© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273
Case report
Candida arteritis occurring in a liver transplant recipient , C. Sol L. Llado e, M. Bodro, C. Baliellas, N. Sabe, A. Petit, E. Ramos, J. Carratala, J. Fabregat. Candida arteritis occurring in a liver transplant recipient. Transpl Infect Dis 2014: 16: 465–468. All rights reserved Abstract: We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.
L. Llado1, C. Sole1, M. Bodro2, C. Baliellas1, N. Sabe2, A. Petit3, E. Ramos1, J. Carratala2, J. Fabregat1 Liver Transplant Unit, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain, 2Infectious Diseases Department, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain, 3Pathology Department, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain 1
Key words: Candida; infection; liver transplantation; arteritis Correspondence to: Marta Bodro, Infectious Diseases Department, Hospital Universitari de Bellvitge, IDIBELL Research Institute, 08907-L’Hospitalet de Llobregat, Barcelona, Spain Tel: +34 93 260 7625 Fax: +34 93 260 7637 E-mail: [email protected]
Received 17 September 2013, revised 18 November 2013, accepted for publication 18 December 2013 DOI: 10.1111/tid.12218 Transpl Infect Dis 2014: 16: 465–468
Candida arteritis is an uncommon complication in solid organ transplant recipients. The few cases reported to date have been renal transplant patients (1–6). This entity is caused by either hematogenous or local spread of the yeast to the arterial wall leading to an intense inflammatory response and, as a consequence, the formation of an aneurysm and destruction of vascular structures. The source of fungal infection is difficult to ascertain because Candida species are normal commensals of the gastrointestinal tract in humans. The source may be donor-to-host transmission or contamination during organ procurement (1, 2). Here, we report the first case of Candida arteritis, to our knowledge, after liver transplantation.
Case report A 63-year-old man with hepatocellular carcinoma underwent surgical liver resection, but because of acute postoperative hepatic failure, an emergency liver transplantation was performed after 24 h of the initial surgery. The donor was an 86-year-old man who died from a vascular stroke and had been hospitalized for 1 day in the intensive care unit, but had not received antibiotic therapy. Blood cultures before procurement were negative. A choledocho-choledochostomy was performed and an arterial anastomosis was made as usual, between the patch from celiac trunk of the donor and the proper
465
Llado et al: Candida arteritis in a liver recipient
hepatic artery of the recipient. The cold ischemia time was 4 h. The immunosuppressive treatment included basiliximab, corticosteroids, and delayed initiation of mycophenolate mofetil and tacrolimus. The recipient received antibiotic prophylaxis with aztreonam and teicoplanin for 24 h. No fungal prophylaxis was administered. He had no history of invasive candidiasis and was not colonized with yeast before transplantation. Five days after transplantation, the preservation media showed Enterobacter cloacae and Enterococcus faecium, but the patient did not receive any antibiotic treatment, because there was no suspicion of infection. No fungus grew in the preservation fluid. The patient then developed a respiratory infection, and piperacillin-tazobactam was prescribed for 8 days. Abdominal ultrasound at 24 h and at 7 days after surgery, performed per protocol at our institution, was normal. He was transferred to the hospital ward after 6 days in the intensive care unit. On postoperative day 14, the patient complained of diffuse abdominal pain. The computed tomography scan showed a pseudoaneurysm in the proper hepatic artery with active bleeding, necessitating immediate operation (Fig. 1). An arterial rupture was found and resection of the affected artery and reconstruction with an arterial graft were performed. Broad-spectrum antibiotics and fluconazole therapy were initiated. Histologic examination of the hepatic artery showed necrohemorrhagic arteritis with abundant yeasts and pseudohyphae in the arterial wall (Fig. 2), subsequently identified as Candida albicans, Candida glabrata, and Candida tropicalis. Blood cultures were negative. Antifungal therapy with intravenous anidulafungin was prescribed for 6 weeks after surgery and then replaced by voriconazole for 4 additional months according to minimum inhibitory concentrations of the Candida species isolated in the arterial tissue (Table 1). Voriconazole serum levels were regularly determined and were within the therapeutic range. Five months after transplantation, the patient was admitted to the hospital for fever and delayed hepatic function. Voriconazole was replaced by anidulafungin because of the suspicion of hepatotoxicity and a computed tomography scan showed dilation of the bile duct. A percutaneous transhepatic cholangiography was performed, and the bile duct obstruction was resolved. However, liver function did not improve. The liver biopsy was unspecific. The patient’s liver function was progressively impaired, and he eventually died 8 months after transplantation. The autopsy analysis of the graft, including cultures and thorough histologic examination of the arterial hepatic graft anastomosis, ruled out fungal infection.
466
Fig. 1. Computed tomography scan showed a pseudoaneurysm (black arrow) in the proper hepatic artery with active bleeding, necessitating immediate operation.
Recipients from the same donor did not develop any complication after transplantation.
Discussion We describe the first case of Candida arteritis in a liver transplant recipient properly cured after surgical management and prolonged antifungal treatment. Candida arteritis usually occurs early after transplantation (1). The source of fungal infection is difficult to ascertain. Donor-to-host transmission has been suggested, although some authors have hypothesized that contamination during graft harvesting and processing is more likely. Albano et al. (2) identified episodes in which there was a close relationship between isolates from preservation fluids and isolates from the operative sites of recipients, so contamination during organ recovery from the donor was assumed. Moreover, among factors that might explain the contamination of the deceased organ donors, digestive tract rupture has been suggested (1, 2). Although transmission of pathogens by donors is a potential cause of infection in transplant recipients, routine microbiologic analysis of the preservation fluid is not well established. Only a few retrospective studies have analyzed the percentage of pathogen transmission from the preservation fluid and it ranges from 0% to 9.8% (7–13). In addition, the post-transplant antibiotic protocol was highly variable, including antifungal therapy in some cases (7–11). In some reports, Candida
Transplant Infectious Disease 2014: 16: 465–468
Llado et al: Candida arteritis in a liver recipient
A
B
Fig. 2. (A) Cross-section panoramic view of the artery with signs of acute arteritis with focal rupture of the arterial wall (arrow). (B) A closer examination highlights transmural necrosis and acute inflammatory infiltrate (hematoxylin–eosin, 49). Inset: Grocott stains identified abundant yeast and pseudohyphae morphologically consistent with Candida species.
Minimum inhibitory concentration (mg/L) of the Candida species isolated in the arterial tissue of the patient
Antifungal agent
Candida albicans
Candida tropicalis
Amphotericin B
0.5
0.5
0.5
Fluconazole
8
0.5
4
Posaconazole
0
0
0
0
Candida glabrata
Voriconazole
0
Anidulafungin
0
Micafungin
0
0
0
Caspofungin
0
0
0
Flucytosine
0.12
0.012
Case report
Candida arteritis occurring in a liver transplant recipient , C. Sol L. Llado e, M. Bodro, C. Baliellas, N. Sabe, A. Petit, E. Ramos, J. Carratala, J. Fabregat. Candida arteritis occurring in a liver transplant recipient. Transpl Infect Dis 2014: 16: 465–468. All rights reserved Abstract: We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.
L. Llado1, C. Sole1, M. Bodro2, C. Baliellas1, N. Sabe2, A. Petit3, E. Ramos1, J. Carratala2, J. Fabregat1 Liver Transplant Unit, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain, 2Infectious Diseases Department, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain, 3Pathology Department, Hospital Universitari de Bellvitge – Institut d’Investigacio Biomedica de Bellvitge (IDIBELL), University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain 1
Key words: Candida; infection; liver transplantation; arteritis Correspondence to: Marta Bodro, Infectious Diseases Department, Hospital Universitari de Bellvitge, IDIBELL Research Institute, 08907-L’Hospitalet de Llobregat, Barcelona, Spain Tel: +34 93 260 7625 Fax: +34 93 260 7637 E-mail: [email protected]
Received 17 September 2013, revised 18 November 2013, accepted for publication 18 December 2013 DOI: 10.1111/tid.12218 Transpl Infect Dis 2014: 16: 465–468
Candida arteritis is an uncommon complication in solid organ transplant recipients. The few cases reported to date have been renal transplant patients (1–6). This entity is caused by either hematogenous or local spread of the yeast to the arterial wall leading to an intense inflammatory response and, as a consequence, the formation of an aneurysm and destruction of vascular structures. The source of fungal infection is difficult to ascertain because Candida species are normal commensals of the gastrointestinal tract in humans. The source may be donor-to-host transmission or contamination during organ procurement (1, 2). Here, we report the first case of Candida arteritis, to our knowledge, after liver transplantation.
Case report A 63-year-old man with hepatocellular carcinoma underwent surgical liver resection, but because of acute postoperative hepatic failure, an emergency liver transplantation was performed after 24 h of the initial surgery. The donor was an 86-year-old man who died from a vascular stroke and had been hospitalized for 1 day in the intensive care unit, but had not received antibiotic therapy. Blood cultures before procurement were negative. A choledocho-choledochostomy was performed and an arterial anastomosis was made as usual, between the patch from celiac trunk of the donor and the proper
465
Llado et al: Candida arteritis in a liver recipient
hepatic artery of the recipient. The cold ischemia time was 4 h. The immunosuppressive treatment included basiliximab, corticosteroids, and delayed initiation of mycophenolate mofetil and tacrolimus. The recipient received antibiotic prophylaxis with aztreonam and teicoplanin for 24 h. No fungal prophylaxis was administered. He had no history of invasive candidiasis and was not colonized with yeast before transplantation. Five days after transplantation, the preservation media showed Enterobacter cloacae and Enterococcus faecium, but the patient did not receive any antibiotic treatment, because there was no suspicion of infection. No fungus grew in the preservation fluid. The patient then developed a respiratory infection, and piperacillin-tazobactam was prescribed for 8 days. Abdominal ultrasound at 24 h and at 7 days after surgery, performed per protocol at our institution, was normal. He was transferred to the hospital ward after 6 days in the intensive care unit. On postoperative day 14, the patient complained of diffuse abdominal pain. The computed tomography scan showed a pseudoaneurysm in the proper hepatic artery with active bleeding, necessitating immediate operation (Fig. 1). An arterial rupture was found and resection of the affected artery and reconstruction with an arterial graft were performed. Broad-spectrum antibiotics and fluconazole therapy were initiated. Histologic examination of the hepatic artery showed necrohemorrhagic arteritis with abundant yeasts and pseudohyphae in the arterial wall (Fig. 2), subsequently identified as Candida albicans, Candida glabrata, and Candida tropicalis. Blood cultures were negative. Antifungal therapy with intravenous anidulafungin was prescribed for 6 weeks after surgery and then replaced by voriconazole for 4 additional months according to minimum inhibitory concentrations of the Candida species isolated in the arterial tissue (Table 1). Voriconazole serum levels were regularly determined and were within the therapeutic range. Five months after transplantation, the patient was admitted to the hospital for fever and delayed hepatic function. Voriconazole was replaced by anidulafungin because of the suspicion of hepatotoxicity and a computed tomography scan showed dilation of the bile duct. A percutaneous transhepatic cholangiography was performed, and the bile duct obstruction was resolved. However, liver function did not improve. The liver biopsy was unspecific. The patient’s liver function was progressively impaired, and he eventually died 8 months after transplantation. The autopsy analysis of the graft, including cultures and thorough histologic examination of the arterial hepatic graft anastomosis, ruled out fungal infection.
466
Fig. 1. Computed tomography scan showed a pseudoaneurysm (black arrow) in the proper hepatic artery with active bleeding, necessitating immediate operation.
Recipients from the same donor did not develop any complication after transplantation.
Discussion We describe the first case of Candida arteritis in a liver transplant recipient properly cured after surgical management and prolonged antifungal treatment. Candida arteritis usually occurs early after transplantation (1). The source of fungal infection is difficult to ascertain. Donor-to-host transmission has been suggested, although some authors have hypothesized that contamination during graft harvesting and processing is more likely. Albano et al. (2) identified episodes in which there was a close relationship between isolates from preservation fluids and isolates from the operative sites of recipients, so contamination during organ recovery from the donor was assumed. Moreover, among factors that might explain the contamination of the deceased organ donors, digestive tract rupture has been suggested (1, 2). Although transmission of pathogens by donors is a potential cause of infection in transplant recipients, routine microbiologic analysis of the preservation fluid is not well established. Only a few retrospective studies have analyzed the percentage of pathogen transmission from the preservation fluid and it ranges from 0% to 9.8% (7–13). In addition, the post-transplant antibiotic protocol was highly variable, including antifungal therapy in some cases (7–11). In some reports, Candida
Transplant Infectious Disease 2014: 16: 465–468
Llado et al: Candida arteritis in a liver recipient
A
B
Fig. 2. (A) Cross-section panoramic view of the artery with signs of acute arteritis with focal rupture of the arterial wall (arrow). (B) A closer examination highlights transmural necrosis and acute inflammatory infiltrate (hematoxylin–eosin, 49). Inset: Grocott stains identified abundant yeast and pseudohyphae morphologically consistent with Candida species.
Minimum inhibitory concentration (mg/L) of the Candida species isolated in the arterial tissue of the patient
Antifungal agent
Candida albicans
Candida tropicalis
Amphotericin B
0.5
0.5
0.5
Fluconazole
8
0.5
4
Posaconazole
0
0
0
0
Candida glabrata
Voriconazole
0
Anidulafungin
0
Micafungin
0
0
0
Caspofungin
0
0
0
Flucytosine
0.12
0.012
