Liver transplantation infection: Difference between revisions

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==Overview==
==Overview==
[[Infection]] is the most frequent cause of death following liver transplantation. According to the timing, infection can be divided into three sections; First month after transplantation, 1 to 6 months after transplantation, and more than 6 to 12 months after transplantation. Prevention of infection includes [[Screening (medicine)|Screening]] potential liver donors and recipients for infection, certain [[vaccines]] such as [[pneumococcal]] and [[Influenza vaccine|influenza vaccines]] should be repeated after transplantation in an attempt to lower the risk for these diseases. Empiric [[broad-spectrum antibiotics]] should be initiated if a bacterial infection is suspected in a liver transplant recipient until the specific bacterium and its sensitivities can be identified. Antibiotic regimens should include coverage for [[gram-positive cocci]], [[gram-negative bacilli]] and [[anaerobes]]. In patients without [[sulfonamide]] [[allergy]], [[Sulfamethoxazole-Trimethoprim|trimethoprim-sulfamethoxazole]] is generally administered for 6 to 12 months after liver transplantation to reduce the risk of [[pneumocystis jirovecii]] [[pneumonia]], [[listeria monocytogenes]], [[nocardia]], and [[toxoplasma gondii]]. Prophylaxis of [[Cytomegalovirus infection|CMV]] includes [[Ganciclovir]] and [[valganciclovir]] are used to prevent [[Cytomegalovirus infection|CMV]] infection in patients at risk of CMV reactivation for three to six months. Prophylaxis of [[candida]] includes [[Fluconazole]] 400 mg orally daily is the drug of choice for one to four weeks or for as long as risk factors persist. Prophylaxis of [[aspergillosis]] includes [[Fluconazole]] prophylaxis decreased invasive fungal infections by 75 percent.
==Liver transplantation infection==
==Liver transplantation infection==
* Infection is the most frequent cause of death following liver transplantation.<ref name="pmid24727839">{{cite journal| author=Hocevar SN, Paddock CD, Spak CW, Rosenblatt R, Diaz-Luna H, Castillo I et al.| title=Microsporidiosis acquired through solid organ transplantation: a public health investigation. | journal=Ann Intern Med | year= 2014 | volume= 160 | issue= 4 | pages= 213-20 | pmid=24727839 | doi=10.7326/M13-2226 | pmc=4627638 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24727839  }}</ref>
* [[Infection]] is the most frequent cause of death following liver transplantation.<ref name="pmid24727839">{{cite journal| author=Hocevar SN, Paddock CD, Spak CW, Rosenblatt R, Diaz-Luna H, Castillo I et al.| title=Microsporidiosis acquired through solid organ transplantation: a public health investigation. | journal=Ann Intern Med | year= 2014 | volume= 160 | issue= 4 | pages= 213-20 | pmid=24727839 | doi=10.7326/M13-2226 | pmc=4627638 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24727839  }}</ref>
* The most common types of infection were bacterial, fungal, and viral.
* The most common types of infection were [[Bacteria|bacterial]], [[Fungus|fungal]], and [[Virus|viral]].
* Infections that are derived from donor organ tissues and activated in the recipient are among the most important exposures in transplantation.<ref name="pmid23714339">{{cite journal| author=Chong PP, Razonable RR| title=Diagnostic and management strategies for donor-derived infections. | journal=Infect Dis Clin North Am | year= 2013 | volume= 27 | issue= 2 | pages= 253-70 | pmid=23714339 | doi=10.1016/j.idc.2013.02.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23714339  }}</ref>
* Infections that are derived from donor organ tissues and activated in the recipient are among the most important exposures in transplantation.<ref name="pmid23714339">{{cite journal| author=Chong PP, Razonable RR| title=Diagnostic and management strategies for donor-derived infections. | journal=Infect Dis Clin North Am | year= 2013 | volume= 27 | issue= 2 | pages= 253-70 | pmid=23714339 | doi=10.1016/j.idc.2013.02.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23714339  }}</ref>
* Clusters of infection associated with organ transplantation include Mycobacterium tuberculosis, Candida and Aspergillus, herpes simplex virus, human herpes virus 8, lymphocytic choriomeningitis virus, rabies virus, Trypanosoma cruzi, Balamuthia mandrillaris, Encephalitozoon cuniculi, HIV, and hepatitis C virus.<ref name="pmid24840013">{{cite journal| author=Gupte AA, Hocevar SN, Lea AS, Kulkarni RD, Schain DC, Casey MJ et al.| title=Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management. | journal=Am J Transplant | year= 2014 | volume= 14 | issue= 6 | pages= 1417-24 | pmid=24840013 | doi=10.1111/ajt.12726 | pmc=4642815 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24840013  }}</ref>
* Infection associated with organ transplantation include [[mycobacterium tuberculosis]], [[candida]], [[aspergillus]], [[herpes simplex virus]], human herpes virus 8, [[lymphocytic choriomeningitis]] virus, [[rabies]] virus, [[trypanosoma cruzi]], [[balamuthia mandrillaris]], encephalitozoon cuniculi, [[Human Immunodeficiency Virus (HIV)|HIV,]] and [[hepatitis C virus]].<ref name="pmid24840013">{{cite journal| author=Gupte AA, Hocevar SN, Lea AS, Kulkarni RD, Schain DC, Casey MJ et al.| title=Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management. | journal=Am J Transplant | year= 2014 | volume= 14 | issue= 6 | pages= 1417-24 | pmid=24840013 | doi=10.1111/ajt.12726 | pmc=4642815 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24840013  }}</ref>


== Timing of infection ==
== Timing of infection ==


=== First month after transplantation ===
=== First month after transplantation ===
* Infection derived from either the donor or recipient and infectious complications of the transplant surgery and hospitalization.
* [[Endemic (epidemiology)|Endemic]] infections should be considered in the differential diagnosis of post-transplant infection.
* Endemic infections should be considered in the differential diagnosis of posttransplant infection.


====== Infectious complications related to surgery ======
* Liver transplant recipients develop many of the common postoperative infections such as [[aspiration pneumonia]], [[Surgical site infection|surgical site infections]], or [[urinary tract infection]].<ref name="pmid12490804">{{cite journal| author=Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S| title=Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient. | journal=Transplantation | year= 2002 | volume= 74 | issue= 11 | pages= 1645-7 | pmid=12490804 | doi=10.1097/01.TP.0000038746.35254.A4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12490804  }}</ref>  
* Solid organ transplant recipients develop many of the common postoperative complications, such as aspiration pneumonitis, surgical site infections, urinary tract infection, or pulmonary embolus.<ref name="pmid12490804">{{cite journal| author=Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S| title=Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient. | journal=Transplantation | year= 2002 | volume= 74 | issue= 11 | pages= 1645-7 | pmid=12490804 | doi=10.1097/01.TP.0000038746.35254.A4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12490804  }}</ref>  
* These patients are at increased risk for infection associated with indwelling [[Catheter-Based Interventions|vascular access catheters]], [[Urinary catheter|urinary catheters]], and surgical drains.  
* 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). 
* The organisms responsible for such postoperative complications are often the [[bacteria]] and [[Fungus|fungi]] of the local [[flora]] of the hospital.   
* 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 prior to transplantation or the local flora of the hospital.   
* Infections acquired before transplantation include relatively resistant [[Nosocomial infection|nosocomial]] pathogens and pathogens such as [[aspergillus|aspergillus spp]] that are resistant to the usual prophylactic agents.  
* 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:
* 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.<ref name="pmid14617297">{{cite journal| author=Fishman JA| title=Vancomycin-resistant Enterococcus in liver transplantation: what have we left behind? | journal=Transpl Infect Dis | year= 2003 | volume= 5 | issue= 3 | pages= 109-11 | pmid=14617297 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14617297  }}</ref>  
* Patients with prolonged [[Ventilation (physiology)|ventilation]]
* Persistent [[ascites]] 
* Patients with ischemic graft tissue<ref name="pmid14617297">{{cite journal| author=Fishman JA| title=Vancomycin-resistant Enterococcus in liver transplantation: what have we left behind? | journal=Transpl Infect Dis | year= 2003 | volume= 5 | issue= 3 | pages= 109-11 | pmid=14617297 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14617297  }}</ref>  
* Patients receiving [[Antimicrobial agent|antimicrobial agents]] are at increased risk for [[Clostridium difficile infection|C. difficile colitis]]


==== 1 to 6 months after transplantation ====
=== 1 to 6 months after transplantation ===
Major infections due to opportunistic pathogens include:
Major infections due to opportunistic pathogens include:
* Pneumocystis jirovecii and protozoal diseases including toxoplasmosis, leishmaniasis, and Chagas disease.<ref name="pmid9624465">{{cite journal| author=Fishman JA| title=Treatment of infection due to Pneumocystis carinii. | journal=Antimicrob Agents Chemother | year= 1998 | volume= 42 | issue= 6 | pages= 1309-14 | pmid=9624465 | doi= | pmc=105593 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9624465  }}</ref>
* Bacterial: [[tuberculosis]] and [[nontuberculous mycobacteria]]
* The geographic or endemic fungal infections caused by Histoplasma capsulatum, Coccidioides spp, and Cryptococcus.<ref name="pmid8651775">{{cite journal| author=Bocchi EA, Bellotti G, Mocelin AO, Uip D, Bacal F, Higuchi ML et al.| title=Heart transplantation for chronic Chagas' heart disease. | journal=Ann Thorac Surg | year= 1996 | volume= 61 | issue= 6 | pages= 1727-33 | pmid=8651775 | doi=10.1016/0003-4975(96)00141-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8651775  }}</ref>
* Viral pathogens, particularly the herpes group viruses but also hepatitis B and hepatitis C.
* Respiratory viruses are influenza, parainfluenza, respiratory syncytial virus, adenovirus, metapneumovirus.<ref name="pmid22075795">{{cite journal| author=Fernàndez-Sabé N, Cervera C, Fariñas MC, Bodro M, Muñoz P, Gurguí M et al.| title=Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: a matched case-control study. | journal=Clin Infect Dis | year= 2012 | volume= 54 | issue= 3 | pages= 355-61 | pmid=22075795 | doi=10.1093/cid/cir806 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22075795  }}</ref>
* Tuberculosis and nontuberculous mycobacteria


==== More than 6 to 12 months after transplantation ====
* Protozoal disease: [[toxoplasmosis]], [[leishmaniasis]], and [[Chagas disease]]<ref name="pmid9624465">{{cite journal| author=Fishman JA| title=Treatment of infection due to Pneumocystis carinii. | journal=Antimicrob Agents Chemother | year= 1998 | volume= 42 | issue= 6 | pages= 1309-14 | pmid=9624465 | doi= | pmc=105593 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9624465  }}</ref>
* Community-acquired pneumonias due to respiratory viruses, the pneumococcus, Legionella, or other common pathogens. community-acquired infections due to influenza or Listeria monocytogenes.
* Fungal infections: [[histoplasma capsulatum]], [[Coccidioides spp|coccidioides]] and [[Cryptococcosis|cryptococcus]]<ref name="pmid8651775">{{cite journal| author=Bocchi EA, Bellotti G, Mocelin AO, Uip D, Bacal F, Higuchi ML et al.| title=Heart transplantation for chronic Chagas' heart disease. | journal=Ann Thorac Surg | year= 1996 | volume= 61 | issue= 6 | pages= 1727-33 | pmid=8651775 | doi=10.1016/0003-4975(96)00141-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8651775  }}</ref>
* 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.<ref name="pmid18557723">{{cite journal| author=Russell DL, Flood A, Zaroda TE, Acosta C, Riley MM, Busuttil RW et al.| title=Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients. | journal=Am J Transplant | year= 2008 | volume= 8 | issue= 8 | pages= 1737-43 | pmid=18557723 | doi=10.1111/j.1600-6143.2008.02304.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18557723  }}</ref>
* Viral infection: [[Herpes simplex virus|herpes virus]], [[hepatitis B]] and [[hepatitis C]]
* Respiratory viruses: [[influenza]], [[Parainfluenza virus|parainfluenza]], [[respiratory syncytial virus]], [[adenovirus]], and [[metapneumovirus]].<ref name="pmid22075795">{{cite journal| author=Fernàndez-Sabé N, Cervera C, Fariñas MC, Bodro M, Muñoz P, Gurguí M et al.| title=Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: a matched case-control study. | journal=Clin Infect Dis | year= 2012 | volume= 54 | issue= 3 | pages= 355-61 | pmid=22075795 | doi=10.1093/cid/cir806 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22075795  }}</ref>
 
=== More than 6 to 12 months after transplantation ===
* LT patients are susceptible for [[Community-acquired pneumonia|community-acquired pneumonias]] due to respiratory viruses, [[pneumococcus]], [[Legionella spp.|legionella]], [[influenza]], or [[listeria monocytogenes]].  
* Colonization with [[Methicillin-resistant staphylococcus aureus|methicillin-resistant Staphylococcus aureus]] or [[Vancomycin-resistant Staphylococcus aureus|vancomycin-resistant Enterococcus]] can lead to posttransplant infection with these organisms.<ref name="pmid18557723">{{cite journal| author=Russell DL, Flood A, Zaroda TE, Acosta C, Riley MM, Busuttil RW et al.| title=Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients. | journal=Am J Transplant | year= 2008 | volume= 8 | issue= 8 | pages= 1737-43 | pmid=18557723 | doi=10.1111/j.1600-6143.2008.02304.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18557723  }}</ref>


== Prevention and treatment ==
== Prevention and treatment ==
* Screening potential liver donors and recipients for infection.<ref name="pmid24528498">{{cite journal| author=Fishman JA| title=From the classic concepts to modern practice. | journal=Clin Microbiol Infect | year= 2014 | volume= 20 Suppl 7 | issue=  | pages= 4-9 | pmid=24528498 | doi=10.1111/1469-0691.12593 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24528498  }}</ref>  
Methods of infection prevention in LT patients:<ref name="pmid24528498">{{cite journal| author=Fishman JA| title=From the classic concepts to modern practice. | journal=Clin Microbiol Infect | year= 2014 | volume= 20 Suppl 7 | issue=  | pages= 4-9 | pmid=24528498 | doi=10.1111/1469-0691.12593 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24528498  }}</ref><ref name="pmid124908042">{{cite journal| author=Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S| title=Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient. | journal=Transplantation | year= 2002 | volume= 74 | issue= 11 | pages= 1645-7 | pmid=12490804 | doi=10.1097/01.TP.0000038746.35254.A4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12490804  }}</ref>
* Appropriate vaccinations before transplantation since antirejection immunosuppressive medications may prevent optimal responses to vaccination post-transplantation.<ref name="pmid124908042">{{cite journal| author=Talbot TR, Hatcher J, Davis SF, Pierson RN, Barton R, Dummer S| title=Scedosporium apiospermum pneumonia and sternal wound infection in a heart transplant recipient. | journal=Transplantation | year= 2002 | volume= 74 | issue= 11 | pages= 1645-7 | pmid=12490804 | doi=10.1097/01.TP.0000038746.35254.A4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12490804  }}</ref>  
* [[Screening (medicine)|Screening]] potential liver donors and recipients for infection
* 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.  
* Appropriate [[vaccinations]] before transplantation
* Certain [[vaccines]] such as [[pneumococcal]] and [[Influenza vaccine|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.
 
==== Bacterial infection ====
* Empiric [[broad-spectrum antibiotics]] should be initiated if a bacterial infection is suspected in a liver transplant recipient until the specific bacterium and its sensitivities can be identified.
* Antibiotic regimens should include coverage for [[gram-positive cocci]], [[gram-negative bacilli]] and [[anaerobes]]. 
* The bloodstream, surgical wounds, and the urinary tract are common sites for primary infection, which may then disseminate.<ref name="pmid27365388">{{cite journal| author=Patterson TF, Thompson GR, Denning DW, Fishman JA, Hadley S, Herbrecht R et al.| title=Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2016 | volume= 63 | issue= 4 | pages= e1-e60 | pmid=27365388 | doi=10.1093/cid/ciw326 | pmc=4967602 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27365388  }}</ref>
* [[Clostridium difficile infection|Clostridium difficile colitis]] can also occur, particularly in the early period following transplantation and in patients requiring prolonged hospitalization. Liver transplantation has been identified as a significant risk factor for [[Clostridium difficile infection|C. difficile]] infection in the hospital.<ref name="pmid8161624">{{cite journal| author=Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW| title=Clostridium difficile colonization and diarrhea at a tertiary care hospital. | journal=Clin Infect Dis | year= 1994 | volume= 18 | issue= 2 | pages= 181-7 | pmid=8161624 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8161624  }}</ref>
* [[Pseudomonas aeruginosa]] and [[enterobacter]] species may be recovered from [[bronchoalveolar lavage]] specimens.
* Other common bacterial pathogens associated with [[pneumonia]] include [[Staphylococcus aureus]], [[Klebsiella pneumoniae|Klebsiella pneumonia]], [[Stenotrophomonas maltophilia]], and [[Citrobacter freundii]].


==== Pneumocystis jirovecii  ====
==== 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.<ref name="pmid23465020">{{cite journal| author=Martin SI, Fishman JA, AST Infectious Diseases Community of Practice| title=Pneumocystis pneumonia in solid organ transplantation. | journal=Am J Transplant | year= 2013 | volume= 13 Suppl 4 | issue=  | pages= 272-9 | pmid=23465020 | doi=10.1111/ajt.12119 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23465020 }}</ref>
* [[Antibiotics]] are administered at transplantation in an attempt to prevent SSIs, including wound and intraabdominal infection.<ref name="pmid23465020">{{cite journal| author=Martin SI, Fishman JA, AST Infectious Diseases Community of Practice| title=Pneumocystis pneumonia in solid organ transplantation. | journal=Am J Transplant | year= 2013 | volume= 13 Suppl 4 | issue=  | pages= 272-9 | pmid=23465020 | doi=10.1111/ajt.12119 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23465020  }}</ref>  
* 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.<ref name="pmid9624195">{{cite journal| author=Fishman JA, Rubin RH| title=Infection in organ-transplant recipients. | journal=N Engl J Med | year= 1998 | volume= 338 | issue= 24 | pages= 1741-51 | pmid=9624195 | doi=10.1056/NEJM199806113382407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9624195 }}</ref>  


* In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation.
* In patients without [[sulfonamide]] [[allergy]], [[Sulfamethoxazole-Trimethoprim|trimethoprim-sulfamethoxazole]] is generally administered for 6 to 12 months after liver transplantation to reduce the risk of [[pneumocystis jirovecii]] [[pneumonia]], [[listeria monocytogenes]], [[nocardia]], and [[toxoplasma gondii]].<ref name="pmid27682069">{{cite journal| author=Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G et al.| title=Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. | journal=Clin Infect Dis | year= 2017 | volume= 64 | issue= 1 | pages= 87-91 | pmid=27682069 | doi=10.1093/cid/ciw668 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27682069  }}</ref><ref name="pmid9624195">{{cite journal| author=Fishman JA, Rubin RH| title=Infection in organ-transplant recipients. | journal=N Engl J Med | year= 1998 | volume= 338 | issue= 24 | pages= 1741-51 | pmid=9624195 | doi=10.1056/NEJM199806113382407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9624195 }}</ref>
* 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.<ref name="pmid27682069">{{cite journal| author=Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G et al.| title=Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. | journal=Clin Infect Dis | year= 2017 | volume= 64 | issue= 1 | pages= 87-91 | pmid=27682069 | doi=10.1093/cid/ciw668 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27682069  }}</ref>
* One single-strength tablet is taken daily or one double-strength tablet is taken three times weekly.  
* 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 (medicine)|side effect]] of [[Sulfamethoxazole-Trimethoprim|trimethoprim-sulfamethoxazole]] is [[allergy]] and [[myelosuppression]].
* 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.<ref name="pmid16382458">{{cite journal| author=Park JM, Lake KD, Arenas JD, Fontana RJ| title=Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients. | journal=Liver Transpl | year= 2006 | volume= 12 | issue= 1 | pages= 112-6 | pmid=16382458 | doi=10.1002/lt.20562 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16382458 }}</ref>
* As a result, the incidence of CMV disease in the posttransplant setting has declined.<ref name="pmid15023154">{{cite journal| author=Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B et al.| title=Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. | journal=Am J Transplant | year= 2004 | volume= 4 | issue= 4 | pages= 611-20 | pmid=15023154 | doi=10.1111/j.1600-6143.2004.00382.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15023154  }}</ref>


==== Cytomegalovirus ====
==== Cytomegalovirus (CMV) ====
* 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.  
* Liver transplant recipients who are seronegative for [[Cytomegalovirus infection|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.
* [[Cytomegalovirus infection|CMV]]-seropositive recipients have a modest risk.
* CMV D-/R- recipients have the lowest risk. [36]
* CMV-seronegative recipients have the lowest risk.<ref name="pmid25152570">{{cite journal| author=Marcelin JR, Beam E, Razonable RR| title=Cytomegalovirus infection in liver transplant recipients: updates on clinical management. | journal=World J Gastroenterol | year= 2014 | volume= 20 | issue= 31 | pages= 10658-67 | pmid=25152570 | doi=10.3748/wjg.v20.i31.10658 | pmc=4138447 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152570  }}</ref>
* CMV infection has been associated with an accelerated course of hepatitis C virus recurrence. [41,42].  
* CMV infection has been associated with an accelerated course of [[hepatitis C virus]] recurrence.<ref name="pmid12355385">{{cite journal| author=Razonable RR, Burak KW, van Cruijsen H, Brown RA, Charlton MR, Smith TF et al.| title=The pathogenesis of hepatitis C virus is influenced by cytomegalovirus. | journal=Clin Infect Dis | year= 2002 | volume= 35 | issue= 8 | pages= 974-81 | pmid=12355385 | doi=10.1086/342911 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12355385  }}</ref>
* '''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]
* As a result, the incidence of CMV disease in the post-transplant setting has declined.<ref name="pmid15023154">{{cite journal| author=Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B et al.| title=Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. | journal=Am J Transplant | year= 2004 | volume= 4 | issue= 4 | pages= 611-20 | pmid=15023154 | doi=10.1111/j.1600-6143.2004.00382.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15023154  }}</ref>
* '''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
* '''Prophylaxis''': [[Ganciclovir]] and [[valganciclovir]] are used to prevent CMV infection in patients at risk of CMV reactivation for three to six months.<ref name="pmid18094380">{{cite journal| author=Fishman JA| title=Infection in solid-organ transplant recipients. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 25 | pages= 2601-14 | pmid=18094380 | doi=10.1056/NEJMra064928 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18094380  }}</ref><ref name="pmid16382458">{{cite journal| author=Park JM, Lake KD, Arenas JD, Fontana RJ| title=Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients. | journal=Liver Transpl | year= 2006 | volume= 12 | issue= 1 | pages= 112-6 | pmid=16382458 | doi=10.1002/lt.20562 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16382458  }}</ref>
* CMV [[prophylaxis]] reduced the risk of biopsy-proven [[Transplant rejection|rejection]] in liver transplant recipients.<ref name="pmid16315314">{{cite journal| author=Slifkin M, Ruthazer R, Freeman R, Bloom J, Fitzmaurice S, Fairchild R et al.| title=Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation. | journal=Liver Transpl | year= 2005 | volume= 11 | issue= 12 | pages= 1597-602 | pmid=16315314 | doi=10.1002/lt.20523 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16315314 }}</ref>
* '''Treatment''': [[Valganciclovir]], at doses of 900 mg daily is the main drug for treatment.<ref name="pmid23896556">{{cite journal| author=Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L et al.| title=Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. | journal=Transplantation | year= 2013 | volume= 96 | issue= 4 | pages= 333-60 | pmid=23896556 | doi=10.1097/TP.0b013e31829df29d | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23896556  }}</ref>


==== Candida ====
==== Candida ====
* Candida is the predominant fungal infection encountered after liver transplantation [56].  
* Candida is the predominant [[fungal infection]] encountered after liver transplantation.  
* Candida prophylaxis for adult liver transplant recipients with ≥2 of the following risk factors [57]:
* Candida [[prophylaxis]] for adult liver transplant recipients with ≥2 of the following risk factors include:<ref name="pmid12829905">{{cite journal| author=Husain S, Tollemar J, Dominguez EA, Baumgarten K, Humar A, Paterson DL et al.| title=Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients: prospective, multicenter, case-controlled study. | journal=Transplantation | year= 2003 | volume= 75 | issue= 12 | pages= 2023-9 | pmid=12829905 | doi=10.1097/01.TP.0000065178.93741.72 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12829905  }}</ref>
* Prolonged or repeat operation
* Prolonged or repeat operation
* Retransplantation
* Retransplantation
* Renal failure
* [[Renal insufficiency|Renal failure]]
* High transfusion requirement
* High transfusion requirement
* Choledochojejunostomy
* Choledochojejunostomy
* Candida colonization during the perioperative period
* [[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.
* Prophylaxis: [[Fluconazole]] 400 mg orally daily is the drug of choice for one to four weeks or for as long as risk factors persist.


==== Aspergillus ====
==== Aspergillus ====
* Aspergillus infections occur in patients with certain risk factors.  
* [[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].  
* Risk factors for [[Aspergillus]] infection after liver transplantation include [[fulminant hepatic failure]], reoperation, retransplantation, renal or [[hepatic failure]], [[cytomegalovirus infection]], [[hepatitis C infection]], and high-dose [[glucocorticoids]].  
* Prophylaxis: fluconazole prophylaxis decreased invasive fungal infections by 75 percent. [66].
* Mortality of [[aspergillosis]] in early series of liver transplant recipients approached 100 percent.<ref name="pmid25348192">{{cite journal| author=Barchiesi F, Mazzocato S, Mazzanti S, Gesuita R, Skrami E, Fiorentini A et al.| title=Invasive aspergillosis in liver transplant recipients: epidemiology, clinical characteristics, treatment, and outcomes in 116 cases. | journal=Liver Transpl | year= 2015 | volume= 21 | issue= 2 | pages= 204-12 | pmid=25348192 | doi=10.1002/lt.24032 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25348192  }}</ref>
* The most common site of aspergillosis is the lung, although it may disseminate to other sites including the central nervous system (CNS).  
* [[Nosocomial pneumonia|Nosocomial pneumonias]] are particularly frequent in patients who require prolonged mechanical ventilation.  
* It is the most common cause of CNS infection in liver transplant recipients, accounting for 55 percent of brain abscesses in one series [99].  
* The most common site of [[aspergillosis]] is the [[lung]].  
* 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].  
* It is the most common cause of [[CNS infection]] in liver transplant recipients, accounting for 55 percent of [[brain abscesses]].<ref name="pmid9884245">{{cite journal| author=Bonham CA, Dominguez EA, Fukui MB, Paterson DL, Pankey GA, Wagener MM et al.| title=Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management. | journal=Transplantation | year= 1998 | volume= 66 | issue= 12 | pages= 1596-604 | pmid=9884245 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9884245  }}</ref>
** Other types
* Prophylaxis: [[Fluconazole]] prophylaxis decreased invasive fungal infections by 75 percent.<ref name="pmid16912905">{{cite journal| author=Playford EG, Webster AC, Sorrell TC, Craig JC| title=Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients. | journal=Eur J Clin Microbiol Infect Dis | year= 2006 | volume= 25 | issue= 9 | pages= 549-61 | pmid=16912905 | doi=10.1007/s10096-006-0182-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16912905 }}</ref><ref name="pmid2829792">{{cite journal| author=Colonna JO, Winston DJ, Brill JE, Goldstein LI, Hoff MP, Hiatt JR et al.| title=Infectious complications in liver transplantation. | journal=Arch Surg | year= 1988 | volume= 123 | issue= 3 | pages= 360-4 | pmid=2829792 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2829792  }}</ref>
* 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 ===
=== 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.  
* [[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 [8].  
* These patients usually develop the same types of community-acquired infections seen in the general population, although at an increased rate.<ref name="pmid180943802">{{cite journal| author=Fishman JA| title=Infection in solid-organ transplant recipients. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 25 | pages= 2601-14 | pmid=18094380 | doi=10.1056/NEJMra064928 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18094380  }}</ref>
* 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]
* 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.
* 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 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].
* 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.<ref name="pmid26094550">{{cite journal| author=Galante A, Pischke S, Polywka S, Luetgehethmann M, Suneetha PV, Gisa A et al.| title=Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting. | journal=Transpl Infect Dis | year= 2015 | volume= 17 | issue= 4 | pages= 617-22 | pmid=26094550 | doi=10.1111/tid.12411 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26094550  }}</ref>
* Chronic [[viral infections]] such as [[Hepatitis B virus|HBV]] and [[HCV infection|HCV]] can also produce damage to the liver [[allograft]].
* Secondary [[Tumor|tumors]] can occur also, especially posttransplant [[Lymphoproliferative disorders|lymphoproliferative disease]] due to [[Epstein Barr virus|EBV]] and [[hepatocellular carcinoma]] due to [[Hepatitis B virus|HBV]] or [[Hepatitis C|HCV]].
* [[Hepatitis E|Hepatitis E virus]] can also cause [[chronic hepatitis]] in liver transplant recipients and should be considered in patients with unexplained [[Liver function tests|liver enzyme]] elevations.<ref name="pmid14966414">{{cite journal| author=Kumar D, Prasad GV, Zaltzman J, Levy GA, Humar A| title=Community-acquired West Nile virus infection in solid-organ transplant recipients. | journal=Transplantation | year= 2004 | volume= 77 | issue= 3 | pages= 399-402 | pmid=14966414 | doi=10.1097/01.TP.0000101435.91619.31 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14966414  }}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 17:38, 6 January 2018


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

Liver trasnsplantation Microchapters

Home

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

Infection is the most frequent cause of death following liver transplantation. According to the timing, infection can be divided into three sections; First month after transplantation, 1 to 6 months after transplantation, and more than 6 to 12 months after transplantation. Prevention of infection includes Screening potential liver donors and recipients for infection, certain vaccines such as pneumococcal and influenza vaccines should be repeated after transplantation in an attempt to lower the risk for these diseases. Empiric broad-spectrum antibiotics should be initiated if a bacterial infection is suspected in a liver transplant recipient until the specific bacterium and its sensitivities can be identified. Antibiotic regimens should include coverage for gram-positive cocci, gram-negative bacilli and anaerobes. In patients without sulfonamide allergy, trimethoprim-sulfamethoxazole is generally administered for 6 to 12 months after liver transplantation to reduce the risk of pneumocystis jirovecii pneumonia, listeria monocytogenes, nocardia, and toxoplasma gondii. Prophylaxis of CMV includes Ganciclovir and valganciclovir are used to prevent CMV infection in patients at risk of CMV reactivation for three to six months. Prophylaxis of candida includes Fluconazole 400 mg orally daily is the drug of choice for one to four weeks or for as long as risk factors persist. Prophylaxis of aspergillosis includes Fluconazole prophylaxis decreased invasive fungal infections by 75 percent.

Liver transplantation infection

Timing of infection

First month after transplantation

  • Endemic infections should be considered in the differential diagnosis of post-transplant infection.

1 to 6 months after transplantation

Major infections due to opportunistic pathogens include:

More than 6 to 12 months after transplantation

Prevention and treatment

Methods of infection prevention in LT patients:[10][11]

  • Screening potential liver donors and recipients for infection
  • Appropriate vaccinations before transplantation
  • 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.

Bacterial infection

Pneumocystis jirovecii

  • Antibiotics are administered at transplantation in an attempt to prevent SSIs, including wound and intraabdominal infection.[14]

Cytomegalovirus (CMV)

  • 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-seronegative recipients have the lowest risk.[17]
  • CMV infection has been associated with an accelerated course of hepatitis C virus recurrence.[18]
  • As a result, the incidence of CMV disease in the post-transplant setting has declined.[19]
  • Prophylaxis: Ganciclovir and valganciclovir are used to prevent CMV infection in patients at risk of CMV reactivation for three to six months.[20][21]
  • CMV prophylaxis reduced the risk of biopsy-proven rejection in liver transplant recipients.[22]
  • Treatment: Valganciclovir, at doses of 900 mg daily is the main drug for treatment.[23]

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 include:[24]
  • 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 for one to four weeks or for as long as risk factors persist.

Aspergillus

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.
  7. ↑ Bocchi EA, Bellotti G, Mocelin AO, Uip D, Bacal F, Higuchi ML; et al. (1996). "Heart transplantation for chronic Chagas' heart disease". Ann Thorac Surg. 61 (6): 1727–33. doi:10.1016/0003-4975(96)00141-5. PMID 8651775.
  8. ↑ Fernàndez-Sabé N, Cervera C, Fariñas MC, Bodro M, Muñoz P, Gurguí M; et al. (2012). "Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: a matched case-control study". Clin Infect Dis. 54 (3): 355–61. doi:10.1093/cid/cir806. PMID 22075795.
  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. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ Fishman JA, Rubin RH (1998). "Infection in organ-transplant recipients". N Engl J Med. 338 (24): 1741–51. doi:10.1056/NEJM199806113382407. PMID 9624195.
  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. ↑ 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.
  20. ↑ Fishman JA (2007). "Infection in solid-organ transplant recipients". N Engl J Med. 357 (25): 2601–14. doi:10.1056/NEJMra064928. PMID 18094380.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  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. ↑ 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.
  27. ↑ 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.
  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.
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