Aspergillus tubingensis Endocarditis: A Case Report and Review of the Literature

Abstract

Aspergillus endocarditis is a rare infection that may affect immunocompetent patients following heart valve replacement or heart surgery. We report the case of a 39 year old woman with a history of intravenous drug use who developed endocarditis with direct examination of the resected valve and vegetation showing the presence of mycelia. Cultures were positive for an Aspergillus of section Nigri, which was subsequently identified as Aspergillus tubingensis by sequencing. The clinical course was favorable following surgery and prolonged antifungal therapy (8 months in total). Antifungal susceptibility testing showed good in vitro activity of amphotericin B, voriconazole and echinocandins against planktonic cells of this A. tubingensis isolate. However, only amphotericin B displayed significant activity against biofilms. In vitro combinations of voriconazole or amphotericin B with echinocandins did not meet the criteria of synergism. Our review of the literature identified 17 other cases of endocarditis attributed to Aspergillus of section Nigri with an overall mortality rate of 57% (100% in the absence of surgery). Endocarditis caused by Aspergillus niger and related cryptic species are rare events, for which surgical management appears to be crucial for outcome. While amphotericin B was the only antifungal drug displaying significant anti-biofilm activity, the type and duration of antifungal therapy remain to be determined.

Keywords: Aortitis; Aspergillus niger; Fungal biofilm; Invasive aspergillosis; Section Nigri.

Fig. 1

Case report: radiological and microbiological images. Panel A Image of the transoesophageal cardiac echography showing a motile element of 11 mm (yellow arrow) on the right coronary leaflet of the biological prosthetic aortic valve. Panel B Image of the direct examination of the valvular tissue after silver staining showing mycelial elements with septate and 45° branching hyphae consistent with an Aspergillus spp

Fig. 2

Anti-biofilm activity of antifungal drugs against Aspergillus tubingensis. The anti-biofilm activity of antifungal drugs was measured against the sessile forms of the A. tubingensis isolate of the present case using the XTT reduction assay. Absorbance (λ_485nm) was measured after 16 h of drug exposure and expressed as relative optical density (OD). A Amphotericin B (AmB) alone and combined with caspofungin (CAS, fixed dose of 0.25 µg/ml), B voriconazole (VRC) alone and combined with caspofungin (CAS, fixed dose of 0.25 µg/ml), C caspofungin, D isavuconazole. The sessile minimal inhibitory concentration (SMIC), defined as the concentration of the drug achieving a 50% decrease of relative OD, was 1 µg/ml, > 4 µg/ml, > 1 µg/ml, and > 8 µg/ml for amphotericin B, voriconazole, caspofungin and isavuconazole, respectively. The addition of caspofungin to amphotericin B or voriconazole did not result in any additive effect