Liver Transplant Surgery - Guideline for Antimicrobial Prophylaxis for

Publication: 01/03/2010  
Last review: 15/03/2016  
Next review: 15/09/2019  
Clinical Guideline
UNDER REVIEW 
ID: 1824 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2016  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for Antimicrobial Prophylaxis for Liver Transplant Surgery

1. Summary of routine recommendations
2. Background information
3. Special antimicrobial prophylaxis recommendations

1. Summary of routine recommendations

Below is a summary of routine recommendations:

1. General screening recommendations
2. Pre- and peri-operative MRSA prophylaxis
3. Table for antibiotic and antifungal surgical prophylaxis
4. Post-transplant prophylaxis against CMV, PCP and TB infections

It is essential to use all 3 sections of this guidance, as the table only covers the antibiotic and anti-fungal component. The MRSA guidance is contained in section 2.

Procedure

Prophylaxis recommended?

Evidence level

Prophylaxis aims to reduce

NNT

Antimicrobial dose/route start at <1 hours before procedure

Routine

True penicillin allergy

Liver transplant:
first procedure - elective
(includes top band and prioritised patients)

Yes

D

SSI

 

 

MRSA

N/K

Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclav 1.2g IV 8-hourly for 24 hours
Re-dose every 2 hours peri-operatively.

 

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg IV 12-hourly + Metronidazole electronic Medicines Compendium information on Metronidazole 500mg IV 8-hourly for 24 hours

 

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

 

Yes

B

Invasive Fungal Infection

14

Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily for 7 days.

See below for prolonged ICU stay advice

Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily for 7 days.

See below for prolonged ICU stay advice

Liver transplant:
first transplant - emergency
(supra-urgent)

Yes

D

SSI

 

 
MRSA

N/K

Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g IV 8-hourly for up to 5 days (review at 48 hours).

 

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg IV 12-hourly + Metronidazole electronic Medicines Compendium information on Metronidazole 500mg IV 8-hourly for up to 5 days (review at 48 hours).

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

 

 

Yes

 

B

Invasive Fungal Infection

 

6

Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily for 7 days

See below for prolonged ICU stay advice

Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily for 7 days

See below for prolonged ICU stay advice

Liver transplant:
-regraft

(superurgent or elective)

Yes

D

SSI

 

 
MRSA

N/K

Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g IV 8-hourly for up to 5 days (review at 48 hours).

 

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg IV 12-hourly + Metronidazole electronic Medicines Compendium information on Metronidazole 500mg IV 8-hourly for up to 5 days reviewed daily.

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

 

Yes

B

Invasive Fungal Infection

6

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for 5 days post-op (Step down to Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily thereafter for 5 days)

 

See below for prolonged ICU stay advice

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for 5 days post-op (Step down to Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily thereafter for 5 days)

See below for prolonged ICU stay advice

Relaparotomy post-liver transplant
(within same admission; up to 3 months)

Yes

D

SSI

 

MRSA

N/K

Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g IV 8-hourly for 48 hours

 

Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg IV 12-h plus Metronidazole electronic Medicines Compendium information on Metronidazole 500mg IV 8-hourly for 48 hours


Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg IV single dose

 

Yes

B

Invasive Fungal Infection

6

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for 5 days post-op (Step down to Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily thereafter)

See below for prolonged ICU stay advice

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for 5 days post-op (Step down to Fluconazole electronic Medicines Compendium information on Fluconazole 200mg IV/PO/NG once-daily thereafter for 5 days)
See below for prolonged ICU stay advice

Prolonged ICU stay (>5 days post transplantation)

Yes

B

Invasive Fungal Infection

6

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for duration of ICU stay.

Ambisome electronic Medicines Compendium information on Ambisome 1mg/kg/day IV for duration of ICU stay.

N/K= not known

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1. General screening recommendations

Patients undergoing liver transplantation are at risk of infection both peri- and post-operatively, including opportunistic infection eg Cytomegalovirus and reactivation of latent infection eg Tuberculosis. Certain other infections can be worse in immunosuppressed individuals eg chicken pox. There is also increasing awareness of colonisation or exposure risk with multi-resistant organisms which may require special consideration when considering anti-microbial prophylaxis.

Patients on the liver transplant waiting list are therefore screened for:

  • Methicillin Resistant Staphlococcus Aureus (MRSA)
  • Carbapenamase Producing Enterobacteriaceae (CPE)
  • Previous Cytomegalovirus (CMV) infection (as part of liver transplant assessment)

Prophylaxis approaches for these are covered in the guidance below.

A new screening test for previous TB exposure has been added to the guidance below.

They are also screened for previous chicken pox (VZV), herpes simplex (HSV) and Epstein Barr virus (EBV) infection. This is not for prophylaxis purposes, but for general immunosuppression and post-transplant exposure management. These are not discussed further here.

2. MRSA Prophylaxis

All patients should be considered at high risk of MRSA colonisation/infection.
The aim of prophylaxis is to reduce the risk of surgical site infection.

2.1 Waiting list
All patients should continue to be screened for MRSA whilst on the waiting list at 3 monthly intervals.
If screen positive, decolonisation should be attempted whilst on the waiting list *.
Up to 2 attempts can be given, if remains positive please discuss with microbiology.

If a patient on the waiting list is admitted to the ward from another hospital, please follow the MRSA policy on the intranet

*If MRSA screen is positive check the MRSA is susceptible to mupirocin as the guidance above will need adaptation (as per the MRSA policy). Neomycin (naseptin) would normally be used in this setting but occasionally mupirocin resistant strains can be neomycin resistant too. Please see the MRSA Policy for further information in this setting.

2.2 On admission for transplant
All patients should receive:

  1. Mupirocin 2% cream applied to both nostrils 8-hourly for 5 days (unless screen positive with resistant strain, see above)
  2. Chlorhexidine 4% all-over body wash daily for 5 days (hair wash on two occasions during this time).
    Decolonisation should be started from the day/night of admission and continued through surgery and post-operatively for 5 days.

    This is for all patients regardless of screen status; the screening guidance above is to pick up screen positive patients and treat them ahead of call-in.

2.3 Peri-operatively
Perioperative IV Teicoplanin electronic Medicines Compendium information on Teicoplanin 400mg single dose

2.4 If the transplant does not go ahead
If feasible stop the decolonisation if the MRSA screen on admission is negative (to reduce risk of future mupirocin resistance).

3. Antibiotic and antifungal surgical prophylaxis
The following guidelines apply to bacterial and fungal infection prophylaxis. Please note they are guidelines for prevention of infection, not for treatment, and cannot cover every situation. If infection is suspected or develops despite prophylaxis, then treatment is needed, guided by the particular clinical presentation.

Similarly, where patients are already on antibiotics for treatment of an infection (suspected or confirmed), surgical prophylaxis may need to be reviewed. Please discuss with microbiology if unsure how to proceed.

3.1.1 Antibiotic prophylaxis: Resistant organisms
If patients are known to be colonised with resistant organisms (eg ESBLs, Carbapenemase Producing Enterobacteriaceae (CPEs), VRE), prophylaxis will need to be tailored to that individual. Patients on the liver transplant waiting list undergo routine screening for CPE. As a result of this carriage of other resistant organisms is being detected. If known in advance ie a patient screens positive whilst on waiting list or on the ward for CPE or other resistant organisms, surgical prophylaxis should be planned pre-transplant with advice from microbiology, and documented in the medical notes and on the transplant waiting list. This plan is communicated by the co-ordinators to the admitting doctor at the time of transplant admission and the advice is discussed with the on call microbiology StR on call to check the advice is still up to date and no new clinical information needs taking into account. This is particularly relevant to patients where a significant amount of time has elapsed between plan and transplant admission.

3.1.2 Antibiotic prophylaxis: Re-dosing
In the general surgical setting, guidelines recommend that antibiotics need to be re-dosed after 2 half-lives.
According to this recommendation Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclav and piperacillin-tazobactam which have short half-lives, would need re-dosing every 2 hours during the period of surgery. Potentially however this could involve additional volume and sodium loading, and may not be safe for liver transplant patients. Until further evidence becomes available therefore, we are not making a strong recommendation for this. However a re-dose should be considered with extremely prolonged surgery where a normal dosing interval would usually take place.  If there is renal dysfunction the pharmacists should be asked to review the dosing intervals after the first 24 hours. Teicoplanin electronic Medicines Compendium information on Teicoplanin, Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin and Metronidazole electronic Medicines Compendium information on Metronidazole have long half-lives and do not need re-dosing during surgery.

Re-dosing requirements for antibiotics not falling into the above list (ie individually tailored for resistant organisms) will require instructions from microbiology at time of transplant where possible; standard dosing intervals should otherwise apply.

3.2 Anti-fungal prophylaxis
Due to an alert from NHSBT regarding donor fungal infection transmission risk, these guidelines now incorporate anti-fungal prophylaxis for all transplant recipients.

For all first grafts Fluconazole electronic Medicines Compendium information on Fluconazole is first-line anti-fungal. For all second grafts, Ambisome electronic Medicines Compendium information on Ambisome is first-line anti-fungal. Invasive fungal infection (IFI) is most highly associated with the risk factors shown in box 1.

Box 1- Risk factors for IFI in Liver Transplant Recipients

  1. Fulminant liver failure (super-urgent transplants)
  2. Bilirubin >100 micromol/L
  3. Need for Renal replacement therapy (CVVH or HD) pre-, peri- or post-operatively.
  4. Prolonged ICU stay post -transplant (>5 days)
  5. Retransplantation
  6. Relaparotomy within 3 months of transplant
  7. Blood transfusion at operation ≥8units
  8. History of fungal infection/ colonisation.
  9. Evidence (clinical or microbiological) of oral, urethral or vaginal thrush.
  10. Retrieval surgery has included pancreas retrieval, or GI tract breached

4. Post-transplant prophylaxis for Pneumocystis, Cytomegalovirus and Tuberculosis

4.1 Pneumocystis jirovecii Pneumonia (PCP) Prophylaxis
Risk of PCP in liver transplant recipients is highest in periods of most intense immunosuppression, and is in the order of 5-15%.
The aim of prophylaxis is to reduce the risk of PCP infection.

All patients should therefore receive:

  1. Co-trimoxazole 480mg od from day 10 to day 100 post-transplant. The correct duration is issued by the pharmacists at discharge.
  2. For patients with Co-trimoxazole allergy/intolerance, alternative agents have significant side-effect profiles and limited additional coverage, so using an alternative is not routinely recommended. However very heavily immunosuppressed individuals e.g. those being treated for steroid resistant acute rejection with ATG, or patients with a past medical history of PCP, may benefit from an alternative agent in which case Dapsone 100mg od can be used.

Co-trimoxazole covers a range of organisms including toxoplasma, listeria and nocardia.

If co-trimoxazole is not being used, be mindful of the possibility of infection with the above, particularly in the event of known donor positive toxoplasma serology/active infection. Such cases should be discussed with microbiology. Maintain a high level of vigilance for PCP infection in the 3 month post-operative period.

4.2 Cytomegalovirus infection (CMV) prophylaxis
Risk of CMV infection post liver transplant is highest in periods of most intense immunosuppression and CMV-negative recipients (R-) receiving grafts from CMV positive donors (D+). Our unit refers to this scenario as “CMV mismatch”. Donor CMV status is communicated to the medical team by the transplant co-ordinators and is documented on PPM.

The aim of prophylaxis is to reduce primary CMV infection.

All D+/R- recipients should therefore receive:

  1. Valganciclovir 900mg od from day 10 to day 100 post-transplant (as per the SPC). The correct duration is issued by the pharmacists at discharge.
  2. Valganciclovir dosing needs to reduced in renal impairment (discuss with Liver Unit pharmacist if uncertain).

The risk of primary infection in CMV mismatch individuals persists following withdrawal of prophylaxis, particularly if immunosuppression remains high. Such patients should be screened at their clinic appointments via CMV-PCR testing until 12 months post-transplant. Monthly repeat testing is an appropriate minimum interval unless viraemia is being monitored.

4.3 Mycobacterium tuberculosis (TB) prophylaxis
Patients from high risk areas are at risk of TB reactivation. High risk areas are defined as countries where the incidence is 40 per 100 000 or higher and can be checked on www.gov.uk/government/publications/tuberculosis-tb-by-country-rates-per-100000-people.

The aim of prophylaxis is to prevent reactivation of latent TB.

Patients with a should be given prophylaxis with Isoniazid 300mg daily and Pyridoxine 10mg daily for 6 months post-transplant, starting as soon as possible and by day 10 at the latest.

Other patients may be at risk of reactivating latent TB. There is rising worldwide concern about multi-resistance to anti-tuberculous drugs. LTHT microbiologists therefore now recommend screening for evidence of previous TB exposure by means of a Quantiferon test. This can be ordered on the ICE system. Such patients can be screened if thought at risk in the pre-transplant clinic. Results are usually available within 3 working days.

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2. Background information

These guidelines were first produced following a meeting on 8th July 2009 attended by Dr Rebecca Jones and Dr Charles Millson, Transplant Hepatologists, Mrs Faye Croxen, Liver Unit Pharmacist, Dr Nick Foster and Dr Jonathan Sandoe, Microbiologists, Drs C Flynn and A Ford, Medical SpRs on Liver Unit and Mr A Shah, Surgical Transplant Fellow. Presentations were given on antibiotic prophylaxis in acute and sub-acute liver failure, antifungal prophylaxis in acute and sub-acute liver failure and in the post-transplant group and antibiotic prophylaxis in liver transplant surgery. A benchmarking exercise with other liver transplant units within the UK was also carried out.

The 2015 review was carried out by Dr Rebecca Jones (Hepatology), Dr Nicola Young (Microbiology) and Ms Rebecca Smith (Liver Unit Pharmacist) with input from Dr Tim Collyns (Microbiology) and Dr Phil Howard (Pharmacy). Since the original guideline was produced, the spectrum of resistant organism detection through CPE screening has increased in the liver transplant population, necessitating an individual approach for some patients which cannot be covered by a “cover-all” policy.

There is variation both within the UK and worldwide regarding approaches to prophylaxis, with evidence often being contradictory, hence the need for a consensus approach in the Leeds Liver Unit, being mindful of the published evidence and the experience of the unit.

Bacterial infection and surgical site infection remains a concern for post-liver transplant outcomes, and prophylaxis has to fit alongside an overall infection prevention approach throughout the unit, including scrupulous attention to hand hygiene and source isolation procedures.

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3. Special antimicrobial prophylaxis recommendations

1. MRSA prophylaxis in liver transplant surgery - as per LTHT guidelines, considering all such patients to be high risk as almost all will have spent some time hospitalised within 6 months of surgery. (C,D)

2. Antibiotic and antifungal prophylaxis in emergency transplantation for acute and sub-acute liver failure patients, where duration will depend somewhat on the presentation and recovery progress post-transplant, recognised to be highly heterogenous in this (rare) group. (C,D)

3. Antifungal prophylaxis post liver transplant and risk factors for invasive fungal infection (A)

4. Antibiotic prophylaxis post liver transplant surgery - as per LTHT guidelines for surgical prophylaxis taking into account whether patients are likely to be antibiotic naïve at point of surgery or not. (C,D)

Evidence level (A,B,C, D)

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. LTHT Consensus (no national guidelines exist, guidelines from different learned bodies contradict each other, or no evidence exists)

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Provenance

Record: 1824
Objective:
Clinical condition:

Liver transplant surgery in adults

Target patient group: Liver transplant patients
Target professional group(s): Pharmacists
Secondary Care Doctors
Adapted from:

Evidence base

  • Cheruvattath R and Balan V. Infections in patients with end-stage liver disease. J Clin Gastroenterol 2007;41:403-411
  • Rolando N et al. Bacterial and fungal infection in acute liver failure. Seminars in Liver Disease 1996;16:389-402
  • Snydman DR. Epidemiology of infections after solid-organ transplantation. Clinical Infectious Diseases 2001;33(suppl 1):S5-8
  • Kusne S and Blair JE. Viral and fungal infections after liver transplantation- Part II. Liver Transplantation 2006;12:2-11
  • Bratzler DW et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013;70:195-283
  • Garcia Prado ME et al. Surgical site infection in liver transplant recipients: impact of the type of perioperative prophylaxis. Transplantation 2008;85:1849-1854
  • Asensio A et al. Effect of antibiotic prophylaxis on the risk of surgical site infection in orthotopic liver transplant. Liver transplantation 2008;14:799-805
  • Singhal S et al. Targeted prophylaxis with amphotericin B lipid complex in liver transplantation. liver Transplantation 2000;6:588-595
  • Cruciani M et al. Antifungal prophylaxis in liver transplant patients: a systematic review and meta-analysis. Liver Transplantation 2006;12:850-858
  • Playford EG et al. Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients. Eur J Clin Microbiol Infect Dis 2006;25:549-561
  • Hellinger WC et al. Risk stratification and targeted antifungal prophylaxis for prevention of aspergillosis and other invasive mold infections after liver transplantation. Liver Transplantation 2005;11:656-662
  • Singh N et al. Antifungal management practices in liver transplant recipients. American Journal of Transplantation 2008;8:426-431
  • Eschenauer GA et al. Antifungal prophylaxis in liver transplant recipients. Liver Transplantation 2009;15:842-858
  • Evans JD et al. Antifungal prophylaxis in liver transplantation: a systematic review and network meta-analysis. Am J Transplant 2014;14:2765-76
  • Vandecasteele E et al. Antimicrobial prophylaxis in liver transplant patients - a multicentre survey endorsed by the European Liver and Intestine Transplant Association. Transplant Int. 2010;23:182-190.
  • Mumtaz K et al. Universal prophylaxis or preemptive strategy for cytomegalovirus disease after liver transplantation: a systematic review and meta-analysis. Am J Transplant 2015;15:472-481
  • Hodson EM et al. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev 2013;2:CD003774.doi:10.1002/14651858.CD003774.pub4
  • Rolando et al. Antibiotics in humans with acute liver failure: A randomised controlled trial. Hepatology 1993;17:196-201
  • Rolando et al. Antibiotics in humans with acute liver failure. J Antimicrob Chemother 1992;30:215-220
  • Salmeron et al. Antibiotics in humans with acute liver failure: an observational study. J Hepatol 1992;14:280-285
  • Adamu B et al. Antibiotic prophylaxis for preventing post solid organ transplant tuberculosis. Cochrane Database Syst Rev 2014 3:CD008597.doi:10.1002/14651858
  • Fabrega E et al. Chemoprophylaxis with isoniazid in liver transplant recipients. Liver transplantation 2012;18:1110-1117
  • Rajagopala S et al. Latent Mycobacterium tuberculosis infection in liver transplant recipients - controversies in current diagnosis and management. J Clin Exp Hepatol 2011;1:34-37
  • Holty JE et al. Tuberculosis in liver transplant recipients: a systematic review and meta-analysis of individual patient data. Liver Transplantation 2009;15:894-906
  • Sarwar S et al. Low incidence of Pneumocystis jirovecii pneumonia in an unprophylaxed liver transplant cohort. Transpl Infect Dis. 2013;15:510-515
  • Trotter JF et al. Absence of Pneumocystis jiroveci pneumonia in liver transplantation recipients receiving short-term (3-month) prophylaxis.Transpl Infect Dis. 2008 Oct;10(5):369-71.

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Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

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