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(A) Therapeutic concentrations of antibiotics are unable to penetrate biofilms due to poor permeability and depressed metabolism of biofilm constituents. Phage OMKO1, however, is able to replicate within bacteria present in biofilm. Next, biofilm instability occurs as phage OMKO1 replicates. Finally, with the biofilm disrupted, therapeutic concentrations of antibiotic can better reach target bacteria, and any cells resistant to phage OMKO1 infection are expected to be more susceptible to antibiotics (i.e., less capable of efflux). (B) Mean densities of bacteria previously grown for 72-h as biofilms on Dacron sections, following 24-h exposure to either ciprofloxacin or ceftazidime with and without phage OMKO1. (C) Mean densities of bacteria previously grown for 72-h as biofilms on Dacron sections, following 24-h exposure to differing amounts of phage OMKO1. The black horizontal line represents density equal to the reliable limit of detection (OD600 = 0.1). See text for details
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This strategy was further supported by data in the current study (Fig. 2B and C) that used the strain isolated from the fistular discharge and confirmed re-sensitization to antibiotic in bacteria with evolved resistance to phage OMKO1. This administered titer was determined to be acceptable and to likely exceed the minimum MOI capable of effectively reducing 72-h-old biofilms of the fistular-discharge strain in preliminary bactericidal titer assays (Fig. 2C), although the exact MOI at time of treatment was unknowable.
(A) Intraoperative photograph showing aortic graft and P. aeruginosa infection (arrow) over myocardium, taken during operation to debride and to wash out infected tissues. (B) Comparative CT image showing infected collection (arrow) and site of targeted aspiration during therapy
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This was complicated by a P. aeruginosa mediastinal and aortic graft infection (confirmed by blood and deep wound culture) for which the patient returned to the operating room on multiple occasions for debridement and washout of the infected chest wall (Fig. 3A). CT imaging during the patient's admission in October of 2013 showed increased perigraft fluid near the aortic root with surrounding phlegmonous changes in continuation with the mediastinal fistula tract (Fig. 3B).