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Non-Thoracic Solid Organ Transplant Rejection Antimicrobial Prophylaxis – Adult – Ambulatory [76]

Non-Thoracic Solid Organ Transplant Rejection Antimicrobial Prophylaxis – Adult – Ambulatory [76] - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Delegation/Practice Protocols, Ambulatory Delegation Protocols





Delegation Protocol Number: 76

Delegation Protocol Title:
Non-Thoracic Solid Organ Transplant Rejection Antimicrobial Prophylaxis - Adult - Ambulatory

Delegation Protocol Applies To:
Adult patients seen in the Transplant Clinic

Target Patient Population:
Adult patients who have received a non-thoracic solid organ transplant (kidney, liver, pancreas or any
combination thereof) and who are actively undergoing treatment with steroids for rejection of the
transplant.

Delegation Protocol Champions:
Didier Mandelbrot, MD - Department of Surgery, Division of Transplant Surgery
John Rice, MD - Department of Surgery, Division of Transplant Surgery

Delegation Protocol Reviewers:
Jillian Fose, PharmD - Pharmacy
Margaret Jorgenson, PharmD - Pharmacy

Responsible Department:
Department of Pharmacy

Purpose Statement:
To delegate authority from providers in the Transplant Clinic to clinical pharmacists and transplant
coordinators to determine and order the appropriate antimicrobial prophylaxis for non-thoracic solid
organ transplant patients receiving treatment with intravenous or oral steroids for rejection in the
outpatient setting

Who May Carry Out This Delegation Protocol:
Clinical pharmacists and transplant coordinators in the Transplant Clinic who are trained in the use of this delegation
protocol.

Guidelines for Implementation:
1. This delegation protocol is initiated when a provider identifies a patient with rejection of a non-
thoracic solid organ transplant and prescribes either intravenous or oral corticosteroids at a dose
equivalent to dexamethasone 20 mg or greater. The provider notifies the clinic nurse or transplant
coordinator that the patient is being treated for rejection with corticosteroids.
2. The clinic nurse enters a “Note” order in Health Link to notify Pharmacy that the patient is being
treated for rejection. The order will be entered as an Inpatient. The order will appear in the
pharmacist’s verification queue.
3. Using Health Link, the clinical pharmacist will review the patient’s allergies, past medication list and
most recent creatinine clearance estimate to determine drug selection and dosing. The pharmacist
will then use Tables 1, 2, 3, and 4 to determine the appropriate antiviral, antibacterial, and
antifungal prophylactic therapy. The pharmacist will enter orders for these medications in Health
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org

Link. With the exception of pentamidine and albuterol, the prescriptions may be e-prescribed to
the patient’s preferred pharmacy or a paper prescription may be given to the patient.
Prescriptions for pentamidine and albuterol will be printed and a paper copy provided to the
patient along with information on how to arrange appointments with a respiratory therapy
department of the patient’s choosing.
4. Selection of therapy
4.1. Antiviral therapy
4.1.1. Antiviral prophylaxis will be prescribed at the time the treatment for rejection based on
the donor and recipient CMV (cytomegalovirus) status at the time of transplant, history
of CMV infection, as well as the agent being used for treatment of the rejection (Table
1). Of note: in the case of CMV D-/R- at time of transplant CMV IGG should be repeated
to rule out seroconversion

Table 1. Selection of antiviral agent
CMV Status Antiviral Agent
D+ or R+ or history of CMV Valganciclovir
D-/R- and no history of CMV Acyclovir x 1 month

4.1.2. Duration of valganciclovir will vary based on treatment agent and patient history of
CMV. If the patient is receiving additional rejection therapies (thymoglobulin,
rituximab, bortezomib) or has history of CMV then the duration will be 3 months. If
the patient is only receiving steroids and has no history of CMV the duration will be
one month.
4.1.3. If the patient is currently on valganciclovir prophylaxis as an outpatient, it will be
continued for an additional 1-3 months from the time the treatment for rejection
occurred. If the patient qualifies for valganciclovir it will be dosed per Table 2.

Table 2. Antiviral Prophylaxis – Valganciclovir
Creatinine Clearance Oral Valganciclovir Dose
>60 mL/min 900 mg daily
40-59 mL/min 450 mg daily
25-39 mL/min 450 mg every other day
< 25 mL/min 450 mg twice a week after hemodialysis

4.1.4. If patients cannot afford prophylactic valganciclovir, or those who develop neutropenia
(ANC < 500/mm3) should receive pre-emptive monitoring with weekly CMV PCR.
Reduced doses of valganciclovir in the setting of good renal function have been
associated with the development of ganciclovir resistance

4.1.5. Acyclovir will be dosed per Table 3.
Table 3. Antiviral Prophylaxis - Acyclovir
Creatinine Clearance Oral Acyclovir Dose
≥ 10 mL/min 400 mg PO BID
<10 mL/min or HD 200 mg PO BID

Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org

4.2. Antibacterial therapy to prevent pneumocystis jiroveci pneumonia (PJP)
4.2.1. Trimethoprim/sulfamethoxazole (TMP/Sulfa) will be prescribed for 3 months from
the time the treatment for rejection occurred based on the prophylactic dosing in
Table 4.

Table 4. Antibacterial Prophylaxis – TMP/Sulfa
Criteria Oral TMP/Sulfa Dose
CrCl > 30 mL/min 160/800 mg daily
CrCl <30 mL/min 160/800 mg every other day
On hemodialysis
160/800 mg 3 times per week given after
hemodialysis
Hyperkalemia
(K > 4.8 mmol/L)
160/800 mg every Monday, Wednesday,
and Friday

4.2.2. If the patient has a histamine-mediated allergic reaction to sulfa or other
contraindication, the alternative agent of choice is atovaquone. Please see Table
5 for dosing and other alternatives Table 5.

Table 5. Antibacterial Prophylaxis – TMP/Sulfa Intolerance
Drug Dose Comments
Atovaquone 1500 mg daily Test claim for insurance
coverage
Also provides toxoplasmosis
coverage
Dapsone 100 mg daily Screen for G6PD deficiency
Pentamidine 300 mg inhalation per nebulization Pretreat with 2.5 mg of
inhaled albuterol per
nebulization
4.3. Antifungal therapy to prevent oral candidasis
4.3.1. Nystatin will be prescribed for 1 month from the time the treatment for
rejection occurred.
4.3.2. If the patient is currently on clotrimazole or nystatin it will be continued for an
additional 1 month from the time the treatment for rejection occurred. If the
patient’s insurance does not cover nystatin or the patient does not tolerate the
taste of nystatin, clotrimazole will be ordered.

Table 6. Antifungal Prophylaxis
Agent Oral Dose
Clotrimazole troche 10 mg twice daily
Nystatin suspension 100,000 unit/mL 5 mL twice daily

5. The pharmacist will enter a note in Health Link indicating antiviral, antibacterial, and
antifungal prophylaxis therapy has been prescribed per protocol. The clinical pharmacist
will document the rejection treatment agent and prophylactic regimen selected. After
completed, the pharmacist will route the note in Health Link to the patient’s transplant
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org

coordinator.
6. This protocol may be overridden at any time by an order for any of the prophylactic agents
indicating “dispense as written” or similar designation in the administration instructions
within the order.

Order Mode: Protocol/Policy, Without Cosign

References:
1. Fletcher C, Chinnock B, Chace B, Balfour HJ. Pharmacokinetics and safety of high-dose oral
acyclovir for suppression of cytomegalovirus disease after renal transplantation. Clin Pharmacol
Ther. Aug 1988;44(2):158-163.
2. Martin M, Mañez R, Linden P, et al. A prospective randomized trial comparing sequential
ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease
in adult liver transplant recipients. Transplantation. Oct 1994;58(7):779-785.
3. Cytomegalovirus. Am J Transplant. Nov 2004;4 Suppl 10:51-58.
4. Razonable R. Cytomegalovirus infection after liver transplantation: current concepts and
challenges. World J Gastroenterol. Aug 2008;14(31):4849-4860.
5. Cochrane A. Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid
organ transplant recipients. Am J Health Syst Pharm. Oct 2006;63(19 Suppl 5):S17-
21.Kletzmayr J, Kotzmann H, Popow-Kraupp T, Kovarik J, Klauser R. Impact of high-dose oral
acyclovir prophylaxis on cytomegalovirus (CMV) disease in CMV high-risk renal transplant
recipients. J Am Soc Nephrol. Feb 1996;7(2):325-330.
6. Flechner S, Avery R, Fisher R, et al. A randomized prospective controlled trial of oral
acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney
transplant recipients. Transplantation. Dec 1998;66(12):1682-1688.
7. Fletcher C, Englund J, Edelman C, Gross C, Dunn D, Balfour HJ. Pharmacologic basis for high-
dose oral acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients.
Antimicrob Agents Chemother. May 1991;35(5):938-943.
8. Bertoni E, Rosati A, Zanazzi M, et al. Cytomegalovirus disease prophylaxis in renal
transplantation by high dose oral acyclovir: efficacy and limits. Transplant Proc. Aug
1998;30(5):2094.
9. Winston D, Busuttil R. Randomized controlled trial of oral ganciclovir versus oral acyclovir
after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus
disease in cytomegalovirus-seropositive liver transplant recipients. Transplantation. Jan
2003;75(2):229-233.
10. Winston D, Wirin D, Shaked A, Busuttil R. Randomised comparison of ganciclovir and high-
dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients.
Lancet. Jul 1995;346(8967):69-74.
11. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical
practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl
3):S1-S157.
12. Fishman JA. Prevention of infection caused by pneumocystis carinii in transplant
recipients. Clin Infect DisI. 2001;33(8):1397-1405.
13. Rodriguez M, Fishman JA. Prevention of infection due to pneumocystis spp. in human
immunodeficiency virus-negative immunocompromised patients. Clin Microbiol Rev.
2004;17(4):770 - 782.
14. Fox BC, Sollinger HW, Belzer FO et al. A prospective, randomized, double-blind study of
trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation, effects on
the microflora, and the cost-benefit of prophylaxis. Am J Med. 1990;89:255- 274.
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org

15. Perazella MA. Trimethoprim-induced hyperkalemia: clinical data, mechanism, prevention and
management. Drug Saf. 2000;22(3):227-236
16. Gombert ME, duBouchet L, Aulicino TM, et al. A comparative trial of clotrimazole
trouches and oral nystatin suspension in recipients of renal transplants: use in
prophylaxis of oropharyngeal candidiasis. JAMA. 1987;258:2553-2555
17. Reents S, Goodwin SD, Singh V. Antifungal prophylaxis in immunocompromised hosts.
Ann Pharmacother. 1993;27(1):53-60
18. Owens NJ, Nightingale CH, Schweizer RT, et al. Prophylaxis of oral candidiasis with
clotrimazole trouches. Arch Intern Med. 1984;144(2):290-293

Collateral Documents/Tools:
1. UW Health Renal Function-Based Dose Adjustments – Adult – Inpatient/Ambulatory Clinical
Practice Guideline. Accessed August 2017.

Approved By:
UW Health Ambulatory Protocol Committee: November 2017
UW Health Antimicrobial Use Subcommittee: November 2017
UWHC Pharmacy & Therapeutics Committee: November 2017
UW Health Medical Board: November 2017
UW Health Chief Medical Officer: November 2017

Effective Date: November 2017

Scheduled for Review: November 2020


Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org