention period. In

addition, although underpowered, there was a trend towards improved serum trough and AUC/MIC

target attainment. The degree of pharmacist influence on vancomycin management during the pre-

intervention period is unknown, which limits evaluation of the true impact of this intervention.

Introduction

After more than 50 years of clinical use, vancomycin remains one of the most widely used

antibiotics for treatment of serious gram-positive infections1. It is considered bactericidal against

Staphylococcus and Streptococcus and bacteriostatic against Enterococcus. Traditionally, serum trough

concentrations have been used to monitor vancomycin efficacy and toxicity. Although data from

experimental and clinical studies have demonstrated that the area under the curve (AUC) to minimum

inhibitory concentration (MIC) ratio (AUC/MIC) is the best parameter to predict the effectiveness of

vancomycin, obtaining multiple serum levels in a clinical setting can be difficult2,3.

Vancomycin dosing regimens that reach an AUC/MIC ratio of ≥ 400 have been associated with

an improved clinical and bacteriological response, including more rapid bacterial eradication and

reduced mortality2,4. For MIC ≤ 1mg/L, trough levels of 15-20 mg/L are considered a surrogate marker of

AUC/MIC ≥ 4005. Guidelines have recommended a dosing regimen of 15-20 mg/kg administered every 8-

12 hours for most patients with normal renal function to achieve the suggested serum concentrations3.

Numerous studies have demonstrated the benefits of pharmacist-directed vancomycin dosing

and monitoring programs6-8. Pharmacist intervention has been shown to improve the number of

patients receiving appropriate vancomycin dosing, the number of appropriately drawn serum trough

concentrations, and trough target attainment. It has also been shown to reduce the incidence of

nephrotoxicity, and optimize the duration of vancomycin therapy. Therefore, the implementation of

such a program can lead to improved clinical outcomes and hospital cost-savings.

Within our community hospital health system, vancomycin dosing is predominately physician-

driven. However, initial dosing regimens often fail to account for important pharmacokinetic factors

such as weight, age, and renal clearance. As a result, vancomycin concentrations may fall well below the

targeted therapeutic window. The objective of this study is to evaluate the impact and feasibility of

implementing a pharmacist-directed vancomycin dosing and monitoring program within our institution.

Methods

Study Design

This was a pre-post intervention study conducted at an 870-bed, acute care community health

system. Target attainment was assessed through a retrospective analysis of all patients who received

vancomycin between August 12, 2017 and February 12, 2018 (“pre-intervention group”). All patients

who received vancomycin and pharmacist intervention between February 26, 2018 and May 25, 2018

were prospectively evaluated (“post-intervention group”).

Patient Population

Inpatients 18 years or older were eligible for inclusion if they were receiving intravenous

vancomycin therapy with a trough drawn at steady state, defined as 30 minutes prior to the 4th or

subsequent dose. Patients receiving dialysis or intermittent vancomycin dosing based on serum trough

levels were excluded.

Intervention

The implemented intervention was pharmacist assessment and recommendation to adjust

vancomycin dosing regimens within 24 hours of initiation. A standardized institutional vancomycin

therapeutic drug monitoring guideline was developed prior to February 2018 to guide pharmacist

interventions (Appendix I). Deviations from the guideline were permitted based on pharmacist clinical

judgement. In order to maximize interventions for patients initiated on vancomcyin, education on

guideline-based recommendations was provided to all pharmacists before the post-intervention period.

Outcomes

The primary outcome was the rate of trough target attainment defined as 10-15 mg/L (± 0.5

mg/L) for urinary tract infections and simple cellulitis, and 15-20 mg/L (± 0.5 mg/L) for serious

infections3. Secondary outcomes included rate of AUC/MIC target attainment of ≥ 400 for all S.aureus

infections and incidence of nephrotoxicity, defined as an increase in serum creatinine (SCr) by 45 µmol

or 50%, whichever was greater, on at least 2 consecutive days during receipt of vancomycin. AUC/MIC

ratios were calculated using a previously validated equation9. Feasibility was assessed by measuring rate

of pharmacist interventions and identifying barriers to implementation.

Data Collection

Pre-intervention patients meeting study eligibility criteria were identified via electronic medical

records. Data on patient demographics, vancomycin dosing regimen, and indication for therapy were

collected using a paper based tool (Appendix II). Post-intervention patients meeting study eligibility

criteria were identified by clinical pharmacists responsible for their care. Pharmacists documented

interventions on a paper-based or electronic standardized documentation tool (Appendix III).

Statistical Analysis

It was determined that 85 patients per treatment group would yield an 80% power to detect a

21% relative difference in the percentage of patients who achieved target trough based on previous

studies7. Categorical and continuous data were compared using the Chi-squared test and Mann-Whitney

U test or Independent Sample’s T test, respectively. All p values were 2-tailed and statistically significant

at α ≤ 0.05.

Results

Baseline Characteristics

A total of 1044 patients were evaluated for inclusion in the analysis, with 85 and 40 patients

enrolled in the pre- and post-intervention groups, respectively (Figure 1). There were no statistically

significant differences in baseline characteristics between groups (Table 1). Seventy one (83.5%) and 39

(97.5%) patients in the pre- and post-intervention groups, respectively, had a target trough of 15-20

mg/L at initiation of therapy. The most common sources of infection were respiratory (18.8%) and bone

and joint infections (18.8%) in the pre-intervention group and bacteremia (25.0%) in the post-

intervention group.

Primary Outcome

Rates of trough target attainment in the pre- and post-intervention groups are displayed in

Figure 2 and Table 2. Pharmacist intervention within 24 hours of vancomycin initiation resulted in trough

target attainment in 13 (32.5%) patients, compared to 21 (24.7%) in the pre-intervention group

(p=0.361) (Figure 2).

Secondary Outcomes

Rates of AUC/MIC target attainment in the pre- and post-intervention groups are displayed in

Figure 3 and Table 2. For S. aureus infections, pharmacist intervention resulted in AUC/MIC target

attainment in 8 (88.9%) patients, compared to 13 (76.5%) in the pre-intervention group (p=0.628)

(Figure 2). In the pre-intervention group, the respective percentage of S.aureus vancomycin MIC

<0.5mg/L, 1mg/L, and 2mg/L were 3 (17.6%), 14 (82.4%) and 0 (0.0%). In the post-intervention group,

respective MICs were 5 (55.6%), 4 (44.4%) and 0 (0.0%). Two patients developed nephrotoxicity during

the enrollment period; both were in the post-intervention group (Table 2). Nephrotoxicity, determined

based on physician documentation, was attributed to the initiation of furosemide and sulfamethoxazole-

trimethoprim, respectively. There was insufficient data to assess nephrotoxicity in 5 (12.5%) post-

intervention patients, compared to 21 (24.7%) pre-intervention patients.

Of the 55 patients who met eligibility criteria, 40 (72.7%) patients successfully received

pharmacist intervention. Of the remaining 15 eligible patients, pharmacists were unable to intervene on

8 (14.5%) patients and 7 (12.7%) patients lacked pharmacist documentation (Table 3). The most

commonly cited reasons for lack of intervention included anticipation of discontinuation of therapy

within 24 hours and initiation of therapy during non-clinical hours.

Discussion

A consensus review on vancomycin monitoring by the American Society of Health-System

Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases

Pharmacists states that the AUC/MIC ratio is the best pharmacodynamic parameter to predict clinical

effectiveness3. However, due to the practical limitations of obtaining multiple serum concentrations,

guidelines have advocated for the use of serum trough concentrations of 15-20 mg/L as a surrogate

marker for AUC/MIC ≥ 400 when MIC ≤ 1mg/L for complicated infections caused by S. aureus3. Dosing

regimens of 15-20 mg/kg administered every 8-12 hours are recommended for most patients with

normal renal function to achieve this serum trough target3.

Numerous studies have demonstrated that pharmacist-directed vancomycin dosing and

monitoring programs improve the number of patients receiving appropriate dosing and the number of

appropriately drawn serum trough concentrations6-8. However, many of these studies only assessed

concordance with guideline dosing recommendations and dosing nomograms based on population

pharmacokinetics. Our study differs from the aforementioned in that we assessed trough target

attainment. Our results suggest a trend towards improved trough target and AUC/MIC target attainment

with pharmacist intervention within 24 hours of vancomycin initiation. Although the improved AUC/MIC

target attainment in the post-intervention group may have been confounded by a higher proportion of

S.aureus with MICs of 1mg/L in the pre-intervention group, trough target attainment remained higher in

the post-intervention group (29.4% vs. 33.3%, p = 0.243)

Although vancomycin is often cited to cause nephrotoxicity and ototoxicty, their actual

incidence has decreased with improvements to the vancomycin purification process11. The

nephrotoxicity that occurred in the two post-intervention patients was attributed to the initiation of

concurrent nephrotoxic agents. This is in keeping with the literature, where most reported vancomycin

toxicities involve the use of concomitant nephrotoxic agents or co-morbidities that predispose patients

to nephrotoxicity. There was more serum creatinine (SCr) monitoring in the post-intervention group,

which suggests that heightened monitoring by pharmacists may have increased the detection of

nephrotoxicity.

The feasibility of implementing a pharmacist-directed dosing and monitoring program has not

been previously reported in literature. At the William Osler Health System, pharmacy services are

available at all hours, but clinical services are only available on weekdays between 0800h and 1600h.

The largest barriers to program implementation include anticipation of therapy discontinuation within

24 hours and initiation during non-clinical hours. Therefore, improving participation of dispensary

pharmacists in vancomycin dosing during non-clinical hours may improve trough target attainment and

decrease rates of nephrotoxicity.

Limitations

Our study has several important limitations. It was underpowered to detect a statistically

significant difference in trough target attainment between the two groups. In addition, the degree of

pharmacist involvement in vancomycin management during the pre-intervention period is unknown,

which limits evaluation of the true impact of the intervention.

At our institution, it is not a standard of practice to collect two serum concentrations within the

same dose, which is necessary to directly measure AUC. Therefore, instead of calculating patient-specific

vancomycin clearance, AUC was estimated using a validated vancomycin clearance equation9 based on

population pharmacokinetics. One limitation to this equation is that it assumes a one-compartment

model, whereas numerous pharmacokinetic studies have proven that vancomycin is eliminated through

a two- to three compartment model which overestimates vancomycin clearance in certain situations

such as unstable renal function13. Although, Bayesian estimation procedures have been advocated as a

more accurate estimation of vancomycin AUC, this technique requires patient-specific variables that

were not always readily available due to the retrospective nature of this study.

Finally, the vancomycin MIC for S. aureus can differ depending on the testing method used.

Although some literature suggests that VITEK-2 is more likely to undercall the vancomycin MIC, the

clinical significance of this (ie. Reduced vancomycin efficacy) is unknown14. The target AUC/MIC ratio of

≥400 was first validated using results determined via broth microdilution (BMD)2 and may not be

applicable to MICs determined using VITEK-2.

Conclusion

There appears to be a trend towards improved vancomycin trough and AUC/MIC target

attainment with pharmacist intervention within 24 hours of therapy initiation. Therefore,

implementation of a pharmacist-directed therapeutic drug monitoring program may result in improved

trough target attainment, reduced physician workload, expansion of pharmacist involvement in patient

care, and improved safety monitoring. Target attainment may be increased by improving pharmacist

intervention during non-clinical hours.

References

1. Moellering RC Jr. Vancomycin: a 50-year reassessment. Clin Infect Dis. 2006;42(sup 1):S3-4

2. Moise-Broder PA, Forrest A, Birmingham MC et al. Pharmacodynamics of vancomycin and other

antimicrobials with Staphylcoccus aureus lower respiratory tract infections. Clin Pharmacokinet

2004; 43(13): 925-942

3. Rybak M, Lomaestro B, Rotschafer JC et al. Therapeutic monitoring of vancomycin in adult

patients: a consensus review of the American Society of Health-System Pharmacists, the

Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J

Health Syst Pharm. 2009;66:82-98

4. Holmes NE, Turnidge JD, Munckhol WJ et al. Vancomycin AUC/MIC ratio and 30-day mortality in

patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother.

2013;57(4):1654-1663

5. Patel N, Pai MP, Rodvold KA et al. Vancomycin: We can’t get there from here. Clin Infect Dis

2011:52(8): 969-74

6. Marquis K, DeGrado J, Labonville S et al. Evaluation of a pharmacist-directed vancomycin dosing

and monitoring pilot program at a tertiary academic medical center. Ann Pharmacother.

2015;49(9):1009-14

7. Han Z, Pettit N, Landon E et al. Impact of pharmacy practice model expansion on

pharmacokinetic services: optimization of vancomycin dosing and improved patient safety. Hosp

Pharm. 2017 Apr;52(4):273-279

8. Taghvaye H, Khataminia M, Hadjibabaie M. PS-035 evaluation of pharmacist intervention on

vancomycin dosing and nephrotoxicity prevention. European Journal of Hospital Pharmacists

2017;24: Suppl 1

9. Rodvold K, Blum R, Fischer J et al. Vancomycin pharmacokinetics in patients with various

degrees of renal function. Antimicob Agents Chemother 1988; 32(6):848-52

10. Hale C, Seabury R, Steele J et al. Are vancomycin trough concentrations of 15 to 20 mg/L

associated with increased attainment of AUC/MIC ≥ 400 in patients with presumed MRSA

infection? J Pharm Pract. 2017;30(3):329-335

11. Darko W, Medicis J, Smith A et al. Mississippi mud no more: cost-effectiveness of

pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity.

Pharmacotherapy. 2003;23:643-650

12. Jeffres M, Isakow W, Doherty J et al. A retrospective analysis of possible renal toxicity associated

with vancomycin in patients with health care–associated methicillin-resistant Staphylococcus

aureus pneumonia. Clin Ther. 2007;29:1107-1115

13. Avent M, Vaska V, Rogers B et al. Vancomycin therapeutics and monitoring: a contemporary

approach. Intern Med J. 2013;43:110-119

14. Rybak M, Vidaillac C, Sader H et al. Evaluation of vancomycin susceptibility testing for

methicillin-resistant Staphylococcus aureus: comparison etest and three automated testing

methods. J Clin Microbiol. 2013;7:2077-81

Appendix I: Vancomycin Dosing and Monitoring Guidelines for Adults

Vancomycin Dosing and Monitoring Guidelines for Adults Please use the following guideline for all patients over the age of 18 initiated on vancomycin therapy between February 1, 2018 and April 30, 2018. Pharmacists may choose to deviate from these guidelines based on clinical judgment.

EXCLUSION CRITERIA

Patients on hemodialysis

Patients receiving intermittent vancomycin dosing based on serum trough concentrations

If your patients meets any of the exclusion criteria, please refer to alternate drug information resources

EMPIRIC DOSING

A. Loading Dose: A loading dose can be used to facilitate rapid attainment of trough serum vancomycin concentration in patients with complicated infections (ie. bacteremia, endocarditis, osteomyelitis, complicated skin and soft tissue infections, meningitis, and hospital acquired pneumonia)

Recommended loading dose: 25-30mg/kg (based on actual body weight)

B. Maintenance Dosing: i) Dose: 15mg/kg (based on actual body weight) ii) Choose dosing interval based on chart below

SCr (µmol/L)

Age (years)

Below 40 40-49 50-59 60-69 70 and Older

40-60 Q8H

Q8H Q8H Q8-12H Q12H

61-80 Q8-12H Q12H

Q12H

81-100 Q12H

Q12H

Q12-24H Q12-24H 101-120

Q12-24H

Q12-24H 121-140 Q12-24H

141-160

161-180 Q24H Q24H Q24H

Above 180 Consider Intermittent Dosing

THERAPEUTIC DRUG MONITORING Data do not support using peak serum vancomycin concentrations

Trough monitoring is recommended for all patients

Serum trough concentrations should be obtained 30 minutes prior to next dose at steady state conditions (4th or subsequent dose). Do not include loading dose, if given.

Indication Target Trough (mg/L)

Uncomplicated cellulitis, UTI 10-15

Complicated infections (ie. bacteremia, endocarditis, osteomyelitis, complicated skin and soft tissue infections, meningitis, and hospital acquired pneumonia)

15-20

DOSE ADJUSTMENTS

Measured Trough (mg/L) Recommended Dosage Adjustments

Below 10 If patient on Q24H, change interval to Q12H If patient on Q12H, consider changing interval to Q8H or increasing dose

10 – 15 No change if cellulitis or UTI. Consider shortening interval or increasing dose if complicated infection

15 – 20 No change if complicated infection. Consider prolonging interval or decreasing dose if cellulitis or UTI

Above 20

Consider prolonging interval or decreasing dose *May need to hold dose or consider intermittent based dosing for significantly elevated troughs. Consult antimicrobial stewardship pharmacist, if necessary.

Appendix II: Data Collection Tool for the Pre-Intervention Group

Data Collection Tool for New Start Vancomycin EXCLUSION CRITERIA:

Patients on hemodialysis

Patients receiving intermittent vancomycin dosing based on serum trough concentrations If your patients meets any of the exclusion criteria, please do not continue

A. Patient Information

Patient MRN: Age: Sex: M / F Height: Weight:

SCr (at initiation of vancomycin therapy): CrCl (calculated using the Cockcroft Gault Equation:

B. Indication for Vancomycin Therapy

Indication for Vancomycin Therapy

Empiric therapy

Documented infection

Target Trough Concentration:

10mg/L – 14.9mg/L

15mg/L – 20mg/L

C. Vancomycin Dosing Regimen and Laboratory Values

Date (MM/DD)

Time (0000h)

Dose (mg)

Frequency (hours)

Time of Trough (0000h)

Trough (mg/L)

SCr (µmol/L)

Was the trough appropriately drawn (30min prior to the 4th or subsequent dose)?

Yes

No

D. Adverse Events

Nephrotoxicity:

Yes, date: ____________________________

No

*Nephrotoxicity is defined as an increase in SCr by 45µmol/L or 50% from baseline, whichever is greater, on at least 2 consecutive days during period vancomycin therapy.

Appendix III: Pharmacist Documentation Tool for the Post-Intervention Group

Pharmacist Documentation Tool for New Start Vancomycin Please provide the following information for all patients over the age of 18 initiated on vancomycin therapy between February 1, 2018 and April 30, 2018.

EXCLUSION CRITERIA: Patients on hemodialysis

Patients receiving intermittent vancomycin dosing based on serum trough concentrations

1. Does the patient meet the eligibility criteria?

Yes

No If your patients meets any of the exclusion criteria, please do not continue

PHARMACIST NAME: ____________________________________________________________ PATIENT DEMOGRAPHICS:

Patient MRN: Patient Name: Age: Sex: M / F

Height: Weight: SCr (at initiation of vancomycin therapy): CrCl (calculated using the Cockcroft Gault Equation):

VANCOMYCIN THERAPY:

1. What is the indication for vancomycin therapy

Empiric Management

Documented Infection 2. What is the target trough concentration at initiation vancomycin therapy?

10mg/L to 14.9mg/L

15mg/L to 20mg/L 3. What is the initial (prescriber initiated) dosing regimen?

Dose Frequency 500mg

750mg

Q6H

Q8H

1,000mg Q12H

1,250mg Q24H

1,500mg

1,750mg

2,000mg

Pharmacist Assessment/Intervention within First 24 Hours of Administration: Pharmacist assessment consists of clinical pharmacist verification of the dosing regimen to ensure appropriateness based on patient factors including, but not limited to, age, weight, indication and renal function. Pharmacist intervention includes optimization of dosing when warranted.

4. Was an assessment/intervention made WITHIN the first 24 hours of therapy initiation?

Yes

Dosage regimen was appropriate, no change was made

Dosage regimen was inappropriate, an intervention was made. New dosing regimen is:

Dose Frequency 500mg

750mg

Q6H

Q8H

1,000mg Q12H

1,250mg Q24H

1,500mg

1,750mg

2,000mg

No Please provide a reason for why no assessments/interventions were made (check all that apply):

Dosing regimen was inappropriate, a recommendation for dosage adjustment was attempted but rejected by prescriber

Pharmacist discomfort with vancomycin dose adjustments

Workload

Time constraints

Other:

ONGOING MONITORING:

5. Was the initial trough concentration drawn appropriately (30min prior to the 4th of subsequent

dose)?

Yes No

6. If yes, what is the initial steady state serum trough concentration?

Below 5mg/L

5mg/L to 9.9mg/L

10mg/L to 14.9mg/L

15mg/L to 20mg/L

Above 20mg/L

7. Did your patient experience nephrotoxicity* associated with vancomycin therapy?

Yes No

*Nephrotoxicity is defined as an increase in SCr by 45µmol/L or 50% from baseline, whichever is greater, on at least 2 consecutive days during period vancomycin therapy.

Free Text

Appendix IV: Tables and Figures Figure 1: Patient enrollment

15 Feasibility

725 Inpatients Received

IV Vancomycin

319 Inpatients Received

IV Vancomycin

85 Enrolled

395 No Trough 37 Inappropriate Trough 35 Age < 18 years old 96 Dialysis 27 Dose by Trough

186 No Trough 32 Inappropriate Trough 9 Age < 18 years old 28 Dialysis 9 Dose by Trough

55 Eligible

40 Enrolled

Pre-Intervention Post-Intervention

Table 1. Baseline Demographics

Characteristic Pre-Intervention (n=85) Post-Intervention (n=40)

Age, years, median (IQR) 64 (50-77) 66 (51-85)

Female sex 31 (36.5) 20 (50.0)

Weight, kg, median (IQR) 71.5 (60.0-87.1) 68.2 (60.9-81.7)

Target Trough Concentration

10-15mg/L 14 (16.5) 1 (2.5)

15-20mg/L 71 (83.5) 39 (97.5)

Indication

Empiric 48 (56.5) 24 (60.0)

Documented 37 (43.5) 16 (40.0)

Type of Infection

Meningitis 9 (10.6) 4 (10.0)

Endocarditis 0 (0.0) 2 (5.0)

Bacteremia 11 (12.9) 10 (25.0)

Respiratory 16 (18.8) 4 (10.0)

Gastrointestinal 2 (2.4) 3 (7.5)

Urinary 12 (14.1) 5 (12.5)

Ocular 0 (0.0) 1 (2.5)

Skin and Soft Tissue 10 (11.8) 9 (22.5)

Bone and Joint 16 (18.8) 2 (5.0)

Febrile Neutropenia 8 (9.4) 0 (0.0)

Fever of Unknown

Origin 1 (1.2) 0 (0.0)

Baseline SCr, µmol/L,

median (IQR) 70 (56.5-83.0) 73 (56.5-104.0)

Data are expressed as n (%), unless otherwise specified IQR: Interquartile range SCr: Serum creatinine

Figure 2. Trough target attainment in the pre- and post-intervention groups.

Figure 3. AUC/MIC target attainment in the pre- and post-intervention groups for S.aureus isolates.

24.7

32.5

0

5

10

15

20

25

30

35

Pre-Intervention Post-Intervention

Tro

ugh

Tar

get

Att

ain

men

t (%

)

76.5

88.9

0

10

20

30

40

50

60

70

80

90

100

Pre-Intervention Post-Intervention

AU

C/M

IC T

arge

t A

ttai

nm

ent

(%)

Table 2. Outcomes

Result Pre-Intervention (n=85) Post-Intervention (n=40) p-value

Primary Outcomes

Trough Target Attainment 21 (24.7) 13 (32.5) 0.361

Secondary Outcomes

AUC/MIC Target Attainment* 13 (76.5) 8 (88.9) 0.628

Nephrotoxicity 0 (0) 2 (5)† 0.095

Rate of Pharmacist Intervention (%)‡ N/A 72.7 N/A

Data are expressed as n (%), unless otherwise specified N/A: Not applicable *AUC/MIC attainment calculated for 17 and 9 patients in the pre-intervention and post-intervention groups, respectively †Nephrotoxicity attributed to initiation of other nephrotoxic agents ‡Calculated from 55 eligible patients

Table 3. Feasibility

Reasons for Lack of Intervention Post-Intervention (n=8)

Recommendation rejected by prescriber 3 (37.5)

Pharmacist discomfort with vancomycin dose adjustments 0 (0.0)

Workload 0 (0.0)

Time Constraints 0 (0.0)

Other: Initiation during non-clinical hours

5 (62.5)

Appendix V: Calculations and Definitions

Vancomycin AUC was calculated using the total daily dose of the initial vancomycin dosing

regimen based on the following formula9:

AUC =total daily dose (mg)

(CrCl x 0.79 + 15.4)x 0.06

Creatinine clearance (CrCl) was estimated using the Cockcroft-Gault equation, using the most

recently measured SCr. For patients 130% above their ideal body weight (IBW), an adjusted body weight

(ABW) was used10. ABW was calculated based on the following formula:

ABW = IBW + 0.4[actual body weight (kg) – IBW]

Actual body weight was used in all dosing calculations3.

MIC was determined by VITEK-2, the standard at our institution.