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Clinical Monitoring of Outpatient Parenteral Antimicrobial Therapy (OPAT) and Selected Oral Antimicrobial Agents – Adult – Inpatient/Ambulatory

Clinical Monitoring of Outpatient Parenteral Antimicrobial Therapy (OPAT) and Selected Oral Antimicrobial Agents – Adult – Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Infection and Isolation


UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG 1
Clinical Monitoring of Outpatient Parenteral
Antimicrobial Therapy (OPAT) and Selected
Oral Antimicrobial Agents – Adult –
Inpatient/Ambulatory – Clinical Practice
Guideline
Table of Contents
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE: ..................................................................................................................................... 4
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS ............................................................................................................................ 6
INTRODUCTION ....................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................. 6
TABLE 1: RECOMMENDATIONS FOR OPAT AND SELECTED ORAL ANTIMICROBIAL
AGENTS MONITORING ............................................................................................................ 7
ANTIBIOTIC AGENTS ............................................................................................................... 9
ANTIFUNGALS ........................................................................................................................10
ANTIVIRALS ............................................................................................................................11
REFERENCES .........................................................................................................................12
APPENDIX A. COORDINATING AN OPAT DISCHARGE .......................................................14
CPG Contact for Changes: CPG Contact for Content:
Name: Philip Trapskin, Pharm D, BCPS Name: Lucas Schulz, PharmD, BCPS AQ-ID
Phone Number: (608) 263-1328 Email Address: lschulz2@uwhealth.org
Email Address: ptrapskin@uwhealth.org
Note: Active Table of Contents
Click to follow link
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

2
Guideline Author(s):
Luiza Kerstenetzky, DPH-4; Erin McCreary, PharmD, BCPS; Lucas Schulz, PharmD,
BCPS AQ-ID; Joshua Vanderloo, PharmD

Coordinating Team Members:
Joshua Vanderloo, PharmD

Review Individuals/Bodies:
David Andes, MD; Barry Fox, MD; Alexander Lepak, MD; Jeannina Smith, MD; Teresa
Darcy, MD, MMM
Tyler Liebenstein, PharmD, BCPS; Marie Pietruszka, PharmD, BCPS, CNSC; Jill
Strayer, PharmD

Committee Approvals/Dates:
UW Health Lab Practice Committee, January 2015
Antimicrobial Use Subcommittee, February 2015
Interim Revisions: November 2016
P&T Committee, February 2015
Interim Revisions: December 2016

Release Date: December 2016

Next Review Date: March 2018
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

3
Executive Summary

Guideline Overview
This document is intended to guide the laboratory monitoring of patients discharging on
intravenous antimicrobials. Principles from the IDSA guidelines along with more recent evidence
are incorporated in provided recommendations.

Target Population
Adults requiring antimicrobials in an outpatient setting

Key Revisions (Interim Update December 2016)
1. Addition of Appendix A to include guidance for coordination of discharge prescriptions
and workflow for patients discharging with OPAT.

Key Practice Recommendations
Antimicrobials addressed in this guideline include:
- Aminoglycosides
- Beta-lactams
- Fluoroquinolones
- Daptomycin
- Linezolid
- Trimethoprim-sulfamethoxazole
- Glycopeptides
- Amphotericin B
- Echinocandins
- Azole antifungals
- Ganciclovir
- Acyclovir
- Foscarnet
- Cidofovir

Companion Documents
ξ UWHC Guidelines for the Pharmacokinetic/Pharmacodynamic Dose Optimization of
$QWLELRWLFV��ȕ-lactams, aminoglycosides, and ciprofloxacin) for the Treatment of Gram-
Negative Infections in Adults
ξ UWHC Guidelines for the Intravenous Administration of Formulary Medications in Adults


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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

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Scope:
This document is intended to guide laboratory monitoring of adults prescribed OPAT and
selected oral antimicrobial agents.

Disease/Condition(s):
Bacterial, fungal, or viral infections requiring intravenous antimicrobial in an outpatient setting

Clinical Specialty:
Infectious Disease

Intended Users:
Inpatient and outpatient physicians, pharmacists, nurses, primary care providers, and any other
members of the healthcare team who may participate in management of patients receiving
outpatient antimicrobial therapy

CPG objective:
To communicate evidence-based recommendations for OPAT laboratory monitoring

Target Population:
Adults requiring antimicrobials in an outpatient setting

Interventions and Practices Considered:
Ordering of laboratory tests

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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

5
Methodology
Methods Used to Assess the Quality and Strength of the Evidence:
A modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology Foundation
has been used to assess the Quality and Strength of the Evidence in this Clinical Practice
Guideline (Figure 1).1



Methods Used to Collect/Select the Evidence:
Reviewed the Infectious Diseases Society of America (IDSA) OPAT practice guideline and cited
sources, reviewed manufacturer product labeling, reviewed tertiary references and consulted
with internal infectious disease physicians and pharmacists

Methods Used to Formulate the Recommendations:
Available evidence collected was compiled into a draft document for review by content experts
on various committees (Antimicrobial Use Subcommittee, Pharmacy and Therapeutics
Committee, Laboratory Committee)



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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

6
Definitions2
1. OPAT: the provision of parenteral antimicrobial therapy in at least 2 doses on different days
without intervening hospitalization
2. Outpatient: varied settings in which intravenous antimicrobial therapy can be provided
ZLWKRXW�DQ�RYHUQLJKW�VWD\�LQ�D�KRVSLWDO��7KHVH�LQFOXGH��KRPH��SK\VLFLDQ¶V�RIILFHV��KRVSital-
based ambulatory-care clinics, emergency departments, hemodialysis units, freestanding
infusion centers, skilled nursing or long-term care facilities, and rehabilitation centers.
3. Parenteral: intravenous, subcutaneous, and intramuscular routes of administrations
4. Antimicrobial: antiviral, antifungal, and antibacterial medications
5. Caregiver: any family member, friend, or paid nonprofessional individual with the ability and
willingness to administer treatment and to observe and report significant side effects
A. Introduction
The growth of outpatient parenteral antimicrobial therapy (OPAT) has been fueled by a variety
of factors including the development of antimicrobial agents that can be administered once
daily, technological advances in vascular access and infusion devices, and availability of reliable
and skilled services for OPAT in the community.2 Initiation of OPAT requires that a physician
determine that such therapy is needed to treat an infection for which hospitalization is not
needed, and alternate routes of drug delivery are not feasible or appropriate. The healthcare
team responsible for administration and monitoring of OPAT should appropriately monitor
patients to avoid and address poor clinical responses, therapeutic failure, adverse effects, drug
toxicity, or infusion device and vascular access issues. The Infectious Disease Society of
America Practice Guidelines (IDSA) for OPAT describes the key elements in the appropriate
and safe administration of parenteral antimicrobial therapy in the outpatient setting.2 The
gXLGHOLQH¶V recommendations are often based on expert opinion and further studies may be
needed for determination of the response to therapy. Additional laboratory testing to monitor for
efficacy of OPAT may be warranted based on individual patient characteristics. More frequent
monitoring of laboratory parameters may be indicated if the healthcare team detects a trend
toward toxicity or if an antimicrobial is given over an extended period of time.3
B. Recommendations

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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

7
Table 1a,b: Recommendations for OPAT and selected oral antimicrobial agents monitoring2,3

CBC with
differential
Creatinine and
BUN Electrolytes
c
Liver Enzymesd Drug Concentration Other
Frequency of Testing per Week
Aminoglycosides
ξ gentamicin
ξ tobramycin
ξ amikacin
Once Twice
Drug
concentration(s)
initially, weekly (for
traditional and
synergy dosing),
and as indicated by
increasing
creatinine5
Clinical monitoring
for vestibular and
hearing
dysfunction at each
visit;
Beta-lactams
ξ penicillins
ξ cephalosporins
ξ aztreonam
ξ carbapenems
ξ piperacillin-tazobactam
Once Once
Once weekly with
oxacillin,
nafcillin and
carbapenems

Monitor for delayed
hemolytic anemia
by CBC with
ceftaroline12
Fluoroquinolones
ξ ciprofloxacin
ξ levofloxacin
ξ moxifloxacin
Once13 Once13 Once


Daptomycin Once Once Once CPK approximately weekly
Linezolid Once
Trimethoprim-sulfamethoxazole
(high dose, >10 mg/kg TMP
component)
Once Once Once: Potassium


Glycopeptides
ξ vancomycin
ξ dalbavancin
ξ oritavancin
Once Once
Vancomycin drug
concentration(s)
should ideally be
monitored weekly or
more frequently as
indicated by rising
creatinine

Antifungals
Amphotericin B, including lipid
formulations Once Twice
Twice: electrolytes
Once: Magnesium Once


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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

8

CBC with
differential
Creatinine and
BUN Electrolytes
c
Liver Enzymesd Drug Concentration Other
Frequency of Testing per Week
Azole antifungals
ξ fluconazole
ξ voriconazole
ξ posaconazole (oral)
ξ itraconazole (oral)
ξ isavuconazole (oral)
Once Once
Once; fluconazole
and itraconazole
LFT may be
monitored monthly if
normal at baseline,
and voriconazole
biweekly or monthly
once a stable
pattern identified3
Steady state drug
concentration levels
should be
considered after
prophylaxis or
therapy initiation,
dose changes, or
patient condition
changes for
voriconazole,
itraconazole, and
posaconazole.26

Echinocandins
ξ caspofungin
ξ micafungin
ξ anidulafungin
Once29,30
Once; when steady
state established,
can be monitored
biweekly or monthly


Antivirals
Ganciclovir Twice Twice32 Twice: electrolytes32
Monitor labs twice a
week at induction of
therapy then once
weekly thereafter32
Acyclovir Once Once
Foscarnet Once Two to three times
Electrolytes +
calcium and
magnesium
Once


Cidofovir Once + prior to each
dose
Once + within 48
hours of each dose
Once: electrolytes
+ prior to each dose Once


a
Frequencies are minimal criteria for patients with normal or stable renal function. Different criteria may apply for children.
b
Clindamycin, pentamidine, and quinupristin/dalfopristin are not included due to low use in outpatient parenteral therapy. If necessary, refer to IDSA OPAT Guideline.
c
The electrolytes laboratory panel contains sodium, potassium, chloride, total carbon dioxide and anion gap. Calcium is included in the CMP; magnesium and phosphate are
ordered separately.
d
Liver enzyme function tests (include ALT, AST, alkaline phosphatase, and total bilirubin) are included in the CMP.
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

9
Antibiotic Agents
1.1. Aminoglycosides (gentamicin, tobramycin, amikacin)
1.1.1. Monitoring of once weekly CBC and twice weekly creatinine/BUN is
recommended for aminoglycosides (Class I, Level B)4
1.1.2. Drug concentration monitoring
1.1.2.1. Traditional and synergy dosing
1.1.2.1.1. Aminoglycoside concentration monitoring should occur after
five half-lives for synergy and traditional dosing (Class IIa,
Level B)5
1.1.2.1.2. Trough drug concentrations should be monitored at least
once weekly during prolonged therapy using traditional or
synergy dosing (Class I, Level A)5
1.1.2.2. Extended interval dosing
1.1.2.2.1. A single drug concentration should be obtained between 6
and 14 hours after the start of the 60 minute aminoglycoside
infusion. This drug concentration should be used with the
appropriate nomogram to determine the interval for
subsequent doses (Class I, Level A)6
1.1.2.2.2. After the dosing frequency is determined, trough
concentrations should be drawn 30-60 minutes before the
dose and can be used to monitor for nephrotoxicity and drug
accumulation (Class I, Level A)6
1.1.2.3. Drug concentration monitoring varies depending on therapy (traditional,
extended-interval dosing, or synergy). Refer to the ³UWHC Guidelines
for the Pharmacokinetic/Pharmacodynamic Dose Optimization of
$QWLELRWLFV��ȕ-lactams, aminoglycosides, and ciprofloxacin) for the
Treatment of Gram-1HJDWLYH�,QIHFWLRQV�LQ�$GXOWV´ for more information
regarding aminoglycoside concentration monitoring.
1.2. Beta lactams (penicillins, cephalosporins, aztreonam, carbapenems, piperacillin-
tazobactam)
1.2.1. Monitoring of once weekly CBC with differential and once weekly creatinine/BUN
is reasonable for beta-lactams (Class IIa, Level B)7-11
1.2.2. When administering nafcillin, oxacillin, and carbapenems, it is reasonable to
monitor liver enzymes once weekly (Class IIa, Level B)7-10
1.2.3. When administering ceftaroline, monitor for signs and symptoms of hemolytic
anemia during and after treatment. If anemia develops, perform diagnostic
VWXGLHV�LQFOXGLQJ�D�GLUHFW�&RRPE¶V�WHVW�(Class I, Level B)12
1.3. Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)
1.3.1. Monitoring of once weekly CBC with differential, creatinine/BUN, and liver
enzymes is reasonable for fluoroquinolones (Class IIa, Level B)13
1.4. Daptomycin
1.4.1. Monitoring of once weekly CBC with differential, creatinine/BUN, and liver
enzymes is reasonable for daptomycin (Class IIa, Level B)14
1.4.2. Monitoring of creatine phosphokinase (CPK) levels is indicated weekly, and more
frequently in patients who received recent prior or concomitant therapy with a
statin or in whom elevations in CPK occur during treatment with daptomycin
(Class I, Level A)14
1.4.2.1. If elevated CPK or myopathy occurs, consider discontinuation of
daptomycin
1.4.3. In patients with renal impairment, both creatinine/BUN and CPK should be
monitored more frequently than once weekly (Class I, Level A)14
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

10
1.5. Linezolid
1.5.1. Monitoring of once weekly CBC with differential is recommended for linezolid
(Class I, Level A)15
1.6. Trimethoprim-sulfamethoxazole (high dose, >10 mg/kg based on TMP component)
1.6.1. Monitoring of weekly CBC with differential, creatinine/BUN, and electrolytes
(particularly potassium) is reasonable for trimethoprim-sulfamethoxazole (Class
IIa, Level B)16
1.7. Glycopeptides (vancomycin, dalbavancin, oritavancin)
1.7.1. Once weekly CBC with differential and creatinine/BUN is reasonable for
vancomycin, dalbavancin, and oritavancin (Class IIa, Level B)17-19
1.7.2. Trough vancomycin concentrations are the most accurate and practical method
for monitoring vancomycin effectiveness (Class IIa, Level B)20
1.7.2.1. Recommend monitoring weekly trough concentrations for all patients
receiving prolonged courses of vancomycin
1.7.2.2. More than weekly monitoring of trough vancomycin concentrations to
reduce nephrotoxicity is recommended for patients with unstable renal
function, for elderly patients, for those receiving aggressive dosing
targeted to produce sustained trough drug concentrations of 15±20
mg/L, and for those who are at high risk of toxicity, such as patients
receiving concurrent nephrotoxins
1.7.2.3. Frequent monitoring (more than a single trough concentration before the
fourth dose) for short-course therapy (less than five days) or for lower-
intensity dosing (targeted to attain trough vancomycin concentrations
below 15 mg/L) is not recommended

Antifungals
1.0. Amphotericin B (including lipid formulations)
1.0.1. Monitoring of weekly CBC with differential, twice weekly creatinine/BUN, twice
weekly electrolytes and magnesium, once weekly liver enzymes is reasonable for
amphotericin B (Class IIa, Level B)21
1.1. Azole antifungal agents (fluconazole, voriconazole, itraconazole, posaconazole,
isavuconazole)
1.1.1. Monitoring of weekly CBC with differential, weekly creatinine/BUN, and weekly
liver enzymes is reasonable for azole antifungals (Class IIa, Level B)22-25
1.1.1.1. Fluconazole and itraconazole liver enzymes tests may be monitored
monthly if normal at baseline, and voriconazole and posaconazole
biweekly or monthly once a stable pattern is identified3
1.1.1.2. Monitoring parameters and frequency have not been established for
isavuconazole26
1.1.2. Steady state drug concentration levels should be considered after prophylaxis or
therapy initiation, dose changes, or patient condition changes for voriconazole,
itraconazole, and posaconazole.27,28 5HIHU�WR�WKH�³UWHC Guidelines for
$QWLIXQJDO�$JHQWV�LQ�$GXOWV´�IRU�PRUH�LQIRUPDWLRQ�
1.2. Echinocandins (caspofungin, micafungin, anidulafungin)
1.2.1. Monitoring of once weekly CBC with differential, electrolytes (particularly
potassium) and liver enzymes is reasonable for echinocandins (Class IIa, Level
B)29,30
1.2.1.1. Once steady state has been established, liver enzymes can be
monitored biweekly or monthly

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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

11
Antivirals
1.0. Ganciclovir
1.0.1. Monitoring of twice weekly CBC with differential, creatinine/BUN, and electrolytes
is recommended during induction of ganciclovir therapy and once a week
thereafter (Class I, Level A)31,32
1.1. Acyclovir
1.1.1. Monitoring of once weekly CBC with differential and creatinine/BUN is
reasonable for acyclovir (Class IIa, Level B)33
1.2. Foscarnet
1.2.1. Monitoring of once weekly CBC with differential and liver enzyme tests is
recommended for foscarnet (Class I, Level A)34
1.2.2. It is recommended to monitor renal function tests two to three times weekly
during induction of therapy and at least every one to two weeks during
maintenance. More frequent monitoring may be required for patients with renal
impairment. It is also recommended that a 24-hour creatinine clearance be
determined at baseline and periodically thereafter to ensure correct dosing
(Class I, Level A)31
1.2.3. It is recommended to monitor electrolytes, calcium, and magnesium two to three
times weekly during induction of therapy and at least every one to two weeks
during maintenance (Class I, Level A)31,34
1.3. Cidofovir
1.3.1. Monitoring of once weekly CBC with differential, creatinine/BUN, and
electrolytes, calcium, and magnesium is recommended for cidofovir (Class IIa,
Level B)35
1.3.1.1. Monitoring of these parameters is recommended within 48 hours prior of
each dose
1.3.2. Cidofovir should be used with caution in patients with renal dysfunction or
significant proteinuria is detected and if patient is receiving concomitant
nephrotoxic agents (Class I, Level A)31,35

C. Companion/Collateral documents
IDSA Outpatient Parenteral Antimicrobial Therapy (OPAT) Guideline

D. Potential Benefits
Standardization of OPAT laboratory ordering

E. Potential Harms
OPAT adverse drug events due to lack of individualization for patients that may require more
frequent laboratory monitoring or additional tests.

F. Qualifying Statements
Recommendations presented are mostly based on expert opinion given that frequency of
laboratory monitoring is not well established through evidence-based literature.

G. Implementation Plan and Tools
This guideline will be available as a reference link in the OPAT section of the Discharge
Navigator in Healthlink available to inpatient clinical pharmacists responsible for medication
discharge instructions. Education on this guideline will be distributed to pharmacists through a
computer-based training on modifications of OPAT inpatient management. This guideline will
also be available electronically through UConnect.

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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

12

Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and
treatment of patients. This Clinical Practice Guideline outlines the preferred approach for most
SDWLHQWV���,W�LV�QRW�LQWHQGHG�WR�UHSODFH�D�FOLQLFLDQ¶V�MXGJPent or to establish a protocol for all
patients. It is understood that some patients will not fit the clinical condition contemplated by a
guideline and that a guideline will rarely establish the only appropriate approach to a problem.

H. References
1. Tricoci P, Allen J, Kramer J, Califf R, Smith S. Scientific evidence underlying the ACC/AHA Clinical
Practice Guidelines. JAMA. 2009;301(8):831-841.
2. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial
therapy. IDSA guidelines. Clin Infect Dis. 2004;38(12):1651-1672.
3. Pietruszka, MH. UW Guidelines for Laboratory Monitoring of Outpatient Parenteral Antimicrobial
Therapy (OPAT). Approved December 2009.
4. Williams DN, Rehm SJ, Tice AD, Bradley JS, Kind AC, Craig WA. Practice guidelines for community-
based parenteral anti-infective therapy. Clin Infect Dis. 1997;25:787±801.
5. Bauer LA. Applied clinical pharmacokinetics. 2nd ed. New York: McGraw-Hill Medical; 2008.
6. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a
once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents
Chemother. 1995;39:650±655.
7. Product Information: nafcillin sodium injection, nafcillin sodium injection. Baxter Healthcare
Corporation, Deerfield, IL, 2011.
8. Product Information: oxacillin sodium intramuscular, intravenous injection, oxacillin sodium. Sagent
Pharmaceuticals, Schaumberg, IL, 2013.
9. Product Information: Invanz(R), ertapenem for injection. Merck & Co, Whitehouse Station, NJ, 2014.
10. Product Information: MERREM(R) IV injection, meropenem IV injection. AstraZeneca
Pharmaceuticals LP, Wilmington, DE, 2013.
11. Product Information: ZOSYN(R) IV injection, piperacillin and tazobactam IV injection. Wyeth
Pharmaceuticals Inc., Philadelphia, PA, 2013.
12. Product Information: TEFLARO(TM) IV injection, ceftaroline fosamil IV injection. Forest
Pharmaceuticals, Inc, St Louis, MO, 2013.
13. Product Information: LEVAQUIN(R) multiple routes, forms, levofloxacin multiple routes, forms.
Janssen Pharmaceuticals, Inc. (Per FDA), Titusville, NJ, 2012.
14. Product Information: CUBICIN(R) IV injection, daptomycin IV injection. Cubist Pharmaceuticals,Inc,
Lexington, MA, 2014.
15. Product Information: ZYVOX(R) injection, tablets, oral suspension, linezolid injection, tablets, oral
suspension. Pharmacia & Upjohn, New York, NY, 2014.
16. Product Information: BACTRIM(TM) double strength oral tablets, oral tablets, sulfamethoxazole and
trimethoprim DS double strength oral tablets, oral tablets. AR Scientific, Inc. (per FDA), Philadelphia,
PA, 2012.
17. Product Information: vancomycin IV injection, vancomycin IV injection. Baxter Healthcare
Corporation, Deerfield, IL, 2014.
18. Product Information: DALVANCE(TM) intravenous injection, dalbavancin intravenous injection.
Durata Therapeutics, Inc. (per manufacturer), Chicago, IL, 2014.
19. Product Information: ORBACTIV(TM) intravenous injection lyophilized powder, oritavancin
intravenous injection lyophilized powder. The Medicines Company (per manufacturer), Parsippany,
NJ, 2014.
20. 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(1):82-98.
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

13
21. Product Information: amphotericin B intravenous injection lyophilized powder for solution,
amphotericin B intravenous injection lyophilized powder for solution. X-Gen Pharmaceuticals, Inc.
(per DailyMed), Big Flats, NY, 2011.
22. Product Information: DIFLUCAN(R) oral tablet, intravenous solution, oral suspension, fluconazole oral
tablet, intravenous solution, oral suspension. Pfizer Roerig, New York, NY, 2014.
23. Product Information: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral
tablets, oral suspension, intravenous injection. Pfizer Roerig (per FDA), New York, NY, 2014.
24. Product Information: Noxafil(R) oral delayed-release tablets, oral suspension, intravenous injection,
posaconazole oral delayed-release tablets, oral suspension, intravenous injection. Merck Sharp &
Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2014.
25. Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen
Pharmaceuticals, Inc. (per FDA), Titusville, NJ, 2014.
26. Schmitt-hoffmann A, Roos B, Maares J, et al. Multiple-dose pharmacokinetics and safety of the new
antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug,
BAL8557, in healthy volunteers. Antimicrob Agents Chemother. 2006;50(1):286-293.
27. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging
indications. Antimicrob Agents Chemother. Jan 2009;53(1):24-34.
28. Smith J, Andes D. Therapeutic drug monitoring of antifungals: pharmacokinetic and
pharmacodynamic considerations. Ther Drug Monit. Apr 2008;30(2):167-172.
29. Product Information: CANCIDAS(TM) IV injection, caspofungin acetate IV injection. Merck and Co
Inc, Whitehouse Station, NJ, 2014
30. 3URGXFW�,QIRUPDWLRQ��0\FDPLQHŒ��PLFDIXQJLQ��$VWHOODV�3KDUPD�86��,QF��1RUWKEURRN��,/�������
31. Kaplan JE , Benson C , Holmes KH , et al: Guidelines for prevention and treatment of opportunistic
infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes
of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR
Recomm Rep. 2009;58(RR-4):1-207.
32. Product Information: CYTOVENE-IV(R) IV injection, ganciclovir sodium IV injection. Roche
Laboratories Inc, Nutley, NJ, 2010.
33. Product Information: acyclovir oral capsules, oral tablets, acyclovir oral capsules, oral tablets. Mylan
Pharmaceuticals Inc. (per DailyMed), Morgantown, WV, 2012.
34. Product Information: FOSCAVIR(R) IV injection, foscarnet sodium IV injection. AstraZeneca, Lake
Forest, IL, 2007.
35. Product Information: VISTIDE(R) IV injection, cidofovir IV injection. Gilead Sciences, Inc, Foster City,
CA, 2010.


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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

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Clinical Monitoring of Outpatient Parenteral Antimicrobial Therapy
(OPAT) and Selected Oral Antimicrobial Agents – Adult –
Inpatient/Ambulatory – Clinical Practice Guideline

Appendix A. Coordinating an OPAT Discharge

From: Clinical Monitoring of Outpatient Parenteral Antimicrobial Therapy (OPAT) and
Selected Oral Antimicrobial Agents ± Adult ± Inpatient/Ambulatory ± Clinical Practice
Guideline
CPG Contact for Content: Lucas Schulz, PharmD, BCPS (AQ-ID); 608-890-8617;
lschulz2@uwhealth.org

OPAT discharge navigator and laboratory monitoring
ξ Select OPAT button for ALL patients that discharge on intravenous antimicrobials



ξ Confirm team has ordered appropriate labs
o Labs should appear in the OPAT monitoring navigator if they are ordered through UWHealth. If
ordered outside of UWHealth, labs will not appear in this section and confirmation of ordering will
need to be made by discussion with primary team.


ξ Compare ordered labs to OPAT Guideline and ID consult note (if available)
ξ Ask team to order any missing labs (lab ordering is the responsibility of the provider)
ξ Confirm date for first outpatient drug level (if necessary) by communicating with infusion agency
o Some Home Health nurses can only draw labs on certain days; discuss with infusion agency to
confirm most appropriate time for first outpatient drug level
ξ 6HOHFW�³ODERUDWRU\�PRQLWRULQJ�KDV�EHHQ�UHYLHZHG´�EXWWRQ�LQ�+HDOWK/LQN
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UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

15
Preparing OPAT prescriptions
ξ Ensure team orders drug for injection on discharge
o Discharge Navigator  Order Reconciliation  New Med Orders for Discharge tab  Database
lookup




o Do NOT order the drug in a base fluid. The infusion agency will put the drug in the most
appropriate fluid and concentration for home stability when the infusion agency pharmacists
receive the prescription.
ξ Round dose to nearest 10 mg for daptomycin
ξ &KDQJH�GLVSHQVH�TXDQWLW\�WR�³��HDFK´
ξ &KDQJH�UHILOOV�WR�³351´�HYHQ�LI�GXUDWLRQ�LV�NQRZQ�
o This allows the infusion agency to re-dispense drug if patients have storage issues or
malfunctions while dispensing at home
ξ If duration is known, add anticipated stop date as a note in Discharge Medication List and discharge
hand-off note
ξ Print prescription for fax; fax to infusion agency
ξ Include the name of the provider who will follow the patient after discharge in the discharge hand-off
note

Contacting Home Infusion Agency
ξ Look at social work or Chartwell note in HealthLink for fax numbers, contact information, or planning
information
ξ Chartwell nurses are available during business hours at UW University Hospital
ξ Chartwell main office: 608-831-8555
o Can speak to pharmacist during business hours for drug or dosing questions
o Can ask to speak with on-call pharmacist after-hours or on weekends
ξ Paging (2-2122 or 262-2122) can assist in contacting a home infusion agency

Clinical considerations for home infusions
(All recommendations: UW Health Strong Recommendation, Moderate Quality of Evidence)

ξ Try to avoid checking inpatient drug troughs on the day of discharge if possible
o Infusion agencies process orders and prepare the first home dose the morning of discharge;
pending troughs will delay care
ξ It is preferred to administer drugs at home over short infusions or IV push to significantly decrease
amount of time patient is connected to pump
o Improves ability to fit into work/life/sleep schedule
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org

UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

16
o Enhances adherence
o All antimicrobials can be administered via Rateflow short infusion (small-volume admixture
connected to IV pole) EXCEPT nafcillin/oxacillin and penicillin G
o The following antimicrobials can be administered via IV push or Freedom 60 pump by Chartwell
(other home infusion agencies may have different practices), avoiding the need to be connected
to an IV pole:
Amikacin** Ceftazidime Meropenem*
Aztreonam Ceftriaxone Nafcillin *
Cefazolin* Cefuroxime Oxacillin *
Cefepime* Clindamycin** Piperacillin-tazobactam *
Cefotaxime Daptomycin Tobramycin**
Cefotetan Gentamicin** Vancomycin***
Cefoxitin
* IV push available, however, prolonged infusion is the preferred method of administration
** 30-60 minute infusion on Freedom 60 pump, no IV push available
*** 60-90 minute infusion on Freedom 60 pump, no IV push available

ξ Factors that prohibit short infusions or IV push antibiotics with OPAT may include (but are not limited
to):
o Accepting facility or patient family unable to perform multiple administrations daily
o Patient inability to complete short infusion or IV push independently
o Therapeutic inferiority with short infusion (i.e. therapeutic superiority with prolonged infusion or
continuous infusion)
ξ The following antimicrobials have frequent dosing intervals and can therefore be made in a 24-hour
bag by Chartwell (other home infusion agencies may have different practices), which can be given as
continuous infusion or programmed on a pump that fires intermittent doses from the same bag:
Acyclovir Cefotetan Ceftolozane-tazobactam *
Ampicillin Cefoxitin Meropenem **
Aztreonam Ceftazidime Nafcillin *
Cefazolin Cefuroxime Oxacillin *
Cefepime Clindamycin Penicillin G potassium *
Cefotaxime Doripenem Piperacillin-tazobactam *
Vancomycin
* Continuous infusion is the preferred method of administration
** Must change bag after 12 hours instead of 24 hours

ξ Ampicillin-sulbactam does not have good home stability and cannot be given as a 24-hour bag
o Patients or caregivers have to be willing and able to administer this medication multiple times a
day
ξ Some SNFs or Home Health agencies cannot run extended infusions, cannot administer medications
every 6 hours, and/or cannot hook patients up to 24-hour pumps
o This is rare, but can create difficulty if it occurs. Attempt to confirm this before discharge day.
o The dosing for extended beta-lactam infusions and intermittent/short infusions may be different.
See the Renal Function-Based Dose Adjustments Clinical Practice Guideline and the
Pharmacokinetic/Pharmacodynamic Dose Optimization of Antibiotics for the Treatment of Gram-
negative Infections Clinical Practice Guidelines
ξ If antimicrobial infusion cost is preventing discharge to home or to other facility, work with attending
team and/or Infectious Disease service to identify if other antimicrobial choices may facilitate discharge


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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org

UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

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Antimicrobial Drug for Injection Medication Record Numbers (ERx)
Antimicrobial ERx for OPAT Injection Database Lookup (F7) Concentrations or Strengths
Liposomal amphotericin 58058 50 mg
Acyclovir 44030 500 mg
Amikacin 760007 250 mg/mL
Ampicillin 34543 1 g
34546 2 g
Ampicillin-sulbactam 50601 1.5 g
50599 3 g
Azithromycin 57146 500 mg
Aztreonam 44264 1 g
44265 2 g
Caspofungin 66233 50 mg
66234 70 mg
Cefazolin 35636 1 g
Cefepime 52161 1 g
52163 2 g
Cefoxitin 44555 1 g
44557 2 g
Ceftazidime
44571 500 mg
44568 1 g
44570 2 g
Ceftriaxone 44581 1 g
44582 2 g
Cefuroxime 35657 750 mg
35655 1.5 g
Ciprofloxacin 144939 200 mg/ 20 mL
144940 400 mg/ 40 mL
Clindamycin
119041 300 mg/ 2 mL
119039 600 mg/ 4 mL
119040 900 mg/ 6 mL
Daptomycin 73977 500 mg
Doripenem 143475 250 mg
126526 500 mg
Ertapenem 68678 1 g
Ganciclovir 45226 500 mg
Gentamicin 37859 10 mg/mL
37860 40 mg/mL
Levofloxacin 54892 25 mg/mL
Linezolid
170913 200 mg/ 100 mL
170914 600 mg/ 300 mL
Meropenem 53238 500 mg
53239 1 g
Micafungin 107268 50 mg
115014 100 mg
Nafcillin
39988 1 g
39990 2 g
39989 10 g
Oxacillin
40651 1 g
40653 2 g
40652 10 g
Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org

UWHC Clinical Monitoring for OPAT and Selected Oral Antimicrobial Agents CPG

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Antimicrobial ERx for OPAT Injection Database Lookup (F7) Concentrations or Strengths
Penicillin G Potassium 40825 5,000,000 units
40824 20,000,000 units
Penicillin G Sodium 40826 5,000,000 units
Piperacillin-tazobactam
54253 2.25 g
54252 3.375 g
54251 4.5 g
Rifampin 46481 600 mg
Sulfamethoxazole-
trimethoprim 42456 400-80 mg/ 5 mL
Tigecycline 107987 50 mg
Tobramycin 760239 40 mg/mL
104635 80 mg/ 2 mL
Vancomycin
43437 500 mg
135474 750 mg
43436 1000 mg
Voriconazole 69968 200 mg

Copyright © 201� University of Wisconsin Hospital s and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2016CCKM@uwhealth.org