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      Mucormycosis in a Renal Transplant Recipient: Case Report and Comprehensive Review of Literature

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          Abstract

          Mucormycosis is a rare but devastating infection. We present a case of fatal disseminated mucormycosis infection in a renal transplant patient. Uncontrolled diabetes mellitus and immunosuppression are the major predisposing factors to infection with Mucorales. Mucorales are angioinvasive and can infect any organ system. Lungs are the predominant site of infection in solid organ transplant recipients. Prompt diagnosis is challenging and influences outcome. Treatment involves a combination of surgical and medical therapies. Amphotericin B remains the cornerstone in the medical management of mucormycosis, although other agents have been used. Newer agents are promising.

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          Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis.

          Dimitrios Kontoyiannis, Edwin Lewis, Georgios Chamilos (2008)
          Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome. Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.
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            Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis.

            Christopher D Pfeiffer, Jason P. Fine, Nasia Safdar (2006)
            A double-sandwich enzyme-linked immunosorbent galactomannan assay has been approved for surveillance for invasive aspergillosis in immunocompromised patients. We undertook a meta-analysis to assess the accuracy of a galactomannan assay for diagnosing invasive aspergillosis. Studies of the galactomannan assay that used the European Organization for Research and Treatment of Cancer or similar criteria as a reference standard and provided data to calculate sensitivity and specificity were included. Pooled sensitivity and specificity and summary measures of accuracy, Q* (the upper left-most point on the summary receiver-operating characteristic curve), mean D (a log odds ratio), and Youden index were calculated. Subgroup analyses were performed to explore heterogeneity. Twenty-seven studies from 1966 to 28 February 2005 were included. Overall, the galactomannan assay had a sensitivity of 0.71 (95% confidence interval [CI], 0.68-0.74) and specificity of 0.89 (95% CI, 0.88-0.90) for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were 0.54 (95% CI, 0.41-0.65), 2.74 (95% CI, 21.12-3.36), and 0.80 (95% CI, 0.74-0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that the performance of the test differed by patient population and type of reference standard used. Significant heterogeneity was present. The galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis in immunocompromised patients. The test is more useful in patients who have hematological malignancy or who have undergone hematopoietic cell transplantation than in solid-organ transplant recipients. Further studies with attention to the impact of antifungal therapy, rigorous assessment of false-positive test results, and assessment of the utility of the test under nonsurveillance conditions are needed.
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              Recent advances in the management of mucormycosis: from bench to bedside.

              Christopher Walsh, John Edwards, Leena Ibrahim … (2009)
              Recent therapeutic advances have the potential to improve outcomes of mucormycosis. Lipid formulations of amphotericin B (LFAB) have evolved as the cornerstone of primary therapy for mucormycosis. Posaconazole may be useful as salvage therapy, but it cannot be recommended as primary therapy for mucormycosis on the basis of available data. Preclinical and limited retrospective clinical data suggest that combination LFAB-echinocandin therapy may improve survival during mucormycosis. A definitive trial is needed to confirm these results. Combination therapy with LFAB and the iron chelator, deferasirox, also improved outcomes in animal models of mucormycosis. In contrast, combination polyene-posaconazole therapy was of no benefit in preclinical studies. Adjunctive therapy with recombinant cytokines, hyperbaric oxygen, and/or granulocyte transfusions can be considered for selected patients. Early initiation of therapy is critical to maximizing outcomes; recent developments in polymerase chain reaction technology are advancing early diagnostic strategies. Prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis.
              Article 0 comments Cited 133 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nephrol
                Journal ID (iso-abbrev): Int J Nephrol
                Journal ID (publisher-id): IJN
                Title: International Journal of Nephrology
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-214X
                ISSN (Electronic): 2090-2158
                Publication date (Print): 2014
                Publication date (Electronic): 12 February 2014
                Volume: 2014
                Electronic Location Identifier: 950643
                Affiliations
                1Division of Nephrology and Hypertension, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, CFP-514, Detroit, MI 48202, USA
                2Division of Infectious Diseases, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA
                Author notes

                Academic Editor: Tibor Nadasdy

                Article
                DOI: 10.1155/2014/950643
                PMC ID: 3944654
                SO-VID: 6f8eac6c-685a-45ac-8fe5-04de031e4121
                Copyright © Copyright © 2014 Tamim Hamdi et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 26 November 2013
                Date accepted : 27 December 2013
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Nephrology
                Data availability:
                ScienceOpen disciplines: Nephrology

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