The respected art historian Antonio Morassi, as a student under Max Dvořák in Vienna in 1912–16, wrote a thesis on the Renaissance architect Michele Sanmicheli (1487–1559), who was active in Verona ...and Venice. This, later, formed the basis of an article that was intended for publication but never surfaced, and the thesis and putative article form the subjects of a new book (Giulio Zavatta, Il Michele Sanmicheli di Antonio Morassi, Treviso: Zel, 2022). The book explores Morassi’s thesis in the context of his experience of the emerging discipline of art history in Vienna, while the thesis reveals itself to be particularly well conceived and informative, and also remarkably prescient of later ways of thinking about Sanmicheli and his architecture.
•Aztreonam-based therapies are key for treatment of metallo-β-lactamase-producing bacteria.•VIM-2 Pseudomonas aeruginosa was studied over 7 days in the hollow fibre infection model.•Aztreonam is ...associated with creation of bacterial filaments through inhibition of septation.•Time-lapse imaging showed filaments fragmenting into many rods after drug removal.
The proliferation of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa represents a significant public health threat. P. aeruginosa undergoes significant phenotypic changes that drastically impair antibiotic efficacy. The objectives of this study were (1) to quantify the time-course of killing of VIM-2-producing P. aeruginosa in response to aztreonam-based therapies (including avibactam for coverage of AmpC), and (2) to document the capacity of P. aeruginosa to undergo morphological transformations that facilitate persistence.
A well-characterised, clinical VIM-2-producing P. aeruginosa was studied in the hollow fibre infection model (HFIM) over 9 days (7 days of active antibiotic therapy, 2 days of treatment withdrawal) at a 107.5 CFU/mL starting inoculum. HFIM treatment arms included: growth control, aztreonam, ceftazidime/avibactam, aztreonam/ceftazidime/avibactam, polymyxin B, and aztreonam/ceftazidime/avibactam/polymyxin B. In addition, real-time imaging studies were conducted under static conditions to determine the time course of the reversion of persister cells.
There was a pronounced discrepancy between OD620 and bacterial counts obtained from plating methods (hereafter referred to as ‘OD-count discrepancy’). For aztreonam monotherapy, observed counts were 0 CFU/mL by 120 h. Despite this, there was a significant OD-count discrepancy compared with the pre-treatment 0 h. Between therapy withdrawal at 168 h and 216 h, all arms with suppressed counts had regrown to the system-carrying capacity. Real-time imaging of the P. aeruginosa filaments after drug removal showed rapid reversion from a long, filamentous phenotype to many individual rods within 2 h.
Managing MBL-producing P. aeruginosa requires a multifaceted approach, focused on maximising killing and minimising proliferation of resistant and persistent subpopulations, which will involve eliminating drug-induced phenotypic transformers.
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