/clinical/,/clinical/cckm-tools/,/clinical/cckm-tools/content/,/clinical/cckm-tools/content/cpg/,/clinical/cckm-tools/content/cpg/infection-and-isolation/,

/clinical/cckm-tools/content/cpg/infection-and-isolation/name-97549-en.cckm

20180119

page

100

UWHC,UWMF,

Tools,

Clinical Hub,UW Health Clinical Tool Search,UW Health Clinical Tool Search,Clinical Practice Guidelines,Infection and Isolation

Intravenous Vancomycin Use – Adult – Inpatient

Intravenous Vancomycin Use – Adult – Inpatient - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Infection and Isolation


1
Intravenous Vancomycin Use – Adult –
Inpatient Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ...................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS AND ABBREVIATIONS ..................................................................................... 5
INTRODUCTION ....................................................................................................................... 7
RECOMMENDATIONS .............................................................................................................. 7
TABLE 1. EMPIRIC INTERMITTENT VANCOMYCIN DOSING NOMOGRAM ........................10
TABLE 2. VANCOMYCIN TARGET PHARMACODYNAMIC PARAMETERS ........................13
TABLE 3. CONTINUOUS INFUSION VANCOMYCIN DOSING ..............................................15
TABLE 4. ADJUSTMENTS FOR CONTINUOUS VANCOMYCIN INFUSIONS WITH
VANCOMYCIN PLATEAUS ABOVE 30 MCG/ML ....................................................................16
UW HEALTH IMPLEMENTATION ............................................................................................16
APPENDIX A. VANCOMYCIN GUIDELINE FLOW CHART .....................................................17
APPENDIX B. VANCOMYCIN PHARMACOKINETIC EQUATIONS83 .....................................18
APPENDIX C. CHARACTERIZATION OF VANCOMYCIN MICS AGAINST
STAPHYLOCOCCUS AUREUS ...............................................................................................19
REFERENCES .........................................................................................................................20
Contact for Changes:
Name: Philip J Trapskin, PharmD, BCPS
Phone Number: 608-263-1328
Email Address: PTrapskin@uwhealth.org
Contact for Content:
Name: Lucas Schulz, PharmD, BCPS AQ-ID
Phone Number: 608-890-8617
Email Address: lschulz2@uwhealth.org
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 09/2016CCKM@uwhealth.org


2
Guideline Authors:
Ronald E. Kendall, PharmD; Lucas T Schulz PharmD, BCPS AQ-ID; Marie H.
Pietruszka, PharmD, BCPS, AAHIVP, CNSC

Coordinating Team Members:
Joshua Vanderloo, PharmD, Drug Policy Program

Review Individuals/Bodies:
Alex Lepak, MD; Barry Fox, MD; David Andes, MD; Jeff Fish, PharmD, BCPS; Philip
Trapskin, PharmD, BCPS; Mei Jorgenson, PharmD, BCPS; Jill Strayer, PharmD,
BCPS; Teresa Darcy, MD
Richard Cornwell, MD; Trina Hollatz, MD

Committee Approvals/Dates:
Laboratory Practice Committee May 2015
Antimicrobial Use Subcommittee June 2015; August 2016
UW Health Pharmacy and Therapeutics Committee (Last Periodic Review: July 2015)
ξ Interim revisions: September 2016

Release Date: September 2016

Next Review Date: July 2017

Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


3
Executive Summary
Guideline Overview
This guideline describes the optimal use of intravenous vancomycin.

Key Revisions (Interim revisions 9/2016)
1. Addition of vancomycin use guidelines for cystic fibrosis (CF) patients.

Key Practice Recommendations
Vancomycin is used for empiric and definitive therapy of suspected and documented Gram-positive
infections such as those involving methicillin-resistant Staphylococcus aureus (MRSA) and beta-lactam-
resistant Streptococcus and Enterococcus species. Optimal use of vancomycin is of great importance
among hospitalized patients due to the high morbidity and mortality associated with infections caused by
these organisms. Optimization of vancomycin dosing and monitoring is paramount in order to maximize
efficacy and minimize toxicity. Evaluating the clinical necessity for vancomycin use is equally as
important in order to curtail inappropriate utilization which is associated with increased adverse effects,
the development of vancomycin-resistant bacteria, and increased costs and use of healthcare
resources.1,2
1. Clinical investigation to evaluate the necessity for vancomycin use in acute bacterial skin and skin
structure infections, diabetic foot infections, intraabdominal infections, and pneumonia should be
pursued in accordance with the tools and recommendations in Section 1.3-6
2. The dosing of vancomycin for included patient populations should be based upon
recommendations outlined in Table 1. In general, weight-based loading doses are utilized
followed by maintenance dosing based on weight, renal function, and indication.
3. Monitoring of vancomycin therapy should include:1
ξ Continual assessment of the need for vancomycin and the ability to discontinue therapy based
on the results of diagnostic testing and clinical assessment of the patient
ξ Therapeutic drug monitoring in certain scenarios as described in Section 3.3.
ξ Monitoring renal function and performing dose adjustments for renal dysfunction
ξ Minimizing the use of concomitant nephrotoxins as feasible
ξ Assessing for other rare adverse effects such as serious systemic and dermatological
reactions, ototoxicity, and hematological toxicity
4. When therapeutic drug monitoring is indicated it may occur via two different strategies: trough-
based monitoring and AUC24/MIC-based monitoring.1,7-20
a. Refer to Section 4.0 for guidance on which method is most appropriate.
b. Pharmacodynamic targets are based on indication and outlined in Table 2.
c. When not at target concentrations, vancomycin doses and/or dosing interval should be
adjusted in a proportional fashion due to the linear pharmacokinetics of vancomycin.
5. Vancomycin may be administered to patients receiving renal replacement therapy. Dosing and
therapeutic drug monitoring require special considerations in this population as outlined in
Section 5 for both intermittent hemodialysis and continuous renal replacement therapy.
6. Vancomycin administration can beneficial via continuous infusion in documented or highly
suspected Gram-positive organism ventriculoperitoneal shunt or meningeal infections. Dosing for
this is outlined in Table 3, and dose adjustments based on drug concentrations are outlined in
Table 4.


Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


4
Companion Documents
ξ Diagnosis and Treatment of Skin, Skin Structure, and Soft Tissue Infections – Adult –
Inpatient – Clinical Practice Guideline
ξ Diagnosis and Treatment of Infections of the Urinary Tract - Adult - Inpatient/Ambulatory
ξ Renal Function-Based Dose Adjustments – Adult – Inpatient – Clinical Practice
Guideline
ξ Continuous Renal Replacement Therapy Based Dose Adjustments – Adult – Inpatient –
Clinical Practice Guideline
ξ Surgical and Interventional Radiology Antimicrobial Prophylaxis – Adult/Pediatric –
Inpatient – Clinical Practice Guideline
ξ Clinical Monitoring of Outpatient Parenteral Antimicrobial Therapy (OPAT) – Adult –
Inpatient/Ambulatory
ξ Prevention, Diagnosis and Treatment, and of Clostridium difficile Infection – Adult –
Inpatient – Clinical Practice Guideline

Scope
Clinical Specialty:
This guideline may be used by any clinician treating a patient with intravenous vancomycin.

Intended Users:
Physicians, Advanced Practice Providers, Pharmacists, and Nurses.

Objective:
The objective of this guideline is to improve the use of vancomycin by optimizing the evaluation of the
clinical necessity for vancomycin therapy, dosing of vancomycin dosing based on pharmacodynamic and
pharmacokinetic principles and parameters, and the monitoring of vancomycin, including therapeutic drug
monitoring.

Target Population:
All adult patients requiring antimicrobial therapy with intravenous vancomycin should receive therapy in
accordance with these guidelines with the following exclusions:
a. Patients under the age of 18 years are excluded from this guideline. These patients may receive
care in accordance with these guidelines at the discretion of the pediatric primary team.
b. Intravenous vancomycin use for surgical prophylaxis is excluded from this guideline and can be
found in the Surgical and Interventional Radiology Antimicrobial Prophylaxis – Adult/Pediatric –
Inpatient – Clinical Practice Guideline.
ξ Oral vancomycin use for the Treatment of Clostridium difficile infection is excluded from this
guideline and may be found in the Prevention, Diagnosis and Treatment, and of Clostridium
difficile Infection – Adults – Inpatient – Clinical Practice Guideline
c.

Interventions and Practices Considered:
ξ Proper determination of a drug-resistant Gram positive infection
ξ Vancomycin dosing (intermittent, continuous, renal replacement therapy)
ξ Vancomycin monitoring and therapeutic drug concentration monitoring

Major Outcomes Considered:
Successful management of patients treated with vancomycin including: clinical cure rate, microbiological
cure rate, achievement of target pharmacokinetic and pharmacodynamic parameters, incidence of acute
kidney injury, and mitigation of the development of vancomycin resistant bacteria.
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


5

Guideline Metrics:
Successful management of patients treated with vancomycin including: clinical cure rate, microbiological
cure rate, achievement of target pharmacokinetic and pharmacodynamic parameters, incidence of acute
kidney injury, and mitigation of the development of vancomycin resistant bacteria.
Methodology
Methods Used to Collect/Select the Evidence:
A review of PubMed database and Google Scholar was conducted with combinations of the keywords:
vancomycin and treatment, Gram positive infection, de-escalation, resistance, adverse effects,
monitoring, therapeutic drug monitoring, dosing, pharmacokinetics, pharmacodynamics, administration,
hemodialysis, continuous renal replacement therapy, or special populations. References from the articles
were also searched. Finally, the personal libraries of the authors were queried.

Methods Used to Assess the Quality and Strength of the Evidence:
Review of the literature and weighing according to the rating scheme (see below).

Rating Scheme for the Strength of the Evidence and
Recommendations:
A modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology was used to assess
the Quality and Strength of the Evidence in this Clinical Practice Guideline.21

Definitions and Abbreviations
1. Total body weight (TBW) is defined as the actual total mass of the patient in kilograms.
2. Body mass index is defined by the following equation:22
a. BMI = TBW/(height(m))2
3. Ideal body weight (IBW) is defined by the following equations.23
a. Males IBW = 50 kg + 2.3 kg for each inch over 5 feet in height.
b. Females IBW = 45.5 kg + 2.3 kg for each inch over 5 feet in height.
4. Adjusted body weight (AdjBW) is defined by the following equation:24
a. AdjBW = IBW + (0.4 x (TBW – IBW)
5. Lean body weight is defined by the following equations:24
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


6
a. Males LBW = (9270 x TBW)/(6680 + 216 x BMI)
b. Females LBW = (9270 x TBW)/(8780 + 244 x BMI)
6. Class I obesity is defined as a BMI (kg/m2) in the range of 30.00-34.99.25
7. Class II obesity is defined as a BMI (kg/m2) in the range of 35.00-39.99.25
8. Class III obesity is defined as a BMI (kg/m2) greater than or equal to 40.25
9. Cockcroft-Gault: CLCR Male = (IBW x [140 - Age]) / (SCr x 72)
a. CLCR Female = 85% of male value
b. Weight is measured in kilograms.26
10. ABW: Actual Body Weight
11. AUC: Area under the curve
12. HCAP: Healthcare-associated pneumonia
13. CAP: Community-acquired pneumonia
14. ABSSSI: Acute bacterial skin and skin structure infection
15. MIC: Minimum inhibitory concentration
16. HD: Hemodialysis
17. CRRT: Continuous renal replacement therapy
18. CVVHD: Continuous veno-venous hemodialysis
19. Dry weight:27 The weight of a patient when they are clinically euvolemic
20. SCr: Serum creatinine
21. Empiric therapy:28 Selection of antimicrobials based on clinical presentation prior to culture results
22. Definitive therapy:28 Deescalation of antimicrobial selection to narrower spectrum based on specific
pathogen-directed treatment with culture results or with no culture results after 72 hours
23. Sepsis:29 two or more of the four systemic inflammatory response syndrome criteria (temperature
<36°C or >38°C, heart rate >90/min, respiratory rate >20/min or arterial carbon dioxide pressure
<32 mmHg, white blood cell count <4000/mm3 or >12000/mm3, or ≥10% banded neutrophils) in the
presence of a probable or documented infection
24. Severe sepsis:29 sepsis-induced tissue hypoperfusion or organ dysfunction defined as any of the
following thought to be due to infection: sepsis-induced hypotension, lactate above the upper limit
of normal, urine output <0.5 mL/kg/hr for more than two hours despite adequate fluid resuscitation,
acute lung injury with PaO2/FiO2 <250 in the absence of pneumonia as an infection source, acute
lung injury with PaO2/FiO2 <200 in the presence of pneumonia as an infection source, serum
creatinine >2 mg/dL, bilirubin >2 mg/dL, platelet count <100,000/dL, INR >1.5
25. Septic shock:29 sepsis-induced hypotension persisting despite adequate fluid resuscitation


Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


7
Introduction
Vancomycin has been in clinical use for over 50 years to treat Gram-positive bacterial infections. It was
initially used as a penicillin alternative to treat penicillinase-producing strains of Staphylococcus aureus,
and is now commonly employed against other Gram-positive infections such as those caused by
methicillin-resistant Staphylococcus aureus (MRSA) species and drug-resistant Streptococcus and
Enterococcus species.1 Optimal use of vancomycin is of great importance among hospitalized patients
due to the high morbidity and mortality associated with infections caused by these organisms.2 The
dosing and monitoring of vancomycin need to be optimized to maximize efficacy and minimize toxicity.1
Evaluation of the clinical necessity for vancomycin use is paramount as inappropriate utilization of
vancomycin has the potential to promote the development of resistance to vancomycin.2 Despite the
recent development of antibiotics for Gram-positive infections, vancomycin remains the primary agent in
the treatment of drug-resistant Gram-positive infections.

Recommendations

1. Evaluation of the clinical necessity for vancomycin use in acute bacterial skin and skin
structure infections, diabetic foot infections, intraabdominal infections, and pneumonia.
1.1. Vancomycin is appropriate for the empiric coverage of infections suspected to be caused by
most beta-lactam-resistant Gram-positive bacteria. Appropriate definitive vancomycin therapy
depends upon identification of the infecting organism(s). (Class I, Level A)
1.2. Patients being treated for potential MRSA infection should have diagnostic testing performed to
screen for the presence of MRSA. (Class I, Level C)
1.2.1. Culture results from the suspected site(s) of infection should be used to determine the
need for definitive vancomycin therapy. (Class I, Level C)
1.2.2. For skin and soft tissue infections, MRSA polymerase chain reaction (PCR) swabs can
be beneficial when performed on the nares and pooled groin and axilla. (Class IIa, Level
B) If both are negative, there is a greater than 90% negative predictive value for MRSA
infection and vancomycin discontinuation is reasonable.3,4 (Class IIa, Level B).
1.2.3. For pneumonia, a bronchoalveolar lavage, sputum culture, or MRSA PCR swab of the
nares and throat can be beneficial to screen for the presence of MRSA.5 (Class IIa, Level
C).
1.2.3.1. It is reasonable to discontinue empiric vancomycin in patients without adequate
respiratory cultures who are receiving vancomycin for suspected MRSA
pneumonia but have both nose and throat surveillance cultures negative for
MRSA. (Class IIa, Level B)
1.2.3.2. The combination of a nasal plus a throat culture negative for MRSA has a
negative predictive value of 92 to 100% for MRSA colonization.5,30
1.2.4. For diabetic foot infections, a tissue culture or MRSA PCR swabs performed on the nares
and pooled groin and axilla can be beneficial. The presence of a negative nares swab
has a negative predictive value of 80% for MRSA colonization.6 (Class IIa, Level B). The
presence of a negative nares and pooled groin and axilla swab likely has a negative
predictive value of greater than 80% for MRSA colonization. (Class IIb, Level C)
1.3. Patients being treated for potential drug-resistant Enterococcus species should have diagnostic
testing performed to screen for the presence of drug-resistant Enterococcus species. (Class I,
Level C).
1.3.1. Culture results from suspected site(s) of infection should be used to determine the need
for definitive vancomycin therapy. (Class I, Level C)
1.3.2. In the absence of a positive culture, the benefits of ongoing empiric vancomycin coverage
must be carefully weighed against the risks. (Class I, Level C)
1.4. Once an organism has been isolated that is not resistant to beta-lactams, de-escalation away
from vancomycin and towards a beta-lactam is preferred. (Class I, Level C)


Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


8
2. Empiric Intermittent Vancomycin Dosing
2.1. Intermittent dosing of vancomycin is reasonable for all indications. (Class I, Level B)
2.1.1. It may be reasonable to use continuous infusion vancomycin for confirmed bacterial
meningitis (See Section 6: Continuous Vancomycin Infusion for additional information).1
(Class IIb, Level B)
2.1.2. It is reasonable to dose vancomycin based on total body weight, rounded to the nearest
250 mg increment for ease of preparation. (Class IIb, Level C)
2.1.3. It may be reasonable to cap vancomycin doses at 2000 mg per dose.31,32 (Class IIa,
Level B)
2.1.4. It is reasonable to limit total daily dose of vancomycin to 6000 mg in 24 hours (Class IIa,
Level C)
2.2. It may be reasonable for most patients to receive an initial dose of 25 mg/kg of total body weight,
dose capped at 2000 mg to ensure adequate concentrations are reached sooner as early target
attainment of the area-under-the-curve to minimum inhibitory concentration (AUC24:MIC) ratio is
important for clinical outcomes.1,18,31 (Class IIb, Level C)
2.2.1. Peak vancomycin concentrations alone have never been shown to have a relationship
with either efficacy or toxicity.33
2.2.2. A randomized trial comparing initial vancomycin loading doses versus no loading dose
demonstrated that patients who received loading doses are more likely to have a trough
greater than 15 mcg/mL at a time of 12 hours post-dose. There was no difference in
nephrotoxicity.34
2.2.3. Patients with a Staphylococcus aureus infection exposed to vancomycin concentrations
below 10 mcg/mL may be at risk for therapeutic failure and the potential for the
emergency of vancomycin-intermediate or vancomycin-resistant Staphylococcus aureus.
Therefore it may be reasonable to use vancomycin dosing strategies such as the use of a
loading dose to minimize the time that Staphylococcus aureus is exposed to vancomycin
concentrations below 10 mcg/mL.1,35,36 (Class IIb, Level C)
2.2.4. In patients who are not critically ill and who are receiving vancomycin despite low
likelihood of a drug-resistant Gram positive infection, it may be reasonable to withhold
(i.e. not give) a loading dose and begin therapy with maintenance dosing (See Table 1).
It is expected that the pharmacist make a reasonable effort to discourage vancomycin
use when the risk of vancomycin use may outweigh the benefits.1 (Class IIb, Level C)
2.3. Maintenance dosing of vancomycin should be based on weight, renal function, and desired drug
concentrations. (Class I, Level B)
2.3.1. It is reasonable to estimate creatinine clearance in accordance with the UWHC Renal
Function-Based Dose Adjustments Adult Inpatient Clinical Practice Guideline. (Class IIa,
Level C)
2.3.1.1. The Cockroft-Gault equation is preferred to calculate creatinine clearance in
patients with a BMI between 18.5 and 30 kg/m2.26
[
(140 − 𝑎𝑔𝑒) × 𝐴𝐵𝑊 (𝑘𝑔)
𝑆𝐶𝑟 (
𝑚𝑔
𝑑𝐿 ) × 72
] × (0.85 𝑓𝑜𝑟 𝑓𝑒𝑚𝑎𝑙𝑒𝑠)

2.3.1.2. Obese patients (BMI equal to or 30 kg/m2) have variable amounts of body fat
versus muscle mass making creatinine clearance estimation even more
challenging in this population. No one equation consistently demonstrates
maximal precision or minimal bias.37-40 Either the Salazar-Corcoran equation or
using an adjusted body weight in the Cockcroft-Gault equation will overestimate
creatinine clearance, whereas using ideal body weight will underestimate
clearance. The Salazar-Corcoran equation is more complex and estimates fat
free mass. If a precise estimate of creatinine clearance is required to improve
efficacy or prevent toxicity, then a measured creatinine clearance is
recommended. The equations are:

Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


9
Salazar-Corcoran equation for
men41 [
(137 − 𝑎𝑔𝑒) × [(0.285 x TBW (kg)) + (12.1 × Ht(m)2)]
𝑆𝐶𝑟 (
𝑚𝑔
𝑑𝐿 ) × 51
]
Salazar-Corcoran equation for
men41 [
(146 − 𝑎𝑔𝑒) × [(0.287 x TBW (kg)) + (9.74 × Ht(m)2)]
𝑆𝐶𝑟 (
𝑚𝑔
𝑑𝐿 ) × 60
]
Cockroft-Gault with adjusted body
weight equation38 [
(140 − 𝑎𝑔𝑒) × 𝐴𝑑𝑗𝐵𝑊 (𝑘𝑔)
𝑆𝐶𝑟 (
𝑚𝑔
𝑑𝐿 ) × 72
] × (0.85 𝑓𝑜𝑟 𝑓𝑒𝑚𝑎𝑙𝑒𝑠)

2.3.2. Table 1 describes empiric intermittent vancomycin maintenance dosing for patients with
stable renal function in the absence of any information on steady state trough
concentrations from an ongoing course of therapy.16,42
2.3.2.1. Empiric maintenance dose/frequency adjustments are also reasonable if renal
function changes until a new steady state vancomycin trough is reached.12,43,44
(Class IIa, Level C)
2.3.2.2. It is reasonable for pharmacists to use clinical judgement to deviate from empiric
dosing in Table 1.12,13 (Class IIa, Level B)
2.3.2.3. Renal transplant recipients who are receiving concomitant nephrotoxins such as
calcineurin inhibitors may be candidates for more conservative dosing. (Class
IIb, Level C)
2.3.3. Adult cystic fibrosis patients exhibit vancomycin pharmacokinetics similar to that of
healthy adults.45
2.3.3.1. Empiric dosing regimens (i.e. Table 1) is reasonable for the use of vancomycin
in cystic fibrosis patients.45 (Class IIa, Level B)
2.3.3.2. If available, historical drug monitoring data is probably recommended to guide
empirical dosing in cystic fibrosis patients.46
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


10
Table 1. Empiric Intermittent Vancomycin Dosing Nomogram
Estimated Creatinine
ClearanceA Loading Dose
B,C
Maintenance DoseC
Severe Sepsis and Septic
Shock Non-sepsis Indication
>100 mL/min
25 mg/kg
(maximum 2000 mg)
10-15 mg/kg Q8H 15 mg/kg Q12H or 10 mg/kg Q8HD
80- 99 mL/min 15 mg/kg Q12H 15 mg/kg Q12H
60 -79 mL/min 15 mg/kg Q12H 10 mg/kg Q12H
50-59 mL/min 10 mg/kg Q12H 15 mg/kg Q24H
40-49 mL/min 15 mg/kg Q24H 15 mg/kg Q24H
30-39 mL/min 15 mg/kg Q24H 10 mg/kg Q24H
20-29 mL/min
15 mg/kg Q48H, or monitor
drug concentrations and re-
dose when at target trough
15 mg/kg Q48H
<20 mL/min, not receiving HD Monitor drug concentrations and re-dose when at target
trough
HD 20-25 mg/kg
(maximum 2000 mg) See Section 5
A
This nomogram has not been validated for use in patients with rapidly changing renal function.
B
Information on the decision of whether or not to use a loading dose is contained in Section 2.2. In patients who are not critically ill and who are receiving
vancomycin despite low likelihood of a drug-resistant Gram positive infection, it may be reasonable to withhold (i.e. not give) a loading dose and begin therapy
with maintenance dosing. It is expected that the pharmacist make a reasonable effort to discourage vancomycin use when the risk of vancomycin use may
outweigh the benefits.
C
All loading doses and maintenance doses for intermittent vancomycin is based off of actual body weight and capped at a maximum of 2000 mg per infusion.
D
Clinicians must use clinical judgement to select vancomycin doses in this situation. Initial dosing of 10 mg/kg every 8 hours should only be used in patients
who are younger than 40 years of age, or who are critically ill, or who have severe infections (e.g. ophthalmologic emergencies, periorbital cellulitis, Fournier’s
gangrene, etc.). Renal transplant recipients who are receiving concomitant nephrotoxins such as calcineurin inhibitors may be candidates for more
conservative dosing.
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


11
3. Vancomycin Therapy Monitoring
3.1. Vancomycin therapeutic drug monitoring has been advocated to maintain drug concentrations
within a narrow therapeutic index and to lessen the potential for drug-induced nephrotoxicity and
ototoxicity. Although some debate still occurs about the conflicting evidence regarding the use
of vancomycin concentrations to predict and prevent drug effectiveness or toxicity, vancomycin
therapeutic drug monitoring has been widely adopted.1
3.2. Assessing the potential for deescalation off of vancomycin when beta-lactam susceptible
organisms are isolated should precede any consideration of vancomycin therapeutic drug
monitoring. (Class I, Level C)
3.3. Therapeutic drug monitoring of vancomycin is reasonable for patients in the following scenarios:1
(Level IIa, Class B)
ξ targeting vancomycin concentrations of 15 to 20 mcg/mL
ξ obesity (BMI >30 kg/m2)
ξ high risk for nephrotoxicity (see Section 3.3)
ξ changing urine output/ creatinine or dialysis patients
ξ drug efficacy is questionable (patient not clinically improving)
ξ non-compliance is suspected
ξ concomitant disease states may be altering drug elimination
ξ drug-drug interactions exist
ξ therapy is expected to continue beyond 4 days
3.4. Use of other potential nephrotoxins during vancomycin therapy should be avoided, as feasible,
to prevent nephrotoxicity associated with vancomycin troughs greater than 15 mcg/mL and
increased length of stay and poorer outcomes with vancomycin nephrotoxicity.47 (Class I, Level
B)
3.5. Other risk factors for vancomycin-associated nephrotoxicity should be considered, including:47-51:
(Class I, Level C)
ξ targeting serum concentrations of 15 to 20 mcg/mL or greater
ξ vancomycin AUC24 > 700 mg*hr/L
ξ vancomycin doses > 4000 mg/day
ξ single vancomycin doses > 2000 mg
ξ obesity (BMI >30 kg/m2)
ξ prolonged durations of vancomycin ≥ 2 weeks
ξ history of acute kidney injury
ξ preexisting renal insufficiency
ξ critically ill status
ξ sepsis
ξ concurrent nephrotoxins
3.6. Close monitoring and caution is recommended in cystic fibrosis patients receiving vancomycin
who are at risk for nephrotoxicity, including patients with underlying kidney disease, patients with
a history of AKI, patients who previously received multiple courses of vancomycin,
aminoglycosides and/or colistin, patients in whom vancomycin is used in conjunction with other
nephrotoxic medications (e.g. aminoglycosides, colistin), and patients being treated for an
extended duration (longer than 14 to 21 days).46 (Class I, Level C)
3.7. Alternative treatment regimens and infectious disease advice should be considered and
vancomycin toxicity risk should be weighed against the benefits of continued vancomycin
therapy if a total daily dose of more than 4000 mg, but especially 6000 mg of vancomycin is
required to achieve target trough concentrations. (Class I, Level C)
3.8. Vancomycin-induced histamine-release syndrome occurs in 3.7-47% of infected patients and is
characterized by pruritus, an erythematous rash of the face, neck, and upper torso, dizziness,
agitation, chills, fever, and paraesthesia around the mouth. Severe cases present with chest
pain and dyspnea. Reactions can be immediate or delayed and may occur at any point during
the treatment course with vancomycin. Vancomycin-induced histamine release syndrome is
anaphylactoid, is a non-IgE- mediated reaction, and occurs due to mast call and basophil
degranulation and histamine release.52
3.8.1. For the treatment of vancomycin-induced histamine release syndrome, it is reasonable to
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


12
include: diphenhydramine 50 mg IV or PO (with or without H2 receptor antagonist (e.g.
ranitidine)) and the vancomycin infusion can reasonably be held.52 (Level IIa, Class C).
3.8.1.1. True anaphylaxis, while very rare, is possible and must be ruled out.
Hypotension requiring intravenous fluids and vasopressors is also rare.52
3.8.1.2. There is no established role for steroids in the treatment of vancomycin-
induced histamine release syndrome.52
3.8.1.3. When the reaction dissipates, it is reasonable to resume vancomycin at a
slower infusion rate.52,53 (Level IIa, Class C).
3.8.1.3.1. Antihistamine pre-medication can be beneficial as a pretreatment
to prevent future symptoms of vancomycin-induced histamine
release syndrome.54 (Level IIa, Class B)
3.8.1.3.2. Vancomycin-induced histamine release syndrome is not
considered an allergy and should not preclude use of future
vancomycin with premedication and slower infusion times.52,53
(Level IIa, Class C)
3.8.2. Vancomycin should be administered at a rate less than or equal to the maximum infusion
rate of 1000 mg per hour.55 (Class I, Level A)
3.9. Ototoxicity has occurred, rarely, in a few dozen case reports in patients receiving vancomycin.55
It may be transient or permanent. It has been reported mostly in patients who have been given
excessive doses, who have an underlying hearing loss, or who are receiving concomitant
therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should be used
with caution in patients with renal insufficiency because the risk of toxicity is appreciably
increased by high, prolonged blood concentrations.56 (Class I, Level A)
3.10. Reversible neutropenia, usually starting 1 week or more after onset of therapy with vancomycin
or after a total dosage of more than 25 grams, has been reported for several dozen patients.
Neutropenia appears to be promptly reversible when vancomycin is discontinued.
Thrombocytopenia has rarely been reported. Although a causal relationship has not been
established, reversible agranulocytosis 3 (granulocytes < 500/mm3).55 (Class I, Level A)
3.11. Infrequently, drug fever, eosinophilia, exfoliative dermatitis, linear IgA bullous dermatosis,
Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, and drug rash with
eosinophilia and systemic symptoms (DRESS) have been reported in association with
administration of vancomycin.55 (Class I, Level A)

4. Vancomycin Therapeutic Drug Concentration Monitoring
4.1. Vancomycin pharmacokinetic and pharmacodynamic activity is best described by the 24-hour
area under the curve to minimum inhibitory concentration (AUC24:MIC) ratio. Animal and human
data indicate that the ratio of area under the curve AUC24:MIC is predictive of clinical outcome
when treating methicillin-resistant Staphylococcus aureus (MRSA).43,53,57 The goal AUC24:MIC
ratio to optimize the chance of microbiological success in the treatment of Staphylococcus
aureus is 400.7,14,20,57 For serious infections, the optimal AUC24:MIC goal may be 600.
4.1.1. The AUC24:MIC goal to successfully treat non-Staphylococcus aureus infections with
vancomycin is not known, but it is likely lower than 400.58 (Class IIb, Level C)
4.1.2. Although not well established, the optimal AUC24:MIC ratio appears to 600 for serious
MRSA infections.8,10,20 (Class IIb, Level C)
4.1.3. An AUC of 700 mg*hr/L represents the best conservative estimate of the upper threshold
of safe vancomycin exposure with a minimal risk of nephrotoxicity. Above this threshold,
the risk of vancomycin toxicity increases rapidly.8
4.2. In patients who are not critically ill and without severe infection, a vancomycin trough
concentration based approach is reasonable to use.9 (Class IIa, Level B)
4.2.1. Vancomycin trough concentration monitoring is subject to a high degree of inter-individual
variability between the measured trough value and the actual AUC, and this therapeutic
discordance may lead to suboptimal clinical outcomes such as treatment failure against
less susceptible pathogens and nephrotoxicity with unnecessarily high doses. Trough
monitoring alone is likely to underestimate the true AUC by up to 33%.8
4.2.2. For severe infections such as meningitis, MRSA osteomyelitis, MRSA bacteremia,
endocarditis, pneumonia due to MRSA, and septic shock the goal trough for intermittent
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


13
dosing is 15-20 mcg/mL.
4.2.2.1. Serum trough concentration targets must be integrated with the clinical
response of the patient. If the target trough is 15-20 mcg/mL per Table 4 and
the trough drawn is slightly below 15 mcg/mL and the patient is making an
adequate clinical response, dose adjustment to achieve a higher trough may
not be always necessary.8,20 (Class IIa, Level C)
4.2.3. For other infections a reasonable goal vancomycin trough for intermittent dosing is 10-20
mcg/mL. To minimize toxicity, it is reasonable for vancomycin trough concentrations for
intermittent dosing to not exceed 15 mcg/mL unless the target trough concentration is 15-
20 mcg/mL.59,60 (Class IIa, Level B)
4.2.4. To avoid both vancomycin resistance development and treatment failure, troughs greater
than 10 mcg/mL should be targeted.61,62 (Class IIa, B)
4.2.5. Vancomycin dosing to achieve troughs greater than 15 mcg/mL, although possibly
warranted to treat more serious infections, is associated with an increased risk of
nephrotoxicity. Troughs greater than 20 mcg/mL have also been associated with
nephrotoxicity.1,14 (Class IIa, Level A)
4.2.5.1. As troughs are a surrogate marker for vancomycin efficacy, they are also a
surrogate marker for vancomycin nephrotoxicity. The true marker for
vancomycin nephrotoxicity risk is likely AUC greater than 700 mg·hr/L.8,14

Table 2. Vancomycin Target Pharmacodynamic Parameters
Treatment Population Target Trough Concentrations Target AUC24:MIC
ξ Infection due to MRSA with a MIC = 1
mcg/mL
ξ Hospital-acquired pneumonia (HAP)
ξ Healthcare-associated pneumonia(HCAP)
ξ Ventilator- associated pneumonia (VAP)
ξ Meningitis treated with intermittent dosing
ξ Endocarditis
ξ MRSA osteomyelitis
ξ Undifferentiated septic shock
ξ Cystic fibrosis exacerbation
15 – 20 mcg/mL 400-700
Infections treated with continuous infusion
vancomycin 20 – 28 mcg/mL 400-700
All other infections 10 – 15 mcg/mL 400-700

4.3. In critically ill patients with severe infections, an equation-based approach can be useful. For
patients with definitive vancomycin therapy for at least 4 days with a target trough of 15-20
mcg/mL, it may be reasonable to consider AUC calculations.9 (Class IIa, Level C)
4.3.1. AUC estimations are performed with two vancomycin concentrations. It is reasonable to
draw the first concentration one to two hours after the end of the infusion and the second
concentration near the end of the first dosing interval. AUC24:MIC can be estimated in
several different ways and may be calculated using equations in Appendix B.12,17,53,57.
(Class IIa, Level B)
4.3.1.1. If the MIC is not known at the time of AUC24:MIC calculation, it is reasonable to
estimate the MIC based on current UWHC antibiogram surveillance data of
Staphylococcus aureus vancomycin MIC distribution (See Appendix C). (Class
IIa, Level C)
4.3.1.2. If a patient has had previous MRSA isolates cultured with an MIC greater than
1 mcg/mL, it is reasonable to use the previous MIC in the AUC24:MIC goal for
empiric treatment. (Class IIa, Level C)
4.4. In cystic fibrosis patients, target vancomycin concentrations of 15-20 mcg/mL are reasonable in
order to target AUC24:MIC of ≥400.46 (Class IIa, Level C)
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


14
4.5. As pharmacokinetic parameters can fluctuate rapidly in a clinically unstable patient, clinicians
should use clinical judgement to determine when vancomycin concentrations should be drawn.
1,9,57

4.5.1. For calculation of an AUC24:MIC, it is reasonable to draw vancomycin concentrations
after any vancomycin dose. (Class IIa, Level C)
4.5.2. For intermittent trough concentration monitoring, it is reasonable to consider drawing a
vancomycin concentration prior to the fourth or fifth dose. For patients on infrequent
dosing schedules (frequency of every 24 hours or longer) it may be reasonable to draw a
vancomycin concentration sooner than the fourth or fifth dose. (Class IIa, Level C)
4.5.3. Patients with rapidly changing renal function in whom vancomycin kinetics are difficult to
predict may be candidates for alternatives to vancomycin. (Class IIa, Level B)
4.6. In response to a supratherapeutic or subtherapeutic vancomycin trough concentration or
AUC24:MIC, it can be effective to adjust the total vancomycin daily dose in a proportional fashion
due to the linear kinetics of vancomycin. Consideration may also be given to changing the
dosing interval. (Class IIa, Level C)
4.7. Therapeutic drug monitoring of vancomycin is probably indicated on a weekly basis in patients
with stable hemodynamics and renal function. In unstable patients it is probably indicated to
have drug concentrations checked more frequently. (Class IIa, Level B)
4.7.1. There is no evidence that obtaining daily vancomycin concentrations during therapy will
be useful and this will likely result in unnecessarily increased cost.

5. Vancomycin in renal replacement therapy
5.1. Inpatient intermittent hemodialysis (HD)
5.1.1. It may be reasonable for inpatients on intermittent HD to receive a loading dose of 20
mg/kg (dose capped at 2000 mg) based on an estimated dry weight at the time of order
initiation if it is anticipated for there to be 24 hours between the loading dose and the next
HD session.63-66 (Class IIb, Level C)
5.1.2. It may be reasonable to use a loading dose of 25 mg/kg (dose capped at 2000 mg ) if it is
anticipated for there to be 48 hours between the loading dose and next HD session.63
(Class IIb, Level C)
5.1.3. Scheduled post-dialysis maintenance doses may be considered to prevent unintentional
delays or omissions during vancomycin therapy.
5.1.4. Patients receiving dialysis are highly variable (ranging from chronic anuric HD patients to
temporary intermittent HD patients to peritoneal dialysis) and these factors may be
considered when evaluating vancomycin dosing. (Class IIb, Level C)
5.1.5. It may be reasonable to monitor vancomycin for HD patients to account for variables that
can influence clearance, including residual renal function, complex elimination kinetics
(intradialytic phase, post-rebound phase and interdialytic phase), dialyzer membrane
type, dialyzer reprocessing and reuse, dialysis blood flow rate, dialysis solution flow rate
and length of HD sessions.67-69 (Class IIb, Level C)
5.1.6. For scheduled, chronic (three times weekly) HD patients, it may be reasonable to
consider patient weight and residual renal function when empirically choosing a post-HD
maintenance dose.63 (Class IIb, Level C).
5.1.6.1. Maintenance doses for chronic HD patients typically range from 500 mg to
1000 mg.
5.1.6.2. A 500 mg initial maintenance dose may be considered for a small (50-70 kg),
anuric adult patient.66,70
5.1.6.3. A 750 to 1000 mg maintenance dose may be considered for larger patients or
patients with residual renal function.67,71,72 (Class IIb, Level C)
5.1.7. After the initial loading dose is given, it may be reasonable to draw a post-HD
vancomycin trough no sooner than two hours after the end of the next HD session,
although it is preferable to draw three hours after the end of the session to allow maximal
redistribution and plasma rebound.68 (Class IIb, Level C)
5.1.8. Maintenance dose adjustment may be considered for any post-HD trough that is less
than the limit of the therapeutic goal range as shown in Table 2.66
5.1.8.1. It may be reasonable to hold the post-HD dose if the trough is greater than the
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


15
upper limit of the therapeutic.
5.1.8.1.1. If the dose is held, it is reasonable to reduce the next scheduled
post-HD maintenance dose.63,73 (Class IIb, Level B)
5.1.8.2. A vancomycin dose may be reasonable even if the post-HD concentration is
within the target range, since vancomycin clearance still occurs outside of the
HD session both by renal mechanisms (residual renal function) and minor non-
renal mechanisms.

5.2. Continuous renal replacement therapy (CRRT)
5.2.1. Patients receiving CRRT should be managed following the UWHC Guideline for
Continuous Renal Replacement Therapy Based Dosing Adjustments.

6. Continuous infusion vancomycin
6.1. Vancomycin administration can beneficial via continuous infusion in documented or highly
suspected Gram-positive organism ventriculoperitoneal shunt or meningeal infections. (Class IIa,
Level B)
6.2. Continuous infusion vancomycin is generally not recommended for the treatment of other
infections due to lack of evidence. However, in critically ill patients with severe infections,
sepsis, and ventilator-associated pneumonia, the use of continuous infusion vancomycin has
been found to achieve target trough and the target AUC24:MIC ratios more frequently than
patients receiving intermittent infusion vancomycin. Providers may consider continuous infusion
vancomycin for non-central nervous system infections at their discretion.74-76 (Class IIb, Level C).
6.2.1. Continuous infusion vancomycin may be considered less nephrotoxic than intermittent
infusion vancomycin.77 (Class IIb, Level B)
6.3. Continuous infusion vancomycin is not intended for empiric therapy of community-acquired
pneumococcal meningitis in the absence of a positive Gram stain, CSF antigen or culture.
Distribution into the cerebral spinal fluid is poor unless the meninges are inflamed.78 Penetration
of vancomycin in the CNS is limited by its hydrophilicity, relatively large molecular weight, and in
part because it crosses the blood-brain barrier by paracellular pathways. Peak concentrations of
vancomycin in the CNS are delayed compared to vancomycin concentrations, and the
elimination half-life of vancomycin in the CNS is longer than in the serum.79
6.4. A 25 mg/kg (maximum 2000 mg) loading dose with of vancomycin may be considered prior to
the initiation of continuous infusion vancomycin.80 (Class IIb, Level C)
6.5. Total body weight is reasonable to use for dose calculations for patients with a BMI below 30
kg/m2. For patients with a BMI greater than or equal to 30 kg/m2, it is reasonable to use adjusted
body weight for dose calculations. (Class IIa, Level C)
6.6. It may be reasonable to use Initial dosing be based on the nomogram in Table 3.77,81 (Class IIb,
Level B

Table 3. Continuous Infusion Vancomycin Dosing
Estimated Creatinine
Clearance Loading Dose Continuous infusion
>90 mL/min 25 mg/kg (maximum 2000 mg) 45 mg/kg/24 hours
75-89 mL/min 25 mg/kg (maximum 2000 mg) 35 mg/kg/24 hours
60-74 mL/min 25 mg/kg (maximum 2000 mg) 30 mg/kg/24 hours
45-59 mL/min 25 mg/kg (maximum 2000 mg) 25mg/kg/24 hours
<45 mL/min Intermittent traditional dosing is preferred

6.7. The continuous infusion may be started as soon as the loading dose is complete.77,81 (Class IIb,
Level B)
6.7.1. The continuous infusion should be prepared in normal saline (0.9% sodium chloride).
6.7.1.1. The calculated 24-hour dose should be added to a 500 mL or 1000 mL bag of
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


16
normal saline and the infusion rate calculated from the total volume of antibiotic
plus diluent divided by 24 hours.
6.7.2. For peripheral administration it is reasonable for the final concentration of the product to
be less than or equal to 5 mg/mL.55 (Class IIb, Level C)
6.8. Vancomycin concentration monitoring is not recommended until at least 24 hours after the
continuous infusion has begun or 24 hours after dose adjustments.1,43,53 (Class IIa, Level C)
6.8.1. Reasonable target steady-state concentrations for continuous infusion vancomycin for
meningitis are 20-28 mcg/mL (See Table 2).77 (Class IIa, Level B)
6.8.2. Dose adjustments should be made in 250 mg/day intervals.
6.8.3. Once steady-state is attained, further vancomycin concentration monitoring likely is not
indicated unless there are significant changes in renal function or body weight.
6.8.3.1. In patients with normal renal function the vancomycin half-life ranges from 6 to
12 hours; as a result it can take up to 60 hours to reach steady state in patients
with normal renal function and even longer in patients with renal compromise.43
6.9. If the vancomycin plateau concentration is above 30 mcg/mL, it is reasonable to pause the
continuous infusion adjust as described in Table 4.77,81 (Class IIb, Level B)

Table 4. Adjustments for Continuous Vancomycin Infusions with Vancomycin Plateaus above 30
mcg/mL
Creatinine Clearance Vancomycin plateau
30-32 mcg/mL
Vancomycin plateau
33-36 mcg/mL
Vancomycin plateau
37-40 mcg/mL
>90 mL/min
Hold infusion for 2
hours; decrease daily
dose by 20%
Hold infusion for 3
hours; decrease daily
dose by 25%
Hold infusion for 4
hours, decrease daily
dose by 35%
75-89 mL/min
Hold infusion for 4
hours: decrease daily
dose by 20%
Hold infusion for 5
hours; decrease daily
dose by 25%
Hold infusion for 6
hours; decrease daily
dose by 35%
60-74 mL/min
Hold infusion for 6
hours; decrease dose by
20%
Hold infusion for 8
hours; decrease daily
dose by 25%
Hold infusion 10 hours;
decrease daily dose by
35%
45-59 mL/min
Hold infusion for 8
hours; decrease dose by
20%
Hold infusion for 10
hours; decrease daily
dose by 25%
Hold infusion for 12
hours; decrease dose by
35%

UW Health Implementation
1. Pharmacists will be educated about these guidelines via-department in-services
2. Emergency Department and inpatient order sets will be updated
3. Physicians will be educated via resident learning sessions (held monthly), clinical decision
support in HealthLink, and via the best practice alert notification system used by the Antimicrobial
Stewardship Team.

Disclaimer
This Clinical Practice Guideline provides an evidence-based approach for the use of vancomycin. It is
understood that occasionally patients will not match the conditions considered in the guideline



Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


17

Appendix A. Vancomycin Guideline Flow Chart 1,9,43,59,66,73,80,82-84
Decision to order
vancomycin
Is
vancomycin
indicated?
Documented or highly
suspected Gram positive
organism causing
ventriculoperitoneal
shunt or meningitis
infection
Sepsis, septic shock
indication without
HD
Non-sepsis
indication without
HD
Start continuous
infusion according to
Table 3 within 2
hours after loading
dose complete
Vancomycin serum
concentrations ≥ 24
hours after start of
infusion
LD: 25 mg/kg,
maximum 2000 mg/
dose
Dose adjust per
Table 4
LD 25 mg/kg,
maximum 2000 mg/
dose, followed by
MD according to
Table 1
AUC:MIC or
trough-only
monitoring
Calculate AUC or
AUC:MIC (if
available) and adjust
to goal
If indicated, draw a
trough before 4
th
or
5
th
dose and adjust
to goal per Table 2
Clinical
improvement,
stable CrCl and
UOP, no toxicity,
expected duration
< 4 days
Yes No
No additional
vancomycin
monitoring required
Clinicians should use
clinical judgement
and communicate
with the primary
team to determine
when or if
vancomycin levels
should be drawn
LD 25 mg/kg,
maximum 2000 mg/
dose, followed by
MD according to
Table 1
Indication for
TDM per section
3.3
Draw a trough
before 4
th
or 5
th
dose
and adjust to goal
per Table 2
No TDM indicated,
do not draw a
trough
No
Yes
Renal replacement
therapy with or
without sepsis,
septic shock
Does patient
now require
RRT?
No
Yes
Does patient
now require
RRT?
No
Yes
HD or CRRT
Yes
No
CRRTHD
LD of 15 mg/kg and
MD of 10 mg/kg
every 12 hours. All
doses capped at
2000 mg
Time between
loading dose and
next HD session?
LD: 20 mg/
kg (2000 mg
cap)
LD: 25 mg/kg
(2000 mg
cap)
48
hours
24
hours
Draw a level no
sooner than 2 hours
post-HD (3 hours
preferable)
Is patient <70 kg
and anuric?
Start 500 mg
MD post-HD
Start 750-1000 mg
MD post-HD
depending on weight
on residual renal
function
Yes
Check a post-HD
level after the first
MD
Adjust MD as
needed to goal per
Table 2
LEGEND
HD: hemodialysis
CRRT: continuous renal replacement
therapy
RRT: renal replacement therapy
LD: loading dose
MD: maintenance dose
TDM: therapeutic drug monitoring
AUC: area under the curve
MIC: minimum inhibitor
concentration
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


18
Appendix B. Vancomycin Pharmacokinetic Equations85



858585848483







Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


19
Appendix C. Characterization of Vancomycin MICs against Staphylococcus
Aureus
MICs of vancomycin against Staphylococcus aureus isolates from blood, catheter tip, sputum,
bronchioalveolar lavage, bone, and cerebrospinal fluids from 1/1/2013 to 4/12/2015 at UWHC
are characterized below:






























Total Adult
Inpatient Isolates
Adult Intensive
Care Units
All Adult Non-
Intensive Care
Units
B4/6 B6/6
MIC
0.5
1% (8/1026) 0% (2/422) 1% (6/604) 30% (3/10) 0% (0/35)
MIC 1 87% (888/1026) 89% (377/422) 85% (511/604) 70% (7/10) 91% (32/35)
MIC
1.5
2% (17/1026) 1% (3/422) 2% (14/604) 0% (0/10) 0% (0/35)
MIC 2 11% (113/1026) 9% (40/422) 12% (73/604) 0% (0/10) 9% (3/35)
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


20
References
1. 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. Jan 1
2009;66(1):82-98.
2. Laxminarayan R, Duse A, Wattal C, et al. Antibiotic resistance-the need for global solutions. Lancet Infect
Dis. Dec 2013;13(12):1057-1098.
3. Schleyer AM, Jarman KM, Chan JD, Dellit TH. Role of nasal methicillin-resistant Staphylococcus aureus
screening in the management of skin and soft tissue infections. American journal of infection control. Oct
2010;38(8):657-659.
4. Win MK, Yung CF, Poh BF, et al. Evaluation of universal methicillin-resistant Staphylococcus aureus
screening using nasal polymerase chain reaction compared with nasal, axilla, and groin and throat and
perianal cultures in a hospital setting. Infection control and hospital epidemiology : the official journal of the
Society of Hospital Epidemiologists of America. Dec 2013;34(12):1335-1337.
5. Dangerfield B, Chung A, Webb B, Seville MT. Predictive value of methicillin-resistant Staphylococcus aureus
(MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother. 2014;58(2):859-864.
6. Lavery LA, Fontaine JL, Bhavan K, Kim PJ, Williams JR, Hunt NA. Risk factors for methicillin-resistant
Staphylococcus aureus in diabetic foot infections. Diabet Foot Ankle. Vol 5. Sweden2014.
7. Holmes NE, Turnidge JD, Munckhof WJ, et al. Vancomycin AUC/MIC ratio and 30-day mortality in patients
with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. Apr 2013;57(4):1654-1663.
8. Neely MN, Youn G, Jones B, et al. Are vancomycin trough concentrations adequate for optimal dosing?
Antimicrob Agents Chemother. 2014;58(1):309-316.
9. Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in
individual patients. Advanced drug delivery reviews. Jun 5 2014.
10. Lodise TP, Drusano GL, Zasowski E, et al. Vancomycin exposure in patients with methicillin-resistant
Staphylococcus aureus bloodstream infections: how much is enough? Clin Infect Dis. Sep 1 2014;59(5):666-
675.
11. Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP. Vancomycin: we can't get there from
here. Clin Infect Dis. Apr 15 2011;52(8):969-974.
12. Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with
various degrees of renal function. Antimicrob Agents Chemother. Apr 1984;25(4):433-437.
13. Murphy JE, Gillespie DE, Bateman CV. Predictability of vancomycin trough concentrations using seven
approaches for estimating pharmacokinetic parameters. Am J Health Syst Pharm. Dec 1 2006;63(23):2365-
2370.
14. Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with
methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested
targets. Clin Infect Dis. Apr 15 2011;52(8):975-981.
15. Kullar R, Leonard SN, Davis SL, et al. Validation of the effectiveness of a vancomycin nomogram in
achieving target trough concentrations of 15-20 mg/L suggested by the vancomycin consensus guidelines.
Pharmacotherapy. May 2011;31(5):441-448.
16. Kullar R, Davis SL, Taylor TN, Kaye KS, Rybak MJ. Effects of targeting higher vancomycin trough levels on
clinical outcomes and costs in a matched patient cohort. Pharmacotherapy. Mar 2012;32(3):195-201.
17. DeRyke C, Alexander D. Optimizing vancomycin dosing through pharmacodynamic assessment targeting
area under the concentration-time curve/minimum inhibitory concentration. Vol 44. Hospital
Pharmacy2009:751-765.
18. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america
for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect
Dis. Feb 1 2011;52(3):e18-55.
19. Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC, Jr., Eliopoulos GM. Relationship of
MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus
aureus bacteremia. J Clin Microbiol. Jun 2004;42(6):2398-2402.
20. Zelenitsky S, Rubinstein E, Ariano R, et al. Vancomycin pharmacodynamics and survival in patients with
methicillin-resistant Staphylococcus aureus-associated septic shock. International journal of antimicrobial
agents. Mar 2013;41(3):255-260.
21. Tricoci P, Allen JM, Kramer JM, Califf RM, Smith SC, Jr. Scientific evidence underlying the ACC/AHA clinical
practice guidelines. JAMA : the journal of the American Medical Association. Feb 25 2009;301(8):831-841.
22. Prevention CfDCa. Body Mass Index2015.
23. Pai MP, Paloucek FP. The origin of the "ideal" body weight equations. Ann Pharmacother. Sep
2000;34(9):1066-1069.
24. Pinna K, Whitney EN. Nutrition and Diet Therapy. 8th ed2011.
25. Del Parigi A. Definitions and Classification of Obesity. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al.,
eds. Endotext. South Dartmouth MA: MDText.com, Inc.; 2000.
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


21
26. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-
41.
27. Cheriex EC, Leunissen KM, Janssen JH, Mooy JM, van Hooff JP. Echography of the inferior vena cava is a
simple and reliable tool for estimation of 'dry weight' in haemodialysis patients. Nephrol Dial Transplant.
1989;4(6):563-568.
28. Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. Mayo Clin Proc. Vol 86. United
States2011:156-167.
29. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for
management of severe sepsis and septic shock: 2012. Crit Care Med. Vol 41. United States2013:580-637.
30. Boyce JM, Pop OF, Abreu-Lanfranco O, et al. A trial of discontinuation of empiric vancomycin therapy in
patients with suspected methicillin-resistant Staphylococcus aureus health care-associated pneumonia.
Antimicrob Agents Chemother. Mar 2013;57(3):1163-1168.
31. Bosch K, McLaughlin MM, Esterly JS, Rhodes NJ, Postelnick MJ, Scheetz MH. Impact of vancomycin
treatment duration and dose on kidney injury. Int J Antimicrob Agents. Mar 2014;43(3):297-298.
32. Lu CL, Liu CY, Huang YT, et al. Antimicrobial susceptibilities of commonly encountered bacterial isolates to
fosfomycin determined by agar dilution and disk diffusion methods. Antimicrob Agents Chemother. Sep
2011;55(9):4295-4301.
33. Suzuki Y, Kawasaki K, Sato Y, et al. Is peak concentration needed in therapeutic drug monitoring of
vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant
staphylococcus aureus pneumonia. Chemotherapy. 2012;58(4):308-312.
34. Rosini JM, Laughner J, Levine BJ, Papas MA, Reinhardt JF, Jasani NB. A randomized trial of loading
vancomycin in the emergency department. Ann Pharmacother. Jan 2015;49(1):6-13.
35. Lamp KC, Rybak MJ, Bailey EM, Kaatz GW. In vitro pharmacodynamic effects of concentration, pH, and
growth phase on serum bactericidal activities of daptomycin and vancomycin. Antimicrob Agents
Chemother. Dec 1992;36(12):2709-2714.
36. Peetermans WE, Hoogeterp JJ, Hazekamp-van Dokkum AM, van den Broek P, Mattie H. Antistaphylococcal
activities of teicoplanin and vancomycin in vitro and in an experimental infection. Antimicrob Agents
Chemother. Oct 1990;34(10):1869-1874.
37. Demirovic JA, Pai AB, Pai MP. Estimation of creatinine clearance in morbidly obese patients. Am J Health
Syst Pharm. Vol 66. United States2009:642-648.
38. Spinler SA, Nawarskas JJ, Boyce EG, Connors JE, Charland SL, Goldfarb S. Predictive performance of ten
equations for estimating creatinine clearance in cardiac patients. Iohexol Cooperative Study Group. The
Annals of pharmacotherapy. Dec 1998;32(12):1275-1283.
39. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the
bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. Jul 2012;32(7):604-612.
40. Wilhelm SM, Kale-Pradhan PB. Estimating creatinine clearance: a meta-analysis. Pharmacotherapy. Jul
2011;31(7):658-664.
41. Salazar DE, Corcoran GB. Predicting creatinine clearance and renal drug clearance in obese patients from
estimated fat-free body mass. The American journal of medicine. Jun 1988;84(6):1053-1060.
42. Karam CM, McKinnon PS, Neuhauser MM, Rybak MJ. Outcome assessment of minimizing vancomycin
monitoring and dosing adjustments. Pharmacotherapy. Mar 1999;19(3):257-266.
43. Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis. Jan 1
2006;42 Suppl 1:S35-39.
44. Moellering RC, Jr. Pharmacokinetics of vancomycin. J Antimicrob Chemother. Dec 1984;14 Suppl D:43-52.
45. Pleasants RA, Michalets EL, Williams DM, Samuelson WM, Rehm JR, Knowles MR. Pharmacokinetics of
vancomycin in adult cystic fibrosis patients. Antimicrob Agents Chemother. Jan 1996;40(1):186-190.
46. Fusco NM, Toussaint KA, Prescott WA, Jr. Antibiotic management of methicillin-resistant Staphylococcus
aureus--associated acute pulmonary exacerbations in cystic fibrosis. The Annals of pharmacotherapy. Apr
2015;49(4):458-468.
47. van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced
nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per
liter. Antimicrob Agents Chemother. Feb 2013;57(2):734-744.
48. Carreno JJ, Kenney RM, Lomaestro B. Vancomycin-Associated Renal Dysfunction: Where Are We Now?
Pharmacotherapy. Sep 15 2014.
49. Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin
concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. Aug 15
2009;49(4):507-514.
50. Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least four grams per day) are
associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. Apr
2008;52(4):1330-1336.
51. Meaney CJ, Hynicka LM, Tsoukleris MG. Vancomycin-associated nephrotoxicity in adult medicine patients:
incidence, outcomes, and risk factors. Pharmacotherapy. Jul 2014;34(7):653-661.
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


22
52. Sivagnanam S, Deleu D. Red man syndrome. Critical care (London, England). Apr 2003;7(2):119-120.
53. Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of beta-lactams,
glycopeptides, and linezolid. Infectious disease clinics of North America. Sep 2003;17(3):479-501.
54. Renz CL, Thurn JD, Finn HA, Lynch JP, Moss J. Antihistamine prophylaxis permits rapid vancomycin
infusion. Crit Care Med. Sep 1999;27(9):1732-1737.
55. Pfizer. Vancomycin [Package Insert]2010.
56. Bailie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity. A review. Medical toxicology and adverse
drug experience. Sep-Oct 1988;3(5):376-386.
57. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other
antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet.
2004;43(13):925-942.
58. Safdar N, Andes D, Craig WA. In vivo pharmacodynamic activity of daptomycin. Antimicrob Agents
Chemother. Jan 2004;48(1):63-68.
59. Wong-Beringer A, Joo J, Tse E, Beringer P. Vancomycin-associated nephrotoxicity: a critical appraisal of
risk with high-dose. International journal of antimicrobial agents. Feb 2011;37(2):95-101.
60. Hanrahan TP, Harlow G, Hutchinson J, et al. Vancomycin-associated nephrotoxicity in the critically ill: a
retrospective multivariate regression analysis*. Crit Care Med. Dec 2014;42(12):2527-2536.
61. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america
for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect
Dis. Vol 52. United States2011:e18-55.
62. Tsuji BT, Rybak MJ, Lau KL, Sakoulas G. Evaluation of accessory gene regulator (agr) group and function in
the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus. Antimicrob Agents
Chemother. Mar 2007;51(3):1089-1091.
63. Vandecasteele SJ, De Vriese AS. Vancomycin dosing in patients on intermittent hemodialysis. Semin Dial.
Jan-Feb 2011;24(1):50-55.
64. Brown M, Polisetty R, Gracely EJ, Cuhaci B, Schlecht HP. Weight-based loading of vancomycin in patients
on hemodialysis. Clin Infect Dis. Vol 53. United States2011:164-166.
65. El Nekidy WS, El-Masri MM, Umstead GS, Dehoorne-Smith M. Factors influencing vancomycin loading dose
for hospitalized hemodialysis patients: prospective observational cohort study. Can J Hosp Pharm. Nov
2012;65(6):436-442.
66. Barth RH, DeVincenzo N. Use of vancomycin in high-flux hemodialysis: experience with 130 courses of
therapy. Kidney international. Sep 1996;50(3):929-936.
67. Pallotta KE, Manley HJ. Vancomycin use in patients requiring hemodialysis: a literature review. Semin Dial.
Vol 21. United States2008:63-70.
68. Welage LS, Mason NA, Hoffman EJ, et al. Influence of cellulose triacetate hemodialyzers on vancomycin
pharmacokinetics. J Am Soc Nephrol. Oct 1995;6(4):1284-1290.
69. Meyer CC, Calis KA. New hemodialysis membranes and vancomycin clearance. Am J Health Syst Pharm.
Dec 15 1995;52(24):2794-2796.
70. Lin SY, Shen MC, Hwang SJ, et al. Evaluation of vancomycin dosing protocols to achieve therapeutic serum
concentrations in patients receiving high-flux haemodialysis. Int J Antimicrob Agents. Apr 2014;43(4):384-
385.
71. Mason NA, Neudeck BL, Welage LS, Patel JA, Swartz RD. Comparison of 3 vancomycin dosage regimens
during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration. Clin
Nephrol. Aug 2003;60(2):96-104.
72. Taylor ME, Allon M. Practical vancomycin dosing in hemodialysis patients in the era of emerging
vancomycin resistance: a single-center experience. Am J Kidney Dis. Vol 55. United States2010:1163-1165.
73. Pai AB, Pai MP. Vancomycin dosing in high flux hemodialysis: a limited-sampling algorithm. American
journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System
Pharmacists. Sep 1 2004;61(17):1812-1816.
74. Blot S, Koulenti D, Akova M, et al. Does contemporary vancomycin dosing achieve therapeutic targets in a
heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study. Crit Care.
2014;18(3):R99.
75. Saugel B, Gramm C, Wagner JY, et al. Evaluation of a dosing regimen for continuous vancomycin infusion
in critically ill patients: an observational study in intensive care unit patients. J Crit Care. Jun 2014;29(3):351-
355.
76. Schmelzer TM, Christmas AB, Norton HJ, Heniford BT, Sing RF. Vancomycin intermittent dosing versus
continuous infusion for treatment of ventilator-associated pneumonia in trauma patients. Am Surg. Nov
2013;79(11):1185-1190.
77. DiMondi VP, Rafferty K. Review of continuous-infusion vancomycin. The Annals of pharmacotherapy. Feb
2013;47(2):219-227.
78. Albanese J, Leone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C. Cerebrospinal fluid penetration and
pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in
Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org


23
an intensive care unit. Antimicrob Agents Chemother. May 2000;44(5):1356-1358.
79. Cubist. Cubicin[Package Inset]2014.
80. Saugel B, Nowack MC, Hapfelmeier A, et al. Continuous intravenous administration of vancomycin in
medical intensive care unit patients. J Crit Care. Feb 2013;28(1):9-13.
81. Pea F, Furlanut M, Negri C, et al. Prospectively validated dosing nomograms for maximizing the
pharmacodynamics of vancomycin administered by continuous infusion in critically ill patients. Antimicrob
Agents Chemother. May 2009;53(5):1863-1867.
82. Foote EF, Dreitlein WB, Steward CA, Kapoian T, Walker JA, Sherman RA. Pharmacokinetics of vancomycin
when administered during high flux hemodialysis. Clinical nephrology. Jul 1998;50(1):51-55.
83. Davis SL, Scheetz MH, Bosso JA, Goff DA, Rybak MJ. Adherence to the 2009 consensus guidelines for
vancomycin dosing and monitoring practices: a cross-sectional survey of U.S. hospitals. Pharmacotherapy.
Dec 2013;33(12):1256-1263.
84. Ariano RE, Fine A, Sitar DS, Rexrode S, Zelenitsky SA. Adequacy of a vancomycin dosing regimen in
patients receiving high-flux hemodialysis. American journal of kidney diseases : the official journal of the
National Kidney Foundation. Oct 2005;46(4):681-687.
85. Pai MP, Russo A, Novelli A, Venditti M, Falcone M. Simplified equations using two concentrations to
calculate area under the curve for antimicrobials with concentration-dependent pharmacodynamics:
daptomycin as a motivating example. Antimicrob Agents Chemother. Vol 58. United States: American
Society for Microbiology. All Rights Reserved.; 2014:3162-3167.


Copyright © 2016 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
09/2016CCKM@uwhealth.org