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R.D. Boyce, P.J. Deziel, C.C. Otley, M.P. Wilhelm, A.J. Eid, N.L. Wengenack, R.R. Razonable. Phaeohyphomycosis due to Alternaria species in transplant recipients. Transpl Infect Dis 2010: 12: 242–250. All rights reserved Abstract: Alternaria species are members of a heterogenous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20-year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non-tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.

Arthurs SK, Eid AJ, Deziel PJ, Marshall WF, Cassivi SD, Walker RC, Razonable RR. The impact of invasive fungal diseases on survival after lung transplantation. Clin Transplant 2010: 24: 341–348. © 2009 John Wiley & Sons A/S. Abstract: Background: Recipients of lung transplants are at high risk of infectious complications. We investigated the epidemiology of infections after lung transplantation and determined their impact on survival. Methods: We retrospectively reviewed the medical records of patients who underwent lung transplantation at Mayo Clinic (Rochester) during 1990–2005. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazard modeling. Results: Sixty-nine lung transplants were performed during the 16-yr study period. The mean (±SD) patient age was 50.5 ± 9.7 yr; 45% were male. During the mean (±SD) follow-up period of 1188 (±1288) d, the cumulative percentage of patients with infections were: bacteria (52%), cytomegalovirus (CMV) (49%), other viruses (32%), fungi (19%), mycobacteria (7%), and Pneumocystis jiroveci (1%). The median survival time after lung transplantation was 5.02 yr. Kaplan–Meier estimation of one-, three-, and five-yr survival was 80%, 61%, and 50%, respectively. Overall, 37 (54%) patients died due to graft rejection and failure (35%), invasive fungal diseases (16%), post-transplant lymphoproliferative disorder and other malignancies (14%), cardiovascular diseases (5%), CMV disease (3%), bacterial infection (3%), or other causes (24%). Survival analysis using Kaplan–Meier estimation showed that invasive fungal disease (Aspergillus sp., n = 9, Candida sp., n = 2, Alternaria sp., n = 1, Rhizopus sp., n = 1, and/or Mucor sp., n = 1) was significantly associated with mortality (p = 0.0104). After adjusting for age and graft rejection, invasive fungal disease remains a significant predictor of mortality (p = 0.0262). Conclusion: Invasive fungal disease is significantly associated with all-cause mortality after lung transplantation. An aggressive antifungal preventive strategy may lead to improved survival after lung transplantation.

Infections due to Mycobacterium marinum are rarely encountered following organ and tissue transplantation. Herein, we report a case of M. marinum infection in a kidney and pancreas transplant recipient who manifested clinically with multiple locally spreading sporotrichoid-like cutaneous nodules in his left forearm. In order to provide a general overview of post-transplant M. marinum infections, we reviewed and summarized all previously reported cases of this infection that occurred after transplantation. Including our index case, all 6 cases presented with multiple cutaneous and subcutaneous nodules that had spread locally in the involved extremity. One patient had lesions located in non-contiguous body sites suggesting either systemic dissemination or multiple sites of inoculation. In all but 1 patient, the cutaneous nodules appeared in an ascending pattern and following exposure to fish tanks or after contact with the marine environment. The diagnosis of M. marinum infection was suspected on clinical grounds and confirmed by mycobacterial culture. Treatment consisted of at least 2 active antibiotics (such as rifamycins, ethambutol, tetracyclines, or macrolides) for 4-9 months, resulting in clinical cure or improvement. Relapse was observed in 1 patient despite completing 6 months of antibiotic therapy. One patient had surgical excision of the lesions. In conclusion, M. marinum should be considered as the cause of cutaneous and subcutaneous nodules in transplant recipients, particularly in the context of fish tank or marine exposure. Compared with the immunocompetent hosts, M. marinum infection may have a more aggressive clinical course after transplantation, and may require a longer duration of antibiotic treatment. Early diagnosis and treatment may prevent local spread and potential systemic dissemination.

Background: Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis. Methods: The medical records of all CMV D+/R− kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed. Results: During a four-yr-study period, a total of 225 CMV D+/R− transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV. Conclusions: Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R− solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.