Liver transplantation infection

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Liver trasnsplantation Microchapters

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Patient Information

Overview

Historical Perspective

Indications

Pre-surgical management

Choice of donor

Epidemiology and Demographics

Techniques

Complications

Acute rejection

Immune therapy

Post-surgical infection

Prognosis

Overview

Liver transplantation infection

Timing of infection

First month after transplantation

  • Endemic infections should be considered in the differential diagnosis of posttransplant infection.
Infectious complications related to surgery
  • Solid organ transplant recipients develop many of the common postoperative complications, such as aspiration pneumonia, surgical site infections, urinary tract infection, or pulmonary embolus.[4]
  • Transplant recipients are also at unique risk for superinfection of ischemic or injured graft tissues or of fluid collections.
  • These patients are at increased risk for infection associated with indwelling vascular access catheters, urinary catheters, and surgical drains.
  • The organisms responsible for such postoperative complications are often the bacteria and fungi of the local flora of the hospital.
  • Infections acquired before transplantation include relatively resistant nosocomial pathogens and pathogens such as aspergillus spp that are resistant to the usual prophylactic agents.
  • Patients receiving antimicrobial agents are at increased risk for C. difficile colitis.
  • Patients at particular risk of nosocomial infection are:
  • Patients with prolonged ventilation
  • Persistent ascites
  • Patients with intravascular clot or ischemic graft tissue[5]

1 to 6 months after transplantation

Major infections due to opportunistic pathogens include:

More than 6 to 12 months after transplantation

Prevention and treatment

  • Screening potential liver donors and recipients for infection.[10]
  • Appropriate vaccinations before transplantation since antirejection immunosuppressive medications may prevent optimal responses to vaccination post-transplantation.[11]
  • Certain vaccines such as pneumococcal and influenza vaccines should be repeated after transplantation in an attempt to lower the risk for these diseases. live vaccines should be avoided in transplant recipients due to the risk of disseminated disease.

Pneumocystis jirovecii

  • Antibiotics are administered at transplantation in an attempt to prevent SSIs, including wound and intraabdominal infection, although they do not provide complete protection.[12]
  • Skin and intestinal flora are common SSI pathogens, and it is important to recognize local epidemiologic patterns and recent colonizing or infecting organisms in the transplant recipient and donor when choosing antibiotics for prophylaxis. The use of antibacterial agents around the time of transplantation is discussed separately.[13]
  • In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation.
  • primarily to reduce the risk of Pneumocystis jirovecii (formerly P. carinii) pneumonia (PCP), but it also helps to prevent infections with Listeria monocytogenes, Nocardia asteroides, Toxoplasma gondii, and many common urinary, respiratory, and gastrointestinal bacterial pathogens.[14]
  • One single-strength tablet is taken daily or one double-strength tablet is taken three times weekly. Routine use of trimethoprim-sulfamethoxazole prophylaxis has virtually eliminated PCP infection in the posttransplant setting in comparison with a 10 to 12 percent incidence in earlier series.
  • The most common adverse effect of trimethoprim-sulfamethoxazole is allergy. Myelosuppression can also occur, Cytomegalovirus (CMV) the most important viral infection in liver transplant recipients. CMV infection, the presence of the virus in blood, tissue, or body fluids, should be distinguished from CMV disease, which is CMV infection accompanied by signs and symptoms of CMV.
  • Ganciclovir and valganciclovir have been incorporated into strategies designed to prevent CMV disease in patients at risk of CMV reactivation.[15]
  • As a result, the incidence of CMV disease in the posttransplant setting has declined.[16]

Cytomegalovirus

  • liver transplant recipients who are seronegative for CMV and receive an organ from a CMV-seropositive donor have the highest risk for developing CMV disease.
  • CMV-seropositive recipients have a modest risk.
  • CMV D-/R- recipients have the lowest risk.[17]
  • CMV infection has been associated with an accelerated course of hepatitis C virus recurrence.[18]
  • Prophylaxis: giving an anti-CMV drug to those at increased risk of CMV reactivation. Use antiviral CMV prophylaxis for three to six months after transplant and during intensification of immunosuppression for rejection.[19]
  • CMV prophylaxis reduced the risk of biopsy-proven rejection in liver transplant recipients.[20]
  • Treatment: giving an anti-CMV drug only when there is evidence of CMV replication. Valganciclovir, at doses of 900 mg daily is the main drug for treatment.[21]

Candida

  • Candida is the predominant fungal infection encountered after liver transplantation.
  • Candida prophylaxis for adult liver transplant recipients with ≥2 of the following risk factors:[22]
  • Prolonged or repeat operation
  • Retransplantation
  • Renal failure
  • High transfusion requirement
  • Choledochojejunostomy
  • Candida colonization during the perioperative period
  • Prophylaxis: Fluconazole 400 mg orally daily is the drug of choice.The duration of Candida prophylaxis should be one to four weeks or for as long as risk factors persist.

Aspergillus

  • Aspergillus infections occur in patients with certain risk factors.
  • Risk factors for Aspergillus infection after liver transplantation include fulminant hepatic failure, reoperation, retransplantation, posttransplant renal or hepatic failure, concurrent cytomegalovirus infection, hepatitis C infection, and high-dose glucocorticoids.
  • Prophylaxis: fluconazole prophylaxis decreased invasive fungal infections by 75 percent.[23]
  • The most common site of aspergillosis is the lung, although it may disseminate to other sites including the central nervous system (CNS).
  • It is the most common cause of CNS infection in liver transplant recipients, accounting for 55 percent of brain abscesses in one series.[24]
  • Mortality of aspergillosis in early series of liver transplant recipients approached 100 percent [100], but more recent data suggest the outcomes may be improving.[25]
    • Other types
  • Nosocomial pneumonias are particularly frequent in patients who require prolonged mechanical ventilation.
  • Pseudomonas aeruginosa and Enterobacter species may be recovered from bronchoalveolar lavage specimens. Other common bacterial pathogens associated with pneumonia include Staphylococcus aureus, Klebsiella pneumonia, Stenotrophomonas maltophilia, and Citrobacter freundii
  • Clostridium difficile colitis can also occur, particularly in the early period following transplantation and in patients requiring prolonged hospitalization. In fact, liver transplantation has been identified as a significant risk factor for C. difficile acquisition in the hospital.[26]
  • If a bacterial infection is suspected in a liver transplant recipient, empiric broad-spectrum antibiotics should be initiated until the specific bacterium and its sensitivities can be identified. Antibiotic regimens used for empiric therapy in the early posttransplantation period should include coverage for gram-positive cocci, gram-negative bacilli and anaerobes, with selection of agents that cover resistant organisms that have already been documented in the patient while awaiting microbiological test results. Candida is also an important pathogen during the first month after transplantation. The bloodstream, surgical wounds, and the urinary tract are common sites for primary infection, which may then disseminate.[27]
  • Candida infections may also manifest as esophagitis and superficial infections of the skin (folliculitis) or oral cavity.[28]

After six months

  • Opportunistic infections are uncommon beyond six months post-transplant in patients who have good graft function since immunosuppression usually get tapered.
  • These patients usually develop the same types of community-acquired infections seen in the general population, although at an increased rate.[29]
  • Transplant recipients may be more susceptible to some pathogens such as Legionella [103] and may experience more severe manifestations of certain infections such as West Nile virus infection.
  • Patients on chronic immunosuppression often initially have only subtle findings of infection due to attenuation of inflammatory responses by immunosuppressants, but this may be followed by a precipitous decline in status and severe manifestations of infection. Respiratory infections due to pathogens such as Streptococcus pneumoniae and Haemophilus influenzae can be life threatening if not promptly treated. Patients who have chronic rejection are also more susceptible to chronic viral infections, possibly from the increased immunosuppressive regimens. Chronic or recurrent viral infections including those due to EBV, CMV, hepatitis B (HBV), hepatitis C (HCV), and human herpesviruses 6 and 7 also can lead to complications in the late posttransplant period.[30]
  • Chronic viral infections such as HBV and HCV can also produce damage to the liver allograft.
  • Secondary tumors can occur also, especially posttransplant lymphoproliferative disease due to EBV and hepatocellular carcinoma due to HBV or HCV.
  • Hepatitis E virus can also cause chronic hepatitis in liver transplant recipients and should be considered in patients with unexplained liver enzyme elevations.[31]

References

  1. Hocevar SN, Paddock CD, Spak CW, Rosenblatt R, Diaz-Luna H, Castillo I; et al. (2014). "Microsporidiosis acquired through solid organ transplantation: a public health investigation". Ann Intern Med. 160 (4): 213–20. doi:10.7326/M13-2226. PMC 4627638. PMID 24727839.
  2. Chong PP, Razonable RR (2013). "Diagnostic and management strategies for donor-derived infections". Infect Dis Clin North Am. 27 (2): 253–70. doi:10.1016/j.idc.2013.02.001. PMID 23714339.
  3. Gupte AA, Hocevar SN, Lea AS, Kulkarni RD, Schain DC, Casey MJ; et al. (2014). "Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management". Am J Transplant. 14 (6): 1417–24. doi:10.1111/ajt.12726. PMC 4642815. PMID 24840013.
  4. Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S (2002). "Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient". Transplantation. 74 (11): 1645–7. doi:10.1097/01.TP.0000038746.35254.A4. PMID 12490804.
  5. Fishman JA (2003). "Vancomycin-resistant Enterococcus in liver transplantation: what have we left behind?". Transpl Infect Dis. 5 (3): 109–11. PMID 14617297.
  6. Fishman JA (1998). "Treatment of infection due to Pneumocystis carinii". Antimicrob Agents Chemother. 42 (6): 1309–14. PMC 105593. PMID 9624465.
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  9. Russell DL, Flood A, Zaroda TE, Acosta C, Riley MM, Busuttil RW; et al. (2008). "Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients". Am J Transplant. 8 (8): 1737–43. doi:10.1111/j.1600-6143.2008.02304.x. PMID 18557723.
  10. Fishman JA (2014). "From the classic concepts to modern practice". Clin Microbiol Infect. 20 Suppl 7: 4–9. doi:10.1111/1469-0691.12593. PMID 24528498.
  11. Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S (2002). "Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient". Transplantation. 74 (11): 1645–7. doi:10.1097/01.TP.0000038746.35254.A4. PMID 12490804.
  12. Martin SI, Fishman JA, AST Infectious Diseases Community of Practice (2013). "Pneumocystis pneumonia in solid organ transplantation". Am J Transplant. 13 Suppl 4: 272–9. doi:10.1111/ajt.12119. PMID 23465020.
  13. Fishman JA, Rubin RH (1998). "Infection in organ-transplant recipients". N Engl J Med. 338 (24): 1741–51. doi:10.1056/NEJM199806113382407. PMID 9624195.
  14. Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G; et al. (2017). "Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials". Clin Infect Dis. 64 (1): 87–91. doi:10.1093/cid/ciw668. PMID 27682069.
  15. Park JM, Lake KD, Arenas JD, Fontana RJ (2006). "Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients". Liver Transpl. 12 (1): 112–6. doi:10.1002/lt.20562. PMID 16382458.
  16. Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B; et al. (2004). "Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients". Am J Transplant. 4 (4): 611–20. doi:10.1111/j.1600-6143.2004.00382.x. PMID 15023154.
  17. Marcelin JR, Beam E, Razonable RR (2014). "Cytomegalovirus infection in liver transplant recipients: updates on clinical management". World J Gastroenterol. 20 (31): 10658–67. doi:10.3748/wjg.v20.i31.10658. PMC 4138447. PMID 25152570.
  18. Razonable RR, Burak KW, van Cruijsen H, Brown RA, Charlton MR, Smith TF; et al. (2002). "The pathogenesis of hepatitis C virus is influenced by cytomegalovirus". Clin Infect Dis. 35 (8): 974–81. doi:10.1086/342911. PMID 12355385.
  19. Fishman JA (2007). "Infection in solid-organ transplant recipients". N Engl J Med. 357 (25): 2601–14. doi:10.1056/NEJMra064928. PMID 18094380.
  20. Slifkin M, Ruthazer R, Freeman R, Bloom J, Fitzmaurice S, Fairchild R; et al. (2005). "Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation". Liver Transpl. 11 (12): 1597–602. doi:10.1002/lt.20523. PMID 16315314.
  21. Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L; et al. (2013). "Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation". Transplantation. 96 (4): 333–60. doi:10.1097/TP.0b013e31829df29d. PMID 23896556.
  22. Husain S, Tollemar J, Dominguez EA, Baumgarten K, Humar A, Paterson DL; et al. (2003). "Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study". Transplantation. 75 (12): 2023–9. doi:10.1097/01.TP.0000065178.93741.72. PMID 12829905.
  23. Playford EG, Webster AC, Sorrell TC, Craig JC (2006). "Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients". Eur J Clin Microbiol Infect Dis. 25 (9): 549–61. doi:10.1007/s10096-006-0182-3. PMID 16912905.
  24. Bonham CA, Dominguez EA, Fukui MB, Paterson DL, Pankey GA, Wagener MM; et al. (1998). "Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management". Transplantation. 66 (12): 1596–604. PMID 9884245.
  25. Barchiesi F, Mazzocato S, Mazzanti S, Gesuita R, Skrami E, Fiorentini A; et al. (2015). "Invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases". Liver Transpl. 21 (2): 204–12. doi:10.1002/lt.24032. PMID 25348192.
  26. Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW (1994). "Clostridium difficile colonization and diarrhea at a tertiary care hospital". Clin Infect Dis. 18 (2): 181–7. PMID 8161624.
  27. Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R; et al. (2016). "Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America". Clin Infect Dis. 63 (4): e1–e60. doi:10.1093/cid/ciw326. PMC 4967602. PMID 27365388.
  28. Colonna JO, Winston DJ, Brill JE, Goldstein LI, Hoff MP, Hiatt JR; et al. (1988). "Infectious complications in liver transplantation". Arch Surg. 123 (3): 360–4. PMID 2829792.
  29. Fishman JA (2007). "Infection in solid-organ transplant recipients". N Engl J Med. 357 (25): 2601–14. doi:10.1056/NEJMra064928. PMID 18094380.
  30. Galante A, Pischke S, Polywka S, Luetgehethmann M, Suneetha PV, Gisa A; et al. (2015). "Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting". Transpl Infect Dis. 17 (4): 617–22. doi:10.1111/tid.12411. PMID 26094550.
  31. Kumar D, Prasad GV, Zaltzman J, Levy GA, Humar A (2004). "Community-acquired West Nile virus infection in solid-organ transplant recipients". Transplantation. 77 (3): 399–402. doi:10.1097/01.TP.0000101435.91619.31. PMID 14966414.