Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1-producing Enterobacteriaceae using a hollow-fibre infection model.

BACKGROUND: MBL-producing strains of Enterobacteriaceae are a major public health concern. We sought to define optimal combination regimens of ceftazidime/avibactam with aztreonam in a hollow-fibre infection model (HFIM) of MBL-producing strains of Escherichia coli and Klebsiella pneumoniae. METHODS: E. coli ARLG-1013 (blaNDM-1, blaCTX-M, blaCMY, blaTEM) and K. pneumoniae ARLG-1002 (blaNDM-1, blaCTXM-15, blaDHA, blaSHV, blaTEM) were studied in the HFIM using simulated human dosing regimens of ceftazidime/avibactam and aztreonam. Experiments were designed to evaluate the effect of staggered versus simultaneous administration, infusion duration and aztreonam daily dose (6 g/day versus 8 g/day) on bacterial killing and resistance suppression. Prospective validation experiments for the most active combination regimens were performed in triplicate to ensure reproducibility. RESULTS: Staggered administration of the combination (ceftazidime/avibactam followed by aztreonam) was found to be inferior to simultaneous administration. Longer infusion durations (2 h and continuous infusion) also resulted in enhanced bacterial killing relative to 30 min infusions. The rate of killing was more pronounced with 8 g/day versus 6 g/day aztreonam combination regimens for both tested strains. In the prospective validation experiments, ceftazidime/avibactam with aztreonam dosed every 8 and 6 h, respectively (ceftazidime/avibactam 2/0.5 g every 8 h + aztreonam 2 g every 6 h), or ceftazidime/avibactam with aztreonam as continuous infusions resulted in maximal bacterial killing and resistance suppression over 7 days. CONCLUSIONS: Simultaneous administration of aztreonam 8 g/day given as a continuous or 2 h infusion with ceftazidime/avibactam resulted in complete bacterial eradication and resistance suppression. Further study of this combination is needed with additional MBL-producing Gram-negative pathogens. The safety of this double ß-lactam strategy also warrants further study in Phase 1 clinical trials.

Look who's talking: recognizing friends from visible articulation.

We tested whether isolated visible articulatory information can be used for identifying familiar speakers. A facial point-light methodology was used to isolate the visible articulation of seven speakers. These point-light video clips were then shown to nine participants who had long-term personal interactions with the speakers. Results revealed that participants could identify the speakers at better than chance levels when the faces were shown articulating, but not when the faces were shown without movement. The results indicate that visible articulatory information can be used to identify speakers.

Hearing a face: cross-modal speaker matching using isolated visible speech.

An experiment was performed to test whether cross-modal speaker matches could be made using isolated visible speech movement information. Visible speech movements were isolated using a point-light technique. In five conditions, subjects were asked to match a voice to one of two (unimodal) speaking point-light faces on the basis of speaker identity. Two of these conditions were designed to maintain the idiosyncratic speech dynamics of the speakers, whereas three of the conditions deleted or distorted the dynamics in various ways. Some of these conditions also equated video frames across dynamically correct and distorted movements. The results revealed generally better matching performance in the conditions that maintained the correct speech dynamics than in those conditions that did not, despite containing exactly the same video frames. The results suggest that visible speech movements themselves can support cross-modal speaker matching.