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Scedosporiosis in a Combined Kidney and Liver Transplant Recipient: A Case Report of Possible Transmission from a Near-Drowning Donor.

1. Introduction

Scedosporium is a saprobic fungus that naturally occurs in soil, manure, sewage, and water bodies polluted by environmental contaminants. Cases of infections with Scedosporium spp. are reported worldwide and can range in severity from colonization or local infection to disseminated disease [1-5]. S. apiospermum most commonly infects the lungs as inhalation is often the suspected mode of organism acquisition [6].

The genus Scedosporium includes, but is not limited to, three species that cause life-threatening infections in humans: Scedosporium apiospermum, Scedosporium prolificans (recently renamed Lomentospora prolificans), and Scedosporium aurantiacum [7]. Scedosporium spp. appear as branching septate hyphae when isolated on standard culture media.

Scedosporium spp. have been implicated in neardrowning accidents [8-10]. Indeed Scedosporium spp. are the most common cause of fungal pneumonia, infection of the central nervous system, and disseminated disease following near-drowning events. There are few cases of donor to recipient transmission of infection of Scedosporium spp. and even fewer reports of near-drowning donor transmission of diseases [11, 12]. We report the clinical course and management of disseminated S. apiospermum infection in a combined kidney and liver transplantation case receiving organs from a brain-dead donor who suffered a neardrowning accident; we further review the literature on scedosporiosis in solid organ transplant recipients.

2. Case Presentation: Donor

A 41-year-old male fell into a freshwater lake. Emergency responders pulled him from the lake and return of spontaneous circulation was achieved after twenty minutes of resuscitation. Subsequent chest radiographs showed development and worsening of bilateral opacities suspicious for pneumonia. Brain death was declared three days after hospital admission.

3. Case Presentation: Recipient

A 66-year-old male actively listed for a kidney and liver transplant presented to the surgical intensive care unit with sepsis and an oxacillin-sensitive Staphylococcus aureus bacteremia. He was treated with appropriate antibiotic therapy. He then developed acute tubular necrosis requiring continuous venovenous hemofiltration (CVVH). The patient had a chest X-ray showing mild pulmonary congestion and bronchoscopy was not performed as the patient did not show signs of pneumonia. After two weeks within his admission, the patient was treated for Escherichia coli bacteremia with piperacillintazobactam. Repeat blood cultures were negative after two days of therapy.

While the patient was hospitalized, a donor became available. The donor kidney and liver were grossly normal. The patient underwent a combined kidney and liver transplant for chronic kidney failure with associated liver cirrhosis caused by the hepatitis C virus and alcoholism. The explanted liver was cirrhotic without any malignancy. At the time of transplantation, the patient's Model for End Stage Liver Disease (MELD) score was 40, having been decompensated in the surgical intensive care unit for the previous month. A summary of the patient's immunosuppression and antifungal management after transplant is provided in Figure 1.

The patient was given methylprednisolone 500 mg and mycophenolate mofetil 1,000 mg intraoperatively as induction immunosuppression. Maintenance immunosuppression protocols were followed after transplant. CVVH was performed intraoperatively and was discontinued on postoperative day (POD) 1 when renal graft function improved. The patient's hospital stay was complicated by a contained urine leak from the ureteroureterostomy which was managed nonoperatively with drains and ureteral stents. On POD 8, the patient was transferred out of the intensive care unit and on POD 14, to the inpatient rehab care unit as graft function continued to improve. The hepatic transaminases fluctuated and, on POD 25, he was transferred back to the surgical intensive care unit with peritonitis. As infection was suspected, immunosuppression was restricted to the use of corticosteroids tapered down to prednisone 5 mg daily. The patient was taken backto the operating room on POD 28 for a peritoneal washout. Cultures obtained during the procedure are presented in Tables 1 and 2. Of most concern was the S. apiospermum isolated from the perihepatic, perinephric, and biloma fluid. Endoscopic Retrograde Cholangiopancreatography (ERCP) was performed the following day, which did not reveal any extravasation. Discovery of S. apiospermum prompted contact with the Centers for Disease Control and Prevention (CDC), the Disease Transmission Advisory Committee (DTAC) of the United Network for Organ Sharing (UNOS), and the transplant centers treating recipients of allografts from the same donor. Other recipients had no evidence of infection.

On POD 28, due to worsening hemodynamics and peritonitis, another laparotomy and another washout were performed to evacuate an infected hematoma. The entire peritoneal surface was lined with mold. On POD 32, a mold suggestive of Scedosporium spp. grew from surgical cultures. Expert opinion for the management of our patient's suspected S. apiospermum infection was to use voriconazole targeting a trough of 2-4 mcg/mL, which we started on POD 32. Additionally, terbinafine was started for suspected synergy with voriconazole. A sample of the S. apiospermum was sent out for synergy studies which were expected to take a week or more to be conclusive. On POD 41 S. apiospermum was identified. Laboratory results suggested terbinafine was not synergistic with voriconazole. Additionally, terbinafine is distributed rapidly to skin and bone and as such is not distributed well into visceral tissue and accumulation of terbinafine may cause hepatotoxicity. In response, terbinafine was discontinued and granulocyte macrophage colony-stimulating factor (GMCSF) initiated on POD 42. The patient developed neurologic deficits with decreased vision to the right side and blurred vision bilaterally on POD 46. Magnetic resonance imaging (MRI) of the brain, shown in Figure 2, revealed multiple ring-enhancing lesions in the supratentorial compartment consistent with hematogenous central nervous system (CNS) scedosporiosis. We continued treatment with antifungal therapy. He developed septic shock and expired on POD 55.

4. Discussion

Differential diagnoses for opportunistic pathogens causing pneumonia related to near-drowning events include several key pathogenic bacteria and fungi. Gram negative bacteria are most often the causative agents in near-drowning cases [13]. Aeromonas spp. have been described most often in near-drowning pneumonia cases. Aeromonas spp. naturally thrive in fresh and brackish waters and have been isolated in humans in wound and gastrointestinal infections after exposure to contaminated water. Other potential bacterial pathogens include Pseudomonas aeruginosa, Legionella spp., Klebsiella spp., and other Enterobacteriaceae [13]. Scedosporium spp. are the most common cause of invasive fungal infection, including pneumonia, CNS disease, and dissemination following near-drowning.

We identified 60 published cases of scedosporiosis after solid organ transplantation between the year 2000 and the present. Few were cases of scedosporiosis after solitary liver transplantation (5/60); most were reported following solitary lung (18/60) or kidney (18/60) transplantation. Table 3 [2, 12, 14-42] provides a summary of the comprehensive literature review performed. S. apiospermum was isolated in the majority of cases, though S. prolificans and S. aurantiacum were also isolated. In four cases, both S. apiospermum and S. prolificans were identified in the same patient. In patients who had infections with a single isolate of Scedosporium spp., the observed mortality rates of S. apiospermum, S. prolificans, and S. aurantiacum were 54.5% (24/44), 70% (7/10), and 100% (3/3), respectively (excluding four cases with combined infections). Observed mortality of all Scedosporium spp. infections was 59% (36/61) including our patient case.

Kim et al. reported three fatal and two nonfatal cases of scedosporiosis following solid organ transplantation from the same donor who was victim to a near-drowning accident [12]. Additionally, they reviewed national Korean data on transplants and found that, among 2600 deceased-donor transplants over thirteen years, 27 (1%) of donors were victims of drowning. We accessed data from the United States Organ Procurement and Transplantation Network and found a similar rate: in 2015,102/7586 (approximately 1.3%) of solid organ donors died of near-drowning events [43]. While this is a low percentage of all donors, the significance of our case is enhanced by the 58.3% mortality rate of infections involving Scedosporium spp. after solid organ transplantation.

At our center, liver transplant recipients are given antifungal prophylaxis based on their risk level. We stratify higher risk patients as those with MELD scores greater than 35, renal failure, requiring hemodialysis or CVVH prior to transplantation, recurrent spontaneous bacterial peritonitis, or preoperative prealbumin less than 10. High risk liver transplant recipients receive micafungin intravenously unless resistant Candida glabrata, Aspergillus spp., or Cryptococcus spp. are suspected; in such cases, amphotericin B lipid complex or voriconazole would be used. Our patient was classified as high risk and given micafungin prophylaxis.

All cases of suspected donor-derived infections should be reported to the DTAC. Communications with the CDC, DTAC, and the centers treating the recipients of the other organs provided by this donor revealed the recipient of the heart was receiving voriconazole prophylaxis, while the recipients of the other kidney and the pancreas were not. To the best of our knowledge, no other recipient of this donor's organs is infected with Scedosporium spp. The other centers were advised by the CDC to commence voriconazole prophylaxis for an undetermined duration. Expert opinion for the management of our patient's scedosporiosis was voriconazole targeting a trough of 2-4mcg/mL. Additionally, immunosuppression was to be limited or discontinued to improve infection clearance.

S. apiospermum is inherently resistant to amphotericin B, including the lipid formulations. Of the newer triazole antifungals, data on the in vitro activity of voriconazole is most robust, showing activity against S. apiospermum with MICs of 0.12 to 0.5 mcg/mL in clinical isolates [30]. Because of poor activity with single agents, various antifungal combinations have been examined for efficacy against S. apiospermum. Strong synergy was found in vitro between voriconazole and terbinafine against clinical isolates of Scedosporium spp. [30]. Combination of micafungin and voriconazole has demonstrated a synergistic effect against several fungi in vitro including Scedosporium spp. The synergistic mechanism may include reorganization of the cell wall allowing increased exposure of beta-glucan to the immune system [44].

In addition to antifungal agents, GM-CSF has been studied with some success [44,45]. While antifungal therapy remains crucial to recovery, the treatment of scedosporiosis infections depends on the function of the host's innate immune system, in particular, polymorphonuclear cells (PMNs). The mechanism of GM-CSF increases the antifungal action of PMNs in vitro [45].

Despite good allograft function, our patient did not survive disseminated infection with S. apiospermum after combined kidney and liver transplantation. The exact mode of transmission and acquisition of S. apiospermum in this patient remains uncertain. We suspect donor to recipient transmission as the donor was the victim of a near-drowning event and had chest radiographs suspicious for pneumonia; however, we cannot rule out recipient colonization or nosocomial infection after the transplant.

Infections caused by Scedosporium spp. following solid organ transplant, while not common, are often fatal for recipients. There are no standards of practice for prophylaxis for patients at risk for developing scedosporiosis, such as recipients of organs from nearly drowned donors. Considering our case and the scedosporiosis mortality rate over 50% and the low rate of nearly drowned donors, we recommend screening for Scedosporium spp. when donated organs originate from a near-drowning victim. 10.1155/2016/1879529

Competing Interests

The authors declare that there is no significant conflict of interests regarding the publication of this paper.


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Rachael Leek, (1) Erika Aldag, (1) IramNadeem, (1) Vikraman Gunabushanam, (1) Ajay Sahajpal, (1, 2) David J. Kramer, (2,3) and Thomas J. Walsh (4)

(1) Department of Abdominal Transplant, Aurora St. Luke's Medical Center, Milwaukee, WI, USA

(2) University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA

(3) Department of Critical Care, Aurora St. Luke's Medical Center, Milwaukee, WI, USA

(4) Weill Cornell Medicine, Cornell University and New York Presbyterian Hospital, New York, NY, USA

Correspondence should be addressed to Erika Aldag;

Received 29 August 2016; Accepted 6 November 2016

Academic Editor: Graeme Forrest

Caption: Figure 1: Antifungal agents and immunosuppression management.

Caption: Figure 2: MRI of the brain. Multiple ring-enhancing lesions with associated diffusion restriction and T2/FLAIR hyperintensity are present throughout the supratentorial white matter.
Table 1: Culture results.

Date         Culture site            Source             Result

                                                     C. tropicalis
POD 28     Abdominal fluid      Surgical specimen     E. faecalis
                                                        E. coli
                                                      M. morganii
                                                      E. faecium
POD 28       Biloma fluid       Surgical specimen     E. faecalis
                                                    S. apiospermum
                                                     C. tropicalis
                                                    S. apiospermum
POD 28    Perihepatic fluid     Surgical specimen     E. faecium
                                                     C. tropicalis
POD 28   Perinephric hematoma   Surgical specimen   S. apiospermum
POD 32      Abdominal clot      Surgical specimen   S. apiospermum
POD 32    Intestinal serosal    Surgical specimen   S. apiospermum
                                                      E. faecium
POD 50   LUQ abdominal fluid    Surgical specimen     C. glabrata
                                                     C. tropicalis
POD 50   Cerebrospinal fluid     Lumbar puncture       Negative

Table 2: Susceptibility testing of fungal isolates.

Isolate                   Resistant (MIC)       Intermediate (MIC)

Scedosporium          5-Fluorocytosine (>64),
apiospermum            amphotericin B (>16),
                         caspofungin (>8),             None
                         micafungin (>8),
                         terbinafine (>2)

Candida tropicalis             None                    None

Candida glabrata               None                    None

Isolate                            Susceptible (MIC)

                                    Voriconazole (1)

                      Caspofungin ([less than or equal to] 0.25),
Candida tropicalis      fluconazole ([less than or equal to] 1),
                      voriconazole ([less than or equal to] 0.12)
                                    Caspofungin (2),
Candida glabrata        fluconazole ([less than or equal to] 1),
                      voriconazole ([less than or equal to] 0.12)

Table 3: Review of solid organ transplant-associated Scedosporium

Ref #    Year    Recipient information     Recipient

                 Age (years)   Gender      organ(s)

[14]     2000        67         Male         Heart
                     42        Female     Heart/lung
                     22        Female     Heart/lung
[15]                 42         Male      Heart/lung
         2001        49         Male         Lung
                     39         Male         Lung
                     52        Female        Lung
                     38        Female     Heart/lung
                     58        Female        Liver
                     37         Male         Lung
                     30         Male         Lung
[16]     2002        37        Female     Heart/lung
                     39         Male         Liver
                     67         Male         Heart
                     36         Male        Kidney
[17]     2002        49         Male        Kidney
[18]     2002        62        Female       Kidney
                     58         Male        Kidney
[19]     2002        64        Female        Lung
[20]     2002        71         Male         Heart
[21]     2003        24         Male         Lung
                     59         Male        Kidney
[22]     2004        50         Male        Kidney
[23]     2004        58         Male        Kidney

[24]     2004        56        Female        Lung
                     55         Male      Small bowel
                     40         Male    Kidney/pancreas
                     67         Male        Kidney

                     51        Female     Small bowel

                     67         Male         Heart
                     17         Male         Liver
[25]     2005        64         Male         Liver
                     45         Male         Heart
                     56         Male         Liver
                     44        Female        Heart
                     68         Male        Kidney
                     52         Male      Small bowel

                     62         Male    Kidney/pancreas
[26]     2005        26        Female        Lung
[27]     2006        58         Male        Kidney
                     57         Male         Lung
[28]     2006        63         Male         Lung

[29]     2007        59        Female       Kidney
[30]     2007        43         Male         Lung

[31]     2008        70         Male        Kidney
[32]     2009        65        Female       Kidney
[33]     2010        37        Female        Lung

[34]     2011        16        Female        Lung
[35]     2012        35         Male      Lung/liver

[36]     2012        37        Female        Lung

[37]     2013        17        Female        Lung

[38]     2013        70        Female        Lung

[39]     2014        50        Female       Kidney

[40]     2014        35         Male        Kidney

[41]     2015        70         Male         Heart
                     19         Male         Heart
[12]     2015        56         Male        Kidney

                     57        Female       Kidney
[2]      2015        40         Male        Kidney
[42]     2015        18        Female        Lung

Ref #    Year     Species of Scedosporium

[14]     2000           apiospermum
                 prolificans + apiospermum
[15]             prolificans + apiospermum
         2001    prolificans + apiospermum
                 prolificans + apiospermum
[16]     2002           apiospermum
[17]     2002           apiospermum
[18]     2002           apiospermum
[19]     2002           apiospermum
[20]     2002           apiospermum
[21]     2003           apiospermum
[22]     2004           apiospermum
[23]     2004           apiospermum

[24]     2004           prolificans


[25]     2005           apiospermum

[26]     2005           apiospermum
[27]     2006           apiospermum
[28]     2006           apiospermum

[29]     2007           apiospermum
[30]     2007           apiospermum

[31]     2008           prolificans
[32]     2009           apiospermum
[33]     2010           apiospermum

[34]     2011           apiospermum
[35]     2012           apiospermum

[36]     2012           apiospermum

[37]     2013           apiospermum

[38]     2013           prolificans

[39]     2014           apiospermum

[40]     2014           prolificans

[41]     2015           apiospermum
[12]     2015           aurantiacum

[2]      2015           apiospermum
[42]     2015           apiospermum

Ref #    Year          Treatment approach         Outcome

[14]     2000             Voriconazole            Deceased
                   Fluconazole, itraconazole      Deceased
                   Fluconazole, itraconazole      Deceased
[15]               Fluconazole, itraconazole       Alive
         2001      Fluconazole, itraconazole      Deceased
                   Fluconazole, itraconazole       Alive
                   Fluconazole, itraconazole       Alive
                   Fluconazole, itraconazole      Deceased
                    Itraconazole, miconazole       Alive
                          Itraconazole            Deceased
                   Amphotericin B, miconazole     Deceased
[16]     2002              Miconazole             Deceased
                 5-Flucytosine, amphotericin B    Deceased
                   Itraconazole, voriconazole     Deceased
                    Itraconazole, miconazole      Deceased
[17]     2002             Voriconazole            Deceased
[18]     2002                 None                Deceased
                   Itraconazole, voriconazole      Alive
[19]     2002     Amphotericin B, itraconazole    Deceased
[20]     2002             Itraconazole             Alive
[21]     2003             Voriconazole             Alive
                          Voriconazole             Alive
[22]     2004             Voriconazole             Alive
[23]     2004     Amphotericin B, fluconazole,     Alive
                    itraconazole, miconazole
[24]     2004             Voriconazole            Deceased
                         Amphotericin B           Deceased
                          Voriconazole             Alive
                         Amphotericin B            Alive

                 Amphotericin B, Voriconazole,    Deceased
                          Voriconazole            Deceased
                          Voriconazole            Deceased
[25]     2005                 None                Deceased
                          Itraconazole            Deceased
                          Voriconazole            Deceased
                         Amphotericin B           Deceased
                          Voriconazole             Alive
                 Amphotericin B, Voriconazole,     Alive
                          Voriconazole             Alive
[26]     2005       Miconazole, voriconazole      Deceased
[27]     2006       Miconazole, voriconazole       Alive
                   Terbinafine, voriconazole       Alive
[28]     2006      Liposomal amphotericin B,       Alive
                   terbinafine, voriconazole

[29]     2007             Voriconazole             Alive
[30]     2007      Caspofungin, itraconazole,     Deceased
                    liposomal amphotericin B
[31]     2008      Terbinafine, voriconazole       Alive
[32]     2009             Voriconazole             Alive
[33]     2010      Caspofungin, terbinafine,      Deceased
[34]     2011             Voriconazole             Alive
[35]     2012      Caspofungin, voriconazole      Deceased
                  Aerosolized amphotericin B,
[36]     2012      caspofungin, itraconazole,     Deceased
[37]     2013      Caspofungin, posaconazole,      Alive
[38]     2013      Caspofungin, terbinafine,      Deceased
[39]     2014             Voriconazole             Alive
                    Itraconazole, liposomal
[40]     2014     amphotericin B, micafungin,     Deceased
[41]     2015      Posaconazole, terbinafine      Deceased
                   Amphotericin B prophylaxis     Deceased
[12]     2015       Itraconazole, liposomal       Deceased
                         amphotericin B
                   Caspofungin, voriconazole      Deceased
[2]      2015             Voriconazole            Deceased
[42]     2015      Terbinafine, voriconazole       Alive
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Title Annotation:Case Report
Author:Leek, Rachael; Aldag, Erika; Nadeem, Iram; Gunabushanam, Vikraman; Sahajpal, Ajay; Kramer, David J.;
Publication:Case Reports in Transplantation
Article Type:Case study
Date:Jan 1, 2016
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