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August 1992, Vol 146, No. 8 >
Article | August 1992

Patterns of Infection After Pediatric Liver Transplantation FREE

David L. George, MD; Paul M. Arnow, MD; Amy Fox, MD; J. Richard Thistlethwaite, MD; Jean C. Emond, MD; Christoph E. Broelsch, MD; Peter F. Whitington, MD
[+] Author Affiliations

Accepted for publication January 27, 1992.

Reprint requests to Section of Infectious Diseases, The University of Chicago Medical Center, 5841 S Maryland Ave, Box 11, Chicago, IL 60637 (Dr Arnow).


Am J Dis Child. 1992;146(8):924-929. doi:10.1001/archpedi.1992.02160200046024.
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• Objective.  —To characterize the patterns of infection that occur after orthotopic liver transplantation in children.

Design.  —Inception cohort, retrospective.

Setting.  —Referral center for liver transplantation, university hospital.

Patients.  —Thirty-six consecutive children who underwent orthotopic liver transplantation and who survived for at least 48 hours after transplantation.

Interventions.  —None.

Measurements and Results.  —Twenty-six (72%) of the children had at least one infection, and infection caused four deaths. More infections occurred when prophylactic antilymphocyte antibodies were given than when they were not given (2.9 vs 1.0 infections per transplant). The risk of infection was greatest during the first 2 weeks after orthotopic liver transplantation. Most infections were caused by bacteria (52 cases), followed by viruses (16 cases) and fungi (11 cases). Bacteria were the most common pathogens during all periods, except the third and fourth weeks, when viruses predominated. The most common primary sites of bacterial infection were abdomen (15 cases), bloodstream (15 cases), and surgical wound (10 cases); the most frequent isolates were aerobic gram-negative bacilli (48% of isolates) and enterococci (19%). Cytomegalovirus was the most common viral pathogen (seven cases), and Candida albicans caused all fungal infections. Fungal infections were significantly associated with systemic antibiotic therapy and abdominal complications.

Conclusions.  —Characteristic patterns of infection occur after pediatric orthotopic liver transplantation, and knowledge of these patterns is likely to result in improved care for transplant recipients.(AJDC. 1992;146:924-929)

REFERENCES

1 +
Fulginiti VA, Scribner R, Groth CG, et al.  Infections in recipients of liver homografts . N Engl J Med . 1968;;179:619-626.
2 +
Busuttil RW, Colonna JO, Hiatt JR, et al.  The first 100 liver transplants at UCLA . Ann Surg . 1987;;206:387-399.
3 +
Krom RAF, Wiesner RH, Rettke SR, et al.  The first 100 liver transplantations at the Mayo Clinic . Mayo Clin Proc . 1989;;64:84-94.
4 +
Iwatsuki S, Starzl TE, Gordon RD, et al.  Experience in 1,000 liver transplants under cyclosporine-steroid therapy: a survival report . Transplant Proc . 1988;;20:498-504.
5 +
Colonna JO, Winston DJ, Brill JE, et al.  Infectious complications in liver transplantation . Arch Surg . 1988;;123:360-364.
6 +
Dummer JS, Hardy A, Poorsattar A, Ho M.  Early infections in kidney, heart, and liver transplant recipients on cyclosporine . Transplantation . 1983;;36:259-267.
7 +
George D, Arnow P, Fox A, et al.  Infections complicating liver transplantation . Hepatology . 1988;;8:1286. Abstract.
8 +
Kusne S, Dummer JS, Singh N, et al.  Infections after liver transplantation: an analysis of 101 consecutive cases . Medicine . 1988;;67:132-143.
9 +
Paya CV, Hermans PE, Washington JA, et al.  Incidence, distribution and outcome of episodes of infection in 100 orthotopic liver transplantations . Mayo Clin Proc . 1989;;64:555-564.
10 +
Millis JM, Brems JJ, Hiatt JR, et al.  Orthotopic liver transplantation for biliary atresia: evolution of management . Arch Surg . 1988;;123:1237-1239.
11 +
Cuervas-Mons V, Rimola A, Van Thiel DH, Gavaler JS, Schade RR, Starzl TE.  Does previous abdominal surgery alter the outcome of pediatric patients subjected to orthotopic liver transplantations? Gastroenterology . 1986;;90:853-857.
12 +
Broelsch CE, Emond JC, Thistlethwaite JR, et al.  Liver transplantation, including the concept of reduced-size liver transplants in children . Ann Surg . 1988;;208:410-419.
13 +
Lerut J, Gordon RD, Iwatsuki S, et al.  Biliary tract complications in human orthotopic liver transplantation . Transplantation . 1987;;43:45-51.
14 +
Esquivel CO, Koneru B, Karrer F, et al.  Liver transplantation before 1 year of age . J Pediatr . 1987;;110:545-548.
15 +
Makowka L, Steiber AC, Sher L, et al.  Surgical techniques of orthotopic liver transplantation . Gastroenterol Clin North Am . 1988;;17:33-51.
16 +
Breinig MK, Zitelli B, Starzl TE, Ho M.  Epstein-Barr virus, cytomegalovirus, and other viral infections in children after liver transplantation . J Infect Dis . 1987;;156:273-279.
17 +
Singh N, Dummer JS, Kusne S, et al.  Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies . J Infect Dis . 1988;;158: 124-131.
18 +
Ho M, Jaffe R, Miller G, et al.  The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children . Transplantation . 1988;;45:719-727.
19 +
Koneru B, Jaffe R, Esquivel CO, et al.  Adenoviral infections in pediatric liver transplant recipients . JAMA . 1987;;258:489-492.
20 +
McGregor RS, Zitelli BJ, Urbach AH, Malatack JJ, Gartner JC.  Varicella in pediatric orthotopic liver transplant recipients . Pediatrics . 1989;;83: 256-261.
21 +
King SM, Petric M, Superina R, Graham N, Roberts EA.  Cytomegalovirus infections in pediatric liver transplantation . AJDC . 1990;;144:1307-1310.
22 +
Salt A, Sutehall G, Sargaison M, et al.  Viral and Toxoplasma gondii infections in children after liver transplantation . J Clin Pathol . 1990;;43:63-67.
23 +
Bowman JS, Green M, Scantlebury VP, et al.  OKT3 and viral disease in pediatric liver transplant recipients . Clin Transplantation . 1991;;5:294-300.
24 +
Starzl TE, Iwatsuki S, Van Thiel DH, et al.  Evolution of liver transplantation . Hepatology . 1982;;2:614-636.
25 +
Garner JS, Jarvis WR, Emori TC, Horan TC, Hughes JM.  CDC definitions for nosocomial infections, 1988 . J Infect Control . 1988;;16:128-140.
26 +
Delage G, Brochu P, Robillard L, Jasmin G, Joncas JH, Lapointe N.  Giant cell pneumonia due to respiratory syncytial virus . Arch Pathol Lab Med . 1984;;108:623-625.
27 +
Alonso EM, Fox AS, Franklin WA, Whitington PF.  Postnecrotic cirrhosis following varicella hepatitis in a liver transplant patient . Transplantation . 1990;;49:650-653.
28 +
Onderdonk AB, Markham RB, Zeleznik DF, et al.  Evidence for T cell-dependent immunity to Bacteroides fragilis in an intraabdominal abscess model . J Clin Invest . 1982;;69:9-16.
29 +
Powderly WG, Schreiber JR, Pier GB, et al.  T Cells recognizing polysaccharide-specific B cells function as contrasuppressor cells in the generation of T cell immunity to Pseudomonas aeruginosa . J Immunol . 1988;; 140:2746-2752.
30 +
Andrews W, Fyock B, Gray S, et al.  Pediatric liver transplantation: the Dallas experience . Transplant Proc . 1987;;19:3267-3276.
31 +
Zitelli BJ, Gartner JC, Malatack JJ, et al.  Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation . Transplant Proc . 1987;;19:3309-3316.
32 +
Ascher NL, Stock PG, Bumgardner GL, Payne WD, Najarian JS.  Infection and rejection of primary hepatic transplant in 93 consecutive patients treated with triple immunosuppressive therapy . Surg Gynecol Obstet . 1988;; 167:474-484.
33 +
Rubin RH, Wolfson JS, Cosimi AB, Tolkoff-Rubin NE.  Infection in the renal transplant recipient . Am J Med . 1981;;70:405-411.
34 +
George DL, Arnow PM, Fox AS, et al.  Bacterial infection as a complication of liver transplantation: epidemiology and risk factors . Rev Infect Dis . 1991;;13:387-396.
35 +
Klein RB, Fischer TJ, Gard SE, Biberstein M, Rich KC, Stiehm ER.  Decreased mononuclear and polymorphonuclear chemotaxis in human newborns, infants, and young children . Pediatrics . 1977;;60:467-472.
36 +
Hau T, Hoffman R, Simmons RL.  Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis, I: in vivo inhibition of peritoneal leukocytosis . Surgery . 1978;;83:223-229.
37 +
Onderdonk AB, Bartlett JG, Louie T, Sullivan-Siegler N, Gorbach SL.  Microbial synergy in experimental intraabdominal abscesses . Infect Immun . 1976;;13:22-26.
38 +
Weinstein WM, Onderdonk AB, Bartlett JG, Louie TL, Gorbach SL.  Antimicrobial therapy of experimental intraabdominal sepsis . J Infect Dis . 1975;;132:282-286.
39 +
Esquivel CO, Iwatsuki S, Gordon RD, et al.  Indications for pediatric liver transplantation . J Pediatr . 1987;;111:1039-1045.
40 +
Houssin D, Ortega D, Richardson A, et al.  Mycotic aneurysm of the hepatic artery complicating human liver transplantation . Transplantation . 1988;;46:469-472.
41 +
Zajko AB, Bradshaw JR, Marsh JW.  Mycotic pseudoaneurysm of the gastroduodenal artery: an unusual cause of lower gastrointestinal tract hemorrhage following liver transplantation . Transplantation . 1988;;45:990-991.
42 +
Kaplan LJ, Daum RS, Smaron M, McCarthy CA.  Severe measles in immunocompromised patients . JAMA . 1992;;267:1237-1241.
43 +
Dummer JS, White LT, Ho M, Griffith BP, Hardesty L, Bahnson HT.  Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who received cyclosporine . J Infect Dis . 1985;;152:1182-1191.
44 +
Johnson PC, Lewis RM, Golden DL, et al.  The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression . Transplantation . 1988;;45:116-121.
45 +
Weir MR, Irwin BC, Maters AW, et al.  Incidence of cytomegalovirus disease in cyclosporine-treated renal transplant recipients based on donor/recipient pre-transplant immunity . Transplantation . 1987;;43:187-193.
46 +
Snydman DR, Werner BG, Heinze-Lacey B, et al.  Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renaltransplant recipients . N Engl J Med . 1987;;317:1049-1054.
47 +
Saliba F, Arulnaden JL, Gugenheim J, et al.  CMV hyperimmune globulin prophylaxis after liver transplantation: a prospective randomized controlled study . Transplant Proc . 1989;;21:2260-2262.
48 +
Plotkin SA, Starr SE, Friedman HM, et al.  Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant: a controlled trial . Ann Intern Med . 1991;;114:525-531.
49 +
Balfour HH, Chace BA, Stapleton JT, Simmons RL, Fryd DS.  A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts . N Engl J Med . 1989;; 320:1381-1387.
50 +
Schmidt GM, Horak DA, Niland JC, et al.  A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants . N Engl J Med . 1991;;324: 1005-1111.

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References

1 +
Fulginiti VA, Scribner R, Groth CG, et al.  Infections in recipients of liver homografts . N Engl J Med . 1968;;179:619-626.
2 +
Busuttil RW, Colonna JO, Hiatt JR, et al.  The first 100 liver transplants at UCLA . Ann Surg . 1987;;206:387-399.
3 +
Krom RAF, Wiesner RH, Rettke SR, et al.  The first 100 liver transplantations at the Mayo Clinic . Mayo Clin Proc . 1989;;64:84-94.
4 +
Iwatsuki S, Starzl TE, Gordon RD, et al.  Experience in 1,000 liver transplants under cyclosporine-steroid therapy: a survival report . Transplant Proc . 1988;;20:498-504.
5 +
Colonna JO, Winston DJ, Brill JE, et al.  Infectious complications in liver transplantation . Arch Surg . 1988;;123:360-364.
6 +
Dummer JS, Hardy A, Poorsattar A, Ho M.  Early infections in kidney, heart, and liver transplant recipients on cyclosporine . Transplantation . 1983;;36:259-267.
7 +
George D, Arnow P, Fox A, et al.  Infections complicating liver transplantation . Hepatology . 1988;;8:1286. Abstract.
8 +
Kusne S, Dummer JS, Singh N, et al.  Infections after liver transplantation: an analysis of 101 consecutive cases . Medicine . 1988;;67:132-143.
9 +
Paya CV, Hermans PE, Washington JA, et al.  Incidence, distribution and outcome of episodes of infection in 100 orthotopic liver transplantations . Mayo Clin Proc . 1989;;64:555-564.
10 +
Millis JM, Brems JJ, Hiatt JR, et al.  Orthotopic liver transplantation for biliary atresia: evolution of management . Arch Surg . 1988;;123:1237-1239.
11 +
Cuervas-Mons V, Rimola A, Van Thiel DH, Gavaler JS, Schade RR, Starzl TE.  Does previous abdominal surgery alter the outcome of pediatric patients subjected to orthotopic liver transplantations? Gastroenterology . 1986;;90:853-857.
12 +
Broelsch CE, Emond JC, Thistlethwaite JR, et al.  Liver transplantation, including the concept of reduced-size liver transplants in children . Ann Surg . 1988;;208:410-419.
13 +
Lerut J, Gordon RD, Iwatsuki S, et al.  Biliary tract complications in human orthotopic liver transplantation . Transplantation . 1987;;43:45-51.
14 +
Esquivel CO, Koneru B, Karrer F, et al.  Liver transplantation before 1 year of age . J Pediatr . 1987;;110:545-548.
15 +
Makowka L, Steiber AC, Sher L, et al.  Surgical techniques of orthotopic liver transplantation . Gastroenterol Clin North Am . 1988;;17:33-51.
16 +
Breinig MK, Zitelli B, Starzl TE, Ho M.  Epstein-Barr virus, cytomegalovirus, and other viral infections in children after liver transplantation . J Infect Dis . 1987;;156:273-279.
17 +
Singh N, Dummer JS, Kusne S, et al.  Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT3 antibodies . J Infect Dis . 1988;;158: 124-131.
18 +
Ho M, Jaffe R, Miller G, et al.  The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children . Transplantation . 1988;;45:719-727.
19 +
Koneru B, Jaffe R, Esquivel CO, et al.  Adenoviral infections in pediatric liver transplant recipients . JAMA . 1987;;258:489-492.
20 +
McGregor RS, Zitelli BJ, Urbach AH, Malatack JJ, Gartner JC.  Varicella in pediatric orthotopic liver transplant recipients . Pediatrics . 1989;;83: 256-261.
21 +
King SM, Petric M, Superina R, Graham N, Roberts EA.  Cytomegalovirus infections in pediatric liver transplantation . AJDC . 1990;;144:1307-1310.
22 +
Salt A, Sutehall G, Sargaison M, et al.  Viral and Toxoplasma gondii infections in children after liver transplantation . J Clin Pathol . 1990;;43:63-67.
23 +
Bowman JS, Green M, Scantlebury VP, et al.  OKT3 and viral disease in pediatric liver transplant recipients . Clin Transplantation . 1991;;5:294-300.
24 +
Starzl TE, Iwatsuki S, Van Thiel DH, et al.  Evolution of liver transplantation . Hepatology . 1982;;2:614-636.
25 +
Garner JS, Jarvis WR, Emori TC, Horan TC, Hughes JM.  CDC definitions for nosocomial infections, 1988 . J Infect Control . 1988;;16:128-140.
26 +
Delage G, Brochu P, Robillard L, Jasmin G, Joncas JH, Lapointe N.  Giant cell pneumonia due to respiratory syncytial virus . Arch Pathol Lab Med . 1984;;108:623-625.
27 +
Alonso EM, Fox AS, Franklin WA, Whitington PF.  Postnecrotic cirrhosis following varicella hepatitis in a liver transplant patient . Transplantation . 1990;;49:650-653.
28 +
Onderdonk AB, Markham RB, Zeleznik DF, et al.  Evidence for T cell-dependent immunity to Bacteroides fragilis in an intraabdominal abscess model . J Clin Invest . 1982;;69:9-16.
29 +
Powderly WG, Schreiber JR, Pier GB, et al.  T Cells recognizing polysaccharide-specific B cells function as contrasuppressor cells in the generation of T cell immunity to Pseudomonas aeruginosa . J Immunol . 1988;; 140:2746-2752.
30 +
Andrews W, Fyock B, Gray S, et al.  Pediatric liver transplantation: the Dallas experience . Transplant Proc . 1987;;19:3267-3276.
31 +
Zitelli BJ, Gartner JC, Malatack JJ, et al.  Pediatric liver transplantation: patient evaluation and selection, infectious complications, and life-style after transplantation . Transplant Proc . 1987;;19:3309-3316.
32 +
Ascher NL, Stock PG, Bumgardner GL, Payne WD, Najarian JS.  Infection and rejection of primary hepatic transplant in 93 consecutive patients treated with triple immunosuppressive therapy . Surg Gynecol Obstet . 1988;; 167:474-484.
33 +
Rubin RH, Wolfson JS, Cosimi AB, Tolkoff-Rubin NE.  Infection in the renal transplant recipient . Am J Med . 1981;;70:405-411.
34 +
George DL, Arnow PM, Fox AS, et al.  Bacterial infection as a complication of liver transplantation: epidemiology and risk factors . Rev Infect Dis . 1991;;13:387-396.
35 +
Klein RB, Fischer TJ, Gard SE, Biberstein M, Rich KC, Stiehm ER.  Decreased mononuclear and polymorphonuclear chemotaxis in human newborns, infants, and young children . Pediatrics . 1977;;60:467-472.
36 +
Hau T, Hoffman R, Simmons RL.  Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis, I: in vivo inhibition of peritoneal leukocytosis . Surgery . 1978;;83:223-229.
37 +
Onderdonk AB, Bartlett JG, Louie T, Sullivan-Siegler N, Gorbach SL.  Microbial synergy in experimental intraabdominal abscesses . Infect Immun . 1976;;13:22-26.
38 +
Weinstein WM, Onderdonk AB, Bartlett JG, Louie TL, Gorbach SL.  Antimicrobial therapy of experimental intraabdominal sepsis . J Infect Dis . 1975;;132:282-286.
39 +
Esquivel CO, Iwatsuki S, Gordon RD, et al.  Indications for pediatric liver transplantation . J Pediatr . 1987;;111:1039-1045.
40 +
Houssin D, Ortega D, Richardson A, et al.  Mycotic aneurysm of the hepatic artery complicating human liver transplantation . Transplantation . 1988;;46:469-472.
41 +
Zajko AB, Bradshaw JR, Marsh JW.  Mycotic pseudoaneurysm of the gastroduodenal artery: an unusual cause of lower gastrointestinal tract hemorrhage following liver transplantation . Transplantation . 1988;;45:990-991.
42 +
Kaplan LJ, Daum RS, Smaron M, McCarthy CA.  Severe measles in immunocompromised patients . JAMA . 1992;;267:1237-1241.
43 +
Dummer JS, White LT, Ho M, Griffith BP, Hardesty L, Bahnson HT.  Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who received cyclosporine . J Infect Dis . 1985;;152:1182-1191.
44 +
Johnson PC, Lewis RM, Golden DL, et al.  The impact of cytomegalovirus infection on seronegative recipients of seropositive donor kidneys versus seropositive recipients treated with cyclosporine-prednisone immunosuppression . Transplantation . 1988;;45:116-121.
45 +
Weir MR, Irwin BC, Maters AW, et al.  Incidence of cytomegalovirus disease in cyclosporine-treated renal transplant recipients based on donor/recipient pre-transplant immunity . Transplantation . 1987;;43:187-193.
46 +
Snydman DR, Werner BG, Heinze-Lacey B, et al.  Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renaltransplant recipients . N Engl J Med . 1987;;317:1049-1054.
47 +
Saliba F, Arulnaden JL, Gugenheim J, et al.  CMV hyperimmune globulin prophylaxis after liver transplantation: a prospective randomized controlled study . Transplant Proc . 1989;;21:2260-2262.
48 +
Plotkin SA, Starr SE, Friedman HM, et al.  Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant: a controlled trial . Ann Intern Med . 1991;;114:525-531.
49 +
Balfour HH, Chace BA, Stapleton JT, Simmons RL, Fryd DS.  A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts . N Engl J Med . 1989;; 320:1381-1387.
50 +
Schmidt GM, Horak DA, Niland JC, et al.  A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants . N Engl J Med . 1991;;324: 1005-1111.

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