Fatal Invasive Infection with Fungemia Due to Microascus cirrosus after Heart and Lung Transplantation in a Patient with Cystic Fibrosis

Abstract

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 ...

Scopulariopsis, a Poorly Known Opportunistic Fungus: Spectrum of Species in Clinical Samples and In Vitro Responses to Antifungal Drugs

“…In agreement with earlier reviews of clinical cases (17,22), S. brevicaulis was the most commonly isolated species in our study. S. gracilis was the second most commonly isolated species in our study, which is interesting since this fungus has never been reported in human infections or isolated from clinical specimens.…”

“…However, a thorough taxonomic molecular study is still lacking. Scopulariopsis isolates from clinical cases were identified mostly by performing a BLAST search in GenBank (17,21,22). Our study demonstrated that this approach is not very useful, mainly due to the lack of reference sequences for comparison.…”

“…Histopathology has limited significance in diagnostics since in tissue, the fungi show features similar to those of other more common pathogenic molds, such as Aspergillus or Fusarium species (18,20). The sequencing of the ribosomal operon has been used for the identification of clinical strains of Scopulariopsis, although the results may not be reliable because of insufficient availability of reference sequences in the public databases (17,18,21,22). Interestingly, due to the high genetic variability of the internal transcribed spacer (ITS) sequences found in a large set of Scopulariopsis strains isolated from cheese, Ropars et al (23) used the combined analysis of partial sequences of the long subunit (LSU) rRNA gene, ␤-tubulin (TUB), and elongation factor 1-␣ (EF1-␣) genes for the taxonomic circumscription of Scopulariopsis species and proposed the EF1-␣ gene to be the most phylogenetically informative genomic region for identifying Scopulariopsis species.…”

“…The appropriate therapy for Scopulariopsis infections has yet to be defined (22,24). The effectiveness of AMB has been estimated to be only about 40% of successful treatments (24), which has resulted in high mortality rates and infection relapses (15,20).…”

“…In vitro antifungal susceptibility studies on these fungi are scarce and have involved mainly topical drugs. Several clinical reports have underlined the lack of correlation between in vitro susceptibility test results and clinical outcomes (21,22,25).…”