Liver disease or transplant - prevention and management of infection
Management of complications from liver disease or transplant
Antibiotic choice in liver disease and transplant
Transplant prophylaxis
Elective patients | |
Standard patients | Cefazolin 30 mg/kg (maximum 2 g) IV, q8h for 24 hours from the time of induction (three doses): First dose given at induction, repeat dose if surgery >4 hours or if excessive blood loss |
Penicillin anaphylaxis (not "rash") or MRSA colonisation | Vancomycin 15mg/kg (max 2g)IV q6h for 24 hours from the time of induction (four doses) and Gentamicin single dose IV; 5mg/kg (max 360mg) administered as a 30 minute infusion. |
ESBL+ve MRO colonisation | Cefazolin IV and Amikacin single dose IV; 15mg/kg (max 1500mg) administered as a 30 minute infusion. MRO status and any special requirements are to be documented on the transplant waiting list |
Sclerosing cholangitis/recurrent bacterial cholangitis | Standard regimens as above, making certain that the regimen is effective in vitro against the last isolated infecting organism. If not, discuss alternative or additional antibiotic with the Infectious Disease service. |
Transplant for acute liver failure (ALF), re-transplant for primary non-function | |
Standard patients | Cefazolin 30 mg/kg (maximum 2 g) IV q8h for 48 hours from the time of induction (six doses) |
Penicillin anaphylaxis (not "rash") or MRSA colonisation | Vancomycin 15 mg/kg IV q6h for 48 hours from the time of induction (8 doses) and Gentamicin 5mg/kg (max 360mg) IV q24h for 48 hours (2 doses) |
ESBL+ve MRO colonisation | Cefazolin 30 mg/kg (maximum 2 g) IV q8h for 48 hours from the time of induction (6 doses) AND Amikacin IV 15 mg/kg (max 1500 mg) q24 hr for 48 hours (2 doses) |
Antifungal prophylaxis: (ALF, retransplant and second laparotomy) | Liposomal amphotericin 1mg/kg IV daily for 5 days |
Percutaneous transhepatic cholangiography (PTC) ± ERCP ± cholangiography
For procedure | Amoxicillin 50mg/kg (max 2g) IV q8h at induction (single dose or continue for 24 hours (total three doses) if complicated) and Gentamicin single dose IV; 5mg/kg (max 360mg) administered as a 30 minute infusion |
Oral prophylaxis for children with PTC tube or biliary stent | Co-trimoxazole 12mg/kg combined (max 480mg) oral once daily |
Liver biopsy
Immunosuppressed patients but otherwise at low risk for biliary complications | Cefazolin 30mg/kg (max 2g) IV given at induction as a single dose |
High risk patients (unwell or biliary complications) | Amoxicillin 50mg/kg (max 2g) IV q8h for 24 hours and Gentamicin 5mg/kg (max 360mg) IV; single dose. If there is renal impairment replace gentamicin with ceftriaxone 50mg/kg (max 1g) IV single dose. |
Cholangitis
First Line therapy | Amoxicillin 50mg/kg (max 2g) IV q8h and Gentamicin 7mg/kg (max 360mg) IV q24h. If there is renal impairment replace gentamicin with ceftriaxone 50mg/kg 24 hourly IV (max 1g per dose) Treat for 7 days |
Second line therapy | Piperacillin-tazobactam 90mg/kg (max 4.5g) IV q8h |
Suspected respiratory infection Cefuroxime 30mg/kg (max 1.5g) IV q8h | |
Abdominal sepsis Amoxicillin 50mg/kg (max 2g) IV q8h and Metronidazole 7.5mg/kg (max 500mg) IV q8h and Gentamicin 7mg/kg (max 360mg) IV q24h or if there is renal impairment replace gentamicin with ceftriaxone 50mg/kg 24 hourly IV (max 1g per dose) NB: If there is evidence of wound infection then consider rationalising to amoxicillin clavulanate ( to provide staphylococcal cover) plus gentamicin |
Spontaneous Bacterial Peritonitis
Initial therapy | Amoxicillin 50mg/kg (max 2g) IV q8h and Gentamicin 7mg/kg (max 360mg) IV q24h. If there is renal impairment replace gentamicin with ceftriaxone 50mg/kg 24 hourly IV (max 1g per dose) Antibiotic choice to be altered according to results of ascitic tap |
Prophylaxis | Co-trimoxazole 12mg/kg (max 480mg) oral once daily |
Recurrent cholangitis | Co-trimoxazole 12mg/kg combined (max 480mg) oral once daily 2 weeks alternating with Ciprofloxacin 10mg/kg (max 500mg) oral bd 2 weeks This requires ID approval, and NPPA funding for community use. |
Antifungal prophylaxis after transplant
All patients | Nystatin 1mL (100,000 units/mL) orally q6h for four weeks post-transplant "Swish and swallow" if able, give via NG tube if unable to swallow and if NG tube is present. |
Transplant for acute liver failure or re-transplant or "return to theatre" | Liposomal amphotericin B 1mg/kg IV daily for 5 days Begin when listed for transplantation for transplant for acute liver failure and re-transplant. Give at time of return to theatre for "return to theatre" |
Suspected invasive fungal infection | Discuss with Infectious Diseases Service |
PJP prophylaxis after transplant
Begin one week after transplant and continue until 12 months post-transplantation, re-transplantation or treatment for acute rejection
Co-trimoxazole 15mg/kg combined orally bd for three days per week (e.g. MWF or FSS)
For patients with allergy to co-trimoxazole and are unable to be de-sensitised | |
High risk patients (CMV mismatch, previous PJP infection, thymoglobulin therapy) | Discuss alternatives such as pentamidine or dapsone with Infectious Diseases Service. |
Low risk patients | Consider close monitoring without PJP prophylaxis |
Antiviral CMV prophylaxis after transplant
All patients receive prophylaxis post OLT; Start prophylaxis before day 10 provided
Platelet count >50 x 10⁹/L
Neutrophil count >1.0 x 10⁹/L
CMV and EBV status of donor and recipient to be formally documented in the clinical record.
Donor CMV Status | Confirm status with transplant co-ordinators. |
Recipient CMV/EBV Status | Assessed at listing and at time of transplant |
Monitoring: All patients | Monitor CMV/EBV viral load (2mL EDTA tube) 4 weekly post liver transplant for 12 months Lab requirements: Individualised Lab request form and samples otherwise not processed |
Prophylaxis
Valganciclovir 520mg/m2 (max 900mg) orally once daily
When patients are unable tolerate enteral administration by Day 10, IV ganciclovir prophylaxis can be used until enteral administration is possible.
Ganciclovir 5mg/kg IV q24h
Total duration of prophylaxis (valganciclovir and ganciclovir) is 12 weeks
Valganciclovir is a prodrug that is converted to ganciclovir which is teratogenic. Tablets should not be crushed unless required to give a part dose to smaller children. Doses should always be rounded to the nearest quarter of a tablet (i.e. 1 tablet = 450mg, ¾ tablet = 337.5mg, ½ tablet = 225mg, ¼ tablet = 112.5mg). Caregivers must be educated how to crush and administer this medicine with necessary precautions to reduce unnecessary exposure. Valganciclovir requires special authority approval prior to discharge.
A liquid formulation can be compounded by pharmacies that have the appropriate safety equipment (still air box).
The dose of valganciclovir and ganciclovir should be reduced in renal impairment according to the following algorithms (Amended from UCSF Children's Hospital)
Patients receiving thymoglobulin therapy
Start prophylaxis on day 1 of thymoglobulin therapy if:
Platelet count >50 x 10⁹/L
Neutrophil count >1.0 x 10⁹/L
Ganciclovir 5 mg/kg IV q24h until the patient is able to swallow tablets and then switch to oral valganciclovir 520mg/m2 daily for total treatment duration of six weeks. NB: Valganciclovir will require NPPA approval for this indication. Reduce doses in patients with renal impairment according to the above algorithms.
CMV treatment
Asymptomatic
Viral load < 2.5 logs - repeat in 3-7 days
Viral load ≥ 2.5 logs - treat for 14 days (treatment dose ganciclovir or valganciclovir) -repeat PCR and if negative complete 21 days and stop. Resume monthly surveillance.
Symptomatic/ tissue invasive disease irrespective of initial CMV viral load
Treatment dose valganciclovir
CNS/severe/significant GI disease: IV ganciclovir until stable and then switch to valganciclovir
PCR (viral load) monitoring weekly. Continue treatment for two weeks after viral load negative
Tissue positive PCR with negative serum PCR
Valganciclovir treatment dose 2-3 weeks - using precipitating symptom as treatment guide
Failure to respond to treatment
In the absence of an alternative diagnosis:
Ongoing symptomatology with positive serum PCR or
Ongoing symptomatology in patient with initial serum PCR negative
Consider change to alternative agent (especially in previous CMV disease or previous valganciclovir treatment):
Discuss with Infectious Diseases Service
Consider further tissue specimen
If no previous CMV and no previous valganciclovir treatment then consider stopping
GFR (ml/min/1.73m2) | Dose recommendation |
Valganciclovir | Standard dose = 520 mg/m2 (max 900 mg twice daily) |
> 60 | No dose reduction |
40-59 | 260mg/m2 (max 450mg) once daily |
25-39 | 260mg/m2 (max 450mg) alternate days |
10-24 | 260mg/m2 (max 450mg) twice a week |
<10 | Avoid; use ganciclovir as below |
Ganciclovir | |
>70 | No dose reduction |
50-70 | 5mg/kg q24h |
25-50 | 2.5mg/kg q24h |
10-25 | 1.25mg/kg q24h |
<10 (or on HD) | 1.25mg/kg q48h |
EBV Treatment
Monitor CMV/EBV viral load (2mL EDTA tube) 4 weekly post liver transplant for 12 months. Monitoring continues if the patient has demonstrated persistent carriage. Discontinue at 12 months if negative; for testing as clinically indicated.
If there is a rising viral load
Reduction of immunosuppression as clinically appropriate
Discuss with Infectious Diseases Service - antivirals will need NPPA approval
Review for evidence of PTLD/ EBV infection
Repeat viral load in 2 weeks
Liver transplant immunisation
For further information on immunisations please refer to the current Immunisation Schedule in the Immunisation Handbook or www.immune.org.nz
Post-transplant | |
6 months post-transplant | Hep A and B revaccination for non-immune patients Pneumococcal vaccine (23PPV) |
12 months post-transplant | Resume schedule immunisations -not live vaccines unless in discussion, benefit deemed to exceed risks |
Annual check | Measles/ varicella immune status. Discuss with infectious diseases team if non-immune Hepatitis A/B immune status. Revaccinate if non-immune Annual influenza immunization for patient. Recommend vaccination for siblings and parents |
Ensure routine immunisation of siblings is up-to-date and recommend varicella vaccine for all non-immune household members. Varicella vaccine is funded for susceptible household contacts of transplant patients. |
The Starship liver team will advise when it is safe to recommence vaccination after transplant. These patients will be on the accelerated immunisation schedule as per the national immunisation handbook - vaccines for special groups.
COVID-19 vaccine
It is recommended that all eligible post-transplant patients receive the 3 primary vaccines as per the Ministry of Health guidelines, and any boosters required (if not given prior to transplant).
Live vaccines post liver transplant
Live vaccines are not generally indicated post liver transplant due to the risk of immunosuppression.
However Varicella and MMR vaccination can be considered if the recipient is greater than 1 year post liver transplant and maintained on low level single agent immunosuppression. The decision needs to be discussed with the Starship liver team prior to administration.
Accelerated immunisation schedule (funded) for infants in whom liver or kidney transplant is likely
Refer to the Pharmaceutical Schedule (www.pharmac.govt.nz) for any changes to funding decisions. See Ministry of Health funded vaccines for special groups for accelerated immunisation schedule.
Post-transplant patients should receive immunoglobulin (IG) prophylaxis* if Varicella or Measles exposed AND:
known seronegative
OR if status is unknown and urgent result cannot be obtained
OR if patient has recently had increased immunosuppression (pulse steroids/ ATG/ increased baseline IS) without subsequent VZV/measles IgG result.
*For varicella exposure IG prophylaxis is given as VZIG (i.m.) or IVIG as soon as possible, but up to 10 days following exposure may be beneficial. If IG given greater than 96hours post exposure Acyclovir can also be offered for post exposure prophylaxis: oral acyclovir 20mg/ kg four times daily for 7 days from day 7 post exposure, plus strict instruction to present to medical care if lesions develop. In severely immune suppressed patients both modalities may be offered.
For measles exposure IG prophylaxis is given as normal IG (i.m.) or IVIG, as soon as possible within 6 days of exposure.
Additionally, ensure household contacts are immunised/ have immunity:
Varicella vaccine is now funded for all household contacts of immunosuppressed patients and should be given to household contacts with no prior history of chicken pox or vaccination
MMR vaccine is on the National Immunisation schedule and is free for any susceptible individual: all household contacts should have received 2 doses of measles containing vaccine (unless born prior to 1969).
Note: There is no prophylaxis available for mumps