Successful use of posaconazole to treat invasive cutaneous fungal infection in a liver transplant patient on sirolimus

Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.     

Invasive filamentous fungal infections associated with renal transplant tourism

S. Shoham, F. Hinestrosa, J. Moore Jr, S. O'Donnell, M. Ruiz, J. Light. Invasive filamentous fungal infections associated with renal transplant tourism.
Transpl Infect Dis 2010: 12: 371–374. All rights reserved Abstract: ‘Transplant tourism,’ the practice of traveling abroad to acquire an organ, has emerged as an issue in kidney transplantation. We treated a patient who developed invasive aspergillosis of the allograft vascular anastomosis after receiving a kidney transplant in Pakistan, prompting us to review the literature of invasive mycoses among commercial organ transplant recipients. We reviewed all published cases of infections in solid organ transplant recipients who bought their organs abroad and analyzed these reports for invasive fungal infections. Including the new case reported here, 19 cases of invasive fungal infections post commercial kidney transplant occurring in 17 patients were analyzed. Infecting organisms were Aspergillus species (12/19; 63%), Zygomycetes (5/19; 26%), and other fungi (2/19; 5%). Invasive mold infections were present at the transplanted graft in 6/17 patients (35%) with graft loss or death in 13/17 (76%) of patients and overall mortality (10/17) 59%. Invasive fungal infections, frequently originating at the graft site, have emerged as a devastating complication of commercial renal transplant and are associated with high rates of graft loss and death.     

High clinical suspicion of donor‐derived disease leads to timely recognition and early intervention to treat solid organ transplant‐transmitted lymphocytic choriomeningitis virus

Despite careful donor screening, unexpected donor‐derived infections continue to occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus (LCMV) is one such transplant‐transmitted infection that in previous reports has resulted in a high mortality among the affected OTRs. We report a LCMV case cluster that occurred 3 weeks post‐transplant in three OTRs who received allografts from a common organ donor in March 2013. Following confirmation of LCMV infection at Centers for Disease Control and Prevention, immunosuppression was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were initiated in OTRs. The liver recipient died, but right kidney recipients survived without significant sequelae and left kidney recipient survived acute LCMV infection with residual mental status deficit. Our series highlights how early recognition led to prompt therapeutic intervention, which may have contributed to more favorable outcome in the kidney transplant recipients.     

Everolimus associated interstitial pneumonitis: 3 Case reports

Like sirolimus, everolimus is an inhibitor of mTOR (mammalian target of rapamycin), used as an immunosuppressant in solid organ transplantation and as an antineoplastic agent. Its usage increases. Many cases of sirolimus-induced hypersensitivity pneumonitis were reported. To our knowledge only four cases of everolimus-associated interstitial pneumonitis have been reported in transplant recipients, three in heart and the other in kidney transplantation, with a favourable outcome after discontinuation. We report herein three cases of hypersensitivity pneumonitis due to everolimus.     

Clinical outcomes of solid organ transplant recipients with ehrlichiosis

Abstract: Because of our experience with severe Ehrlichia infections in lung transplant recipients, we reviewed all cases of ehrlichiosis in solid organ transplant recipients at Barnes-Jewish Hospital in St. Louis, Missouri. Between 1996 and 2007, 25 cases of ehrlichiosis were identified. We retrospectively collected demographic, clinical, laboratory, and outcomes data, and we compared the 5 cases in lung transplant recipients with 20 cases in other solid organ transplant recipients (heart, 2; kidney, 13; liver, 5). The presenting symptoms in the majority of both groups consisted of fever and headache. Clinical outcomes were worse in the lung transplant group and included a greater need for intensive care unit treatment (80% vs. 20%, P =0.02), longer length of hospital stay (21 vs. 5 days, P =0.02), and propensity to develop acute lung injury or acute respiratory distress syndrome (60% vs. 10%, P =0.04). No mortalities occurred in either group of patients. In an endemic area, ehrlichiosis is not unusual in solid organ transplant recipients, and lung transplant recipients tend to have a more severe illness.     

Dermatologic manifestations of infections in immunocompromised patients

Thirty-one immunocompromised patients (22 renal allograft recipients, 5 patients receiving chronic corticosteroid therapy, and 4 patients undergoing chemotherapy for acute leukemia) with significant dermatologic infection, excluding typical cellulitis and herpesvirus infections, were retrospectively identified over a 12-year period. Of these 31 patients, 15 (48%) had infection restricted to their skin, 6 (19%) appeared to have primary cutaneous infection that spread hematogenously to other parts of the body, 2 (6%) had infections of adjoining nasal tissue that spread to contiguous skin, and 8 (26%) appeared to have disseminated systemic infection that spread to the skin. In six of the eight patients with apparent secondary skin involvement, the development of the cutaneous lesion was the first clinical indication of disseminated infection. Eleven immunocompromised patients (35%) with bacterial infection of the skin or subcutaneous tissue were identified. These patients could be divided into three categories: leukemic patients with bacteremic gram-negative infection metastasizing to the skin (3 cases), renal transplant recipients with recurrent staphylococcal infection on and around the elbow ("transplant elbow") or streptococcal sepsis from a site of cellulitis (5 cases), and immunocompromised patients with opportunistic bacterial infection due to Nocardia asteroides or atypical mycobacteria (3 cases). Seventeen immunocompromised patients (55%) with fungal infection of the skin or subcutaneous tissue were identified. These included 12 patients with opportunistic fungal infection (Cryptococcus neoformans, 4 cases; Aspergillus species, 3 cases; Paecilomyces, 2 cases; Rhizopus species, 2 cases; and Candida tropicalis, 1 case) and 5 patients with extensive, confluent cutaneous dermatophyte infections. One patient with protothecosis and two patients with extensive papillomavirus infection were identified. Of these latter two cases, one had his immunosuppression discontinued, with clearing of his extensive warts; the other had confluent warts of the face and neck that subsequently underwent malignant degeneration to squamous cell carcinoma while chronic immunosuppressive therapy was continued.(ABSTRACT TRUNCATED AT 400 WORDS)     

Successful treatment with isavuconazole of subcutaneous phaeohyphomycosis in a kidney transplant recipient

Phaeohyphomycosis is a diverse group of uncommon mycotic infections caused by dematiaceous fungi which appears to be increasing in incidence, particularly in transplant recipients. Alternaria is the most frequent isolated genus. Subcutaneous, pulmonary and disseminated disease are the most common sites of Alternaria infection in solid organ transplant recipients. We report the first case, to our knowledge, of a kidney transplant recipient with Alternaria alternata subcutaneous infection who was successfully treated with isavuconazole.     

Immunosuppressive therapy and infection after kidney transplantation

J. Fortun, P. Martin‐Davila, J. Pascual, C. Cervera, A. Moreno, J. Gavalda, J.M. Aguado, P. Pereira, M. Gurguí, J. Carratala, M. Fogueda, M. Montejo, F. Blasco, G. Bou, J. Torre‐Cisneros; RESITRA Transplant Network. Immunosuppressive therapy and infection after kidney transplantation.
Transpl Infect Dis 2010: 12: 397–405. All rights reserved Abstract: Background. The role of immunosuppressive drugs in the development of infection in transplant recipients has been poorly analyzed. Objective. To evaluate the possible association between infection and immunosuppression regimens in a large cohort of renal transplant recipients. Methods. All renal transplant recipients included in the RESITRA prospective cohort from August 2003 to February 2005 with a minimum follow‐up of 3 months were studied. An intention‐to‐treat analysis was performed and patients were analyzed in groups according to the type of induction and initial maintenance therapy. Viral, bacterial, and fungal infections occurring during this period were evaluated. Results. A total of 1398 renal transplant recipients were studied. A maintenance regimen containing sirolimus was independently associated with a lower risk of cytomegalovirus (CMV) infection (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05–0.54) and with a higher rate of surgical site infection (OR, 3.21; 95% CI, 1.26–8.21). Excluding treatment used for acute rejection episodes, no other factors related to the immunosuppression regimens were associated with the development of bacteremia, urinary infections, pneumonia, or other infections. Conclusion. The use of sirolimus as maintenance therapy in kidney recipients is associated with a low rate of CMV infection and with a higher risk of surgical site infection.     

Primary cutaneous fungal infection after solid-organ transplantation: report of five cases and review.

Solid-organ transplant recipients who are receiving immunosuppressive therapy are at increased risk of acquiring opportunistic infections, particularly fungal infections. We present the cases of five liver transplant recipients who developed primary cutaneous opportunistic fungal infections that remained localized to the skin. These cases are compared with 27 previously reported cases of primary cutaneous fungal infections. In these previously reported cases, administration of systemic antifungal medications, including amphotericin B, ketoconazole, griseofulvin, and miconazole, resulted in a 71% survival rate. Medical and surgical therapy together resulted in an 86% survival rate, and surgical excision resulted in a 100% survival rate. Thus, regardless of the age of the patient, type of immunosuppressive therapy, clinical presentation, or organisms involved, surgical excision yielded the highest cure rate. When possible, surgical excision should be performed on solid-organ transplant recipients who acquire opportunistic fungal infections.     

Bacterial and mycobacterial pneumonia in transplant recipients

Bacteria and myobacteria are important pulmonary pathogens in transplant recipients and are the focus of this article. Although considerable overlap exists, there are significant differences in the epidemiology and clinical presentation of these organisms in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. The first section of this article focuses on infections in SOT recipients (predominantly heart, liver, lung, and kidney transplant recipients), and the latter addresses these infections in HSCT recipients.     

Pseudomonas aeruginosa endocarditis in renal transplant recipients

Infective endocarditis (IE) is a serious and life-threatening disease. Transplant recipients are at increased risk of acquiring serious infections. The most common organisms causing IE in solid organ transplant recipients are reported to be gram positive. IE due to Gram-negative organism has rarely been reported. We report 2 cases of renal transplant recipients who met the Duke's criteria for IE due to Pseudomonas aeruginosa.     

Intrarenal abscess caused by community‐associated methicillin‐resistant Staphylococcus aureus in a transplanted kidney

Emergence of multidrug‐resistant bacteria is important in solid organ transplant recipients, because it can jeopardize patient and graft survival. Methicillin‐resistant Staphylococcus aureus (MRSA) infections are not rare in kidney transplant recipients. On the other hand, infections related to community‐associated MRSA (CA‐MRSA) strains are seldom reported in the literature. Herein, we report the first patient, to our knowledge, with CA‐MRSA renal graft abscess who was successfully treated with drainage and parenteral antibiotics.     

An unusual etiology of viral hepatitis in three renal transplant recipients with normal graft function

Liver impairment in renal transplant recipients is not a common complication and is associated, in most cases, with viral infections (HBV, HCV, HVD, HGV) or drug hepatotoxicity (Cyclosporin, Azathioprine, statins). Cytomegalovirus (CMV) infection is common, with 50 to 80% of the adult population being seropositive for CMV antibodies. In immunocompetent individuals, primary infection is usually asymptomatic or associated with minor illness. CMV remains latent after primary infection. In immunocompromised patients, as in renal transplant recipients or transplant recipients of other solid organ or bone marrow, the virus can cause serious disease. This could be the result of newly acquired infection or reactivation of the latent virus. One of the organs involved in CMV disease is the liver. The subjects of this report are renal transplant recipients with liver impairment due to CMV induced acute hepatitis.     

Spontaneous clearance of hepatitis C after liver and renal transplantation

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.     

Respiratory Viral Infections in Pediatric Solid Organ and Hematopoietic Stem Cell Transplantation

Respiratory viruses are common in children, including pediatric recipients of both solid organ transplantation and hematopoietic stem cell transplantation. The prevalence and risk factors in each of these groups are reviewed. Furthermore, associated morbidity and mortality in pediatric transplant recipients with respiratory viral infections are addressed. The literature on specific prevention and treatment options for respiratory syncytial virus, adenovirus, influenza, and other respiratory viruses in pediatric solid organ and hematopoietic stem cell transplant recipients is reported.     

Sirolimus-associated interstitial pneumonitis in a renal transplant patient

INTRODUCTION: Sirolimus is a new immunosuppressive drug used in organ transplantation, particularly in renal transplantation. In the future, it could replace calcineurin inhibitors such as cyclosporine. It is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. Several interstitial pneumonitis associated with sirolimus has been previously described in renal transplant recipients associated with marked general symptoms. EXEGESIS: We report on a 65-year-old renal recipient presenting with a non typical case of sirolimus interstitial pneumonitis. He presented with fever and marked general symptoms for several months. CT scan showed a unilateral interstitial pneumonitis. After infectious, inflammatory and tumoral diseases were ruled out, sirolimus associated interstitial pneumonitis was evoked. The patient improved quickly after discontinuation of sirolimus. CONCLUSION: It is important to evoke, after eliminating other aetiologies, sirolimus induced pneumonitis in face of an organ transplant recipient presenting with marked general symptoms even if the pulmonary symptoms are not predominant.     

Prosthetic joint infection with Mycobacterium avium complex in a solid organ transplant recipient

Abstract: Prosthetic joint infection (PJI) occurs with significant morbidity and health care expenditure. Transplant recipients on immunosuppressive medications are at increased risk for infections caused by less common organisms at unusual sites. Here we report a case of isolated PJI with Mycobacterium avium complex (MAC) in an immunosuppressed failed kidney transplant recipient and review the literature on this unique infection. We discuss the likely pathogenesis of PJI with MAC including the role of biofilm formation by non‐tuberculous mycobacteria. The possible role of cytokine milieu alteration by immunosuppressive therapy, particularly the reduction in interferon‐gamma levels, as a predisposing factor for non‐tuberculous mycobacterial infections in transplant recipients is explored. Lastly, we review the role of immune cell function assay in predicting the susceptibility to infection in our patient specifically and in solid organ transplant recipients in general.     

Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients

D. Neofytos, J.A. Fishman, D. Horn, E. Anaissie, C.‐H. Chang, A. Olyaei, M. Pfaller, W.J. Steinbach, K.M. Webster, K.A. Marr. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.
Transpl Infect Dis 2010: 12: 220–229. All rights reserved Abstract: Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received ≥2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12‐week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non‐lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.     

Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients

Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.     

Prophylaxis against pulmonary viral and fungal infections in solid organ transplant recipients

Pulmonary viral and fungal infections in solid organ transplant recipients are one of the most common and potentially life-threatening infections. Understanding the strategies used for prophylaxis and prevention of these infections is critical for the health and well-being of transplant recipients. Prophylactic measures range from simple patient education to complex chemoprophylactic interventions; however, a multifaceted approach is most often required. This article focuses on strategies to prevent pulmonary viral and fungal infections in transplant recipients, with an emphasis on recent evidence that may influence practice guidelines.