Evaluation of the feasibility of EUCAST RAST using antimicrobial disks available in Japan.

BACKGROUND: In November 2018, the European Committee for Antimicrobial Susceptibility Testing (EUCAST) established rapid antimicrobial susceptibility testing (RAST), which could be performed directly on positive blood culture samples. Although concentrations of antimicrobial agents in several antimicrobial disks available in Japan are different from those recommended by the EUCAST, the feasibility of EUCAST RAST using antimicrobial disks available in Japan remains to be evaluated. METHODS: Blood culture bottles spiked with 127 clinical isolates (65 Escherichia coli and 62 Klebsiella pneumoniae) were tested by RAST for cefotaxime (CTX), ceftazidime (CAZ), meropenem, and ciprofloxacin using antimicrobial disks available in Japan, and compared with a reference AST method using automated AST instrument (VITEK®2). RESULTS: The overall category agreement (CA) for RAST using antimicrobial disks available in Japan was 96.3%, 96.8%, and 95.6% after 4, 6, and 8 h of incubations, respectively. However, the CAZ RAST for E. coli showed major error of 8.2% (8 h incubation) for the Sensi disk, 14.3% (6 h incubation), and 24.5% (8 h incubation) for the KB disk. The CTX RAST for K. pneumoniae showed 25% (4 h incubation) and 31.3% (4 h incubation) of very major error for the Sensi and KB disks, respectively. CONCLUSIONS: The EUCAST RAST results for E. coli and K. pneumoniae using antimicrobial disks available in Japan suggest their usefulness, although modified RAST breakpoints are required for several antimicrobial agents.

Castalagin and vescalagin purified from leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry: Dual inhibitory activity against PARP1 and DNA topoisomerase II.

Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) is one of the most promising strategies for cancer chemotherapy, and a number of inhibitors possessing nicotinamide-like structures are being developed. To discover new types of PARP1 inhibitors, we screened a large number of substances of plant origin and isolated two inhibitory substances from the leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry. The inhibitory substances were identified as vescalagin and its epimer castalagin by analyses using nuclear magnetic resonance and mass spectrometry. The IC50 of purified vescalagin and castalagin for PARP1 inhibition were 2.67 and 0.86 µM, respectively. Unlike most of synthetic PARP1 inhibitors, castalagin showed a mixed type inhibition, of which Ki was 1.64 µM. When SH-SY5Y cells were treated with these ellagitannins at concentrations of less than 5 µM, cellular poly(ADP-ribosyl)ation was obviously attenuated. Castalagin and vescalagin also possessed inhibitory activity against DNA topoisomerase II, implying that they function as dual inhibitors in cells.