Treatment of cirrhotic patients with spontaneous peritonitis using antibiotics occasionally fails. Fungal infections may be one of the causes of antibiotic treatment failure in such patients. In this study we evaluated the clinical significance and characteristics of spontaneous fungal peritonitis (SFP). Consecutive cirrhotic patients with spontaneous peritonitis treated between 2000 and 2005 at a tertiary care center in Seoul, Korea, were included. We analyzed the clinical characteristics and the prognosis of SFP patients compared with patients with spontaneous bacterial peritonitis (SBP). During the study period 416 patients developed spontaneous peritonitis and 15 (3.6 %) had SFP. Compared with patients with SBP, nosocomial peritonitis (peritonitis that developed after hospitalization for >72 h) was more common and the Child-Pugh score was higher in SFP patients (both, P < 0.01). Ten patients were infected with Candida spp. (C. albicans, 8; C. tropicalis, 1; C. glabrata, 1), and 5 with Cryptococcus neoformans. Eleven patients were co-infected with bacteria that were susceptible to the antibiotics administered. Only 5 patients were treated using appropriate anti-fungal agents. The 1-month mortality rate for SFP patients was 73.3 % (11 out of 15; median time to death, 2 days [range, 0-22]), which was significantly higher than patients with SBP alone (28.7 %, P = 0.0007). SFP is severe complication related to high mortality in cirrhotic patients. A longer admission and a higher Child-Pugh score may be risk factors. Immediate anti-fungal treatment is warranted in patients with spontaneous peritonitis, once fungus is found in the ascitic fluid.

The 6′-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell Sadenosyl-L-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6′position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N 6 -methyladenosine analogues 2a−e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a−c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6′,6′-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6′-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.

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