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Scopulariopsis species are rarely but increasingly recognized as opportunistic pathogens in immunocompromised patients. We report on a patient suffering from cystic fibrosis who developed disseminated fungal infection due to a rare Scopulariopsis species, Microascus cirrosus, after heart and lung transplantation. Despite antifungal combination therapy with voriconazole and caspofungin, the patient died 4 weeks after transplantation. Diagnostic difficulties and optimal management of disseminated Scopulariopsis/Microascus infections are discussed. CASE REPORTA 36-year-old man suffering from cystic fibrosis was admitted to our hospital in June 2009 for a heart and bilateral lung transplantation. He had a first lung transplantation in 1997 but had chronic rejection since 2001 in spite of several immunosuppressive regimens. His medical history also included renal failure (hemodialysis since 2007), diabetes mellitus, and airway colonization with a multiresistant Pseudomonas aeruginosa. Short antifungal therapy courses had been prescribed over the past years for various yeasts (Candida spp.) and molds (Aspergillus, Paecilomyces, and Fusarium species) colonizing his respiratory tract, but there was no evidence of previous isolation of a Scopulariopsis species. At the time of admission, sputum cultures grew only Candida albicans, and fluconazole was thus prescribed (200 mg intravenously [i.v.] after each dialysis).Following graft surgery, the immunosuppressive regimen included induction therapy with basiliximab (anti-CD25 antibody [20 mg i.v. on the day of transplantation and on day 4]) and solumedrol (10 mg/kg of body weight on the day of transplantation, followed by three 120-mg doses per day), followed by cyclosporine adjusted according to dialysis parameters to reach therapeutic blood levels (300 to 350 ng/ml) and solumedrol. Antimicrobial therapy consisted of a broad-spectrum antibiotherapy with tobramycin, vancomycin, piperacillin, and tazobactam. Although the patient seemed to do well in the early postoperative period, with apyrexia and extubation on day 3, his white blood cell count (WBC) increased slowly starting on the day after transplantation, reaching 20 ϫ 10 9 cells/liter by day 8 postsurgery. On day 11 after the operation (WBC ϭ 30 ϫ 10 9 cells/liter), a thoracic computed tomodensitometry (TDM) revealed bilateral pulmonary effusions (Fig. 1A), which were drained on day 19 without clinical improvement. Bilateral hemorrhagic pleural fluid specimens revealed several regular, hyaline, and branched septate hyphae on direct examination ( Fig. 2A), leading to the diagnosis of proven invasive fungal infection (IFI) according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria (8). The patient was given an antifungal combination therapy of voriconazole i.v. (6 mg/kg every 12 h as a loading dose followed by two 4-mg/kg doses a day) and caspofungin (70 mg/day ...

BackgroundHomeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling.ObjectiveThis study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation.MethodsMicrobiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture.ResultsWe identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition.ConclusionsHost-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

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