Liver transplantation infection
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
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Liver trasnsplantation Microchapters |
Overview
Liver transplantation infection
- Infection is the most frequent cause of death following liver transplantation.
- The most common types of infection were bacterial, fungal, and viral.
- Infections that are derived from donor organ tissues and activated in the recipient are among the most important exposures in transplantation [18-22].
- Clusters of infection associated with organ transplantation include Mycobacterium tuberculosis, Candida and Aspergillus, herpes simplex virus, human herpes virus 8, lymphocytic choriomeningitis virus (LCMV) [24-27], rabies virus [28-30], Trypanosoma cruzi, Balamuthia mandrillaris [31-34], Encephalitozoon cuniculi [35], HIV, and hepatitis C virus.
Timing of infection
First month after transplantation
- Infection derived from either the donor or recipient and infectious complications of the transplant surgery and hospitalization.
- Endemic infections should be considered in the differential diagnosis of posttransplant infection.
- Solid organ transplant recipients develop many of the common postoperative complications, such as aspiration pneumonitis, surgical site infections, urinary tract infection, or pulmonary embolus. [57]
- Transplant recipients are also at unique risk for superinfection of ischemic or injured graft tissues (eg, anastomotic suture lines) or of fluid collections (eg, hematomas, lymphoceles, pleural effusions, urinomas). 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 that have colonized the recipient or donor (eg, the lungs and/or sinuses in cystic fibrosis) prior to transplantation or the local flora of the hospital. Infections acquired prior to transplantation may include relatively resistant nosocomial pathogens (eg, vancomycin-resistant enterococcus) 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 those requiring prolonged ventilatory support or those with diminished lung function, persistent ascites, stents of the urinary tract or biliary ducts, with intravascular clot or ischemic graft tissue [49,58].
1 to 6 months after transplantation
Major infections due to opportunistic pathogens include:
- Pneumocystis jirovecii and protozoal diseases including toxoplasmosis, leishmaniasis, and Chagas disease [8,47,48,59-61]
- The geographic or endemic fungal infections caused by Histoplasma capsulatum, Coccidioides spp, and Cryptococcus
- Viral pathogens, particularly the herpes group viruses but also hepatitis B and hepatitis C
- Respiratory viruses are influenza, parainfluenza, respiratory syncytial virus, adenovirus, metapneumovirus.
- Tuberculosis and nontuberculous mycobacteria [62]
More than 6 to 12 months after transplantation
- Community-acquired pneumonias due to respiratory viruses, the pneumococcus, Legionella, or other common pathogens. community-acquired infections due to influenza or Listeria monocytogenes.
- Pretransplant colonization of liver transplant recipients with organisms such as methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) can lead to posttransplant infection with these organisms [11-13].
Prevention and treatment
screening potential liver donors and recipients for infection as noted above [8] [9]
Vaccination appropriate vaccinations before transplantation since antirejection immunosuppressive medications may prevent optimal responses to vaccination post-transplantation [21].
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 [24]. 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.
In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation [25], 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 [8,25-27]. 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 [26].
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 [29].
Ganciclovir and valganciclovir have been incorporated into strategies designed to prevent CMV disease in patients at risk of CMV reactivation [30-32]. As a result, the incidence of CMV disease in the posttransplant setting has declined [33,34]
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. [36]
- CMV infection has been associated with an accelerated course of hepatitis C virus recurrence. [41,42].
- 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. CMV prophylaxis reduced the risk of biopsy-proven rejection in liver transplant recipients [50]. [8]
- 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. 52,53
Candida
- Candida is the predominant fungal infection encountered after liver transplantation [56].
- Candida prophylaxis for adult liver transplant recipients with ≥2 of the following risk factors [57]:
- 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 [58].
- Prophylaxis: fluconazole prophylaxis decreased invasive fungal infections by 75 percent. [66].
- 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 [99].
- Mortality of aspergillosis in early series of liver transplant recipients approached 100 percent [100], but more recent data suggest the outcomes may be improving. [97,101].
- 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 [4].
- 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 [78].
- 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 [56].
- Candida infections may also manifest as esophagitis and superficial infections of the skin (folliculitis) or oral cavity [4].
After six months
- Opportunistic infections are uncommon beyond six months post-transplant in patients who have good graft function since immunosuppression has generally been tapered to a maintenance regimen.
- These patients usually develop the same types of community-acquired infections seen in the general population, although at an increased rate [8].
- 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 [104]
- 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.
- Chronic viral infections can also produce damage to the liver allograft (HBV and HCV) or cause secondary tumors during this period, including posttransplant lymphoproliferative disease due to EBV and hepatocellular carcinoma due to HBV or HCV [35]. Hepatitis E virus (HEV) can also cause chronic hepatitis in liver transplant recipients and should be considered in patients with unexplained liver enzyme elevations [105].