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Spread of multidrug-resistant Pseudomonas aeruginosa strains threatens to render currently available antibiotics obsolete, with limited prospects for the development of new antibiotics. Lytic bacteriophages (phages), the natural predators of bacteria, represent a path to combat this threat. In vitro directed evolution is traditionally applied to expand the phage host range or increase bacterial suppression in planktonic cultures. However, while 80% of human microbial infections are biofilm-associated, research towards targeted improvement of phages’ ability to combat biofilms remains scarce. Here, we describe an in vitro evolution assay that improves multiple phage parameters in parallel, while optimizing phage cocktail design by exploiting a bacterial phage resistance trade-off. The obtained evolved phages show an expanded host spectrum, improved antimicrobial efficacy under isothermal microcalorimetric monitoring and enhanced antibiofilm performance, as determined by RT-qPCR. Our two-phage cocktail revealed further improved antimicrobial efficacy without incurring dual-phage-resistance in treated bacteria. We anticipate this assay will allow a better understanding of phenotypic-genomic relationships in phages and enable the training of phages against other desired pathogens. This, in turn, will strengthen phage therapy as a treatment adjunct to improve clinical outcomes of multidrug-resistant bacterial infections.

Recurrence of cavernous venous malformation is exceedingly rare. In 1995, a 16-year-old woman was referred for left axial proptosis. Her left visual acuity was 20/200, and there were choroidal folds in the OS. MRI studies showed a well-circumscribed retrobulbar intraconal mass in the left orbit. The tumor was totally removed with intact capsule through a transconjunctival orbitotomy and proved to be a cavernous venous malformation. In 2020, at the age of 41 years and 25 years after the operation, she again presented with left proptosis. Imaging results were very similar to those at first presentation. This tumor was also extirpated in its entirety via an inferior forniceal orbitotomy with the histopathologic diagnosis of a cavernous venous malformation. Her final left visual acuity remained 20/50. Women with orbital cavernous venous malformations, especially those who undergo surgical removal at a relatively young age are advised to have long-term follow up complemented with occasional imaging studies.