Oxygen-dependent differences in exopolysaccharide production and aminoglycoside inhibitory-bactericidal interactions with Pseudomonas aeruginosa—implications for endocarditis

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Abstract
Antibiotic-induced growth inhibition and killing of a non-mucoid strain of Pseudomonas aeruginosa (PA-96) in vitro and ex vivo were studied at oxygen tensions approximating those of the right and left cardiac ventricles in vivo (pO2 = 40 VS. 80 mm Hg). This pseudomonal strain grew equally at the two oxygen tensions, yet only bacteria exposed to pO2 80 mm Hg revealed significant exopolysaccharide production as shown by PAS and ruthenium red staining. Similarly, scanning electron microscopy of pseudomonal cells within aortic (but not tricuspid) vegetations revealed surface excrescenses compatible with surrounding exopolysaccharide (glycocalyx). Amikadn at 10 × MIC caused significantly less in-vitro killing of pseudomonal cells at pO2 80 VS. 40 mm Hg. In vitro and ex vivo (within experimental aortic and tricuspid vegetations), post-antibiotic effect durations were about 50% shorter for cells exposed to amikacin at pO2 80 mm Hg than 40 mm Hg. These data demonstrate suboptimal aminoglycoside-induced growth inhibition and lulling, as well as enhanced exopolysaccharide production of a non-mucoid P. aeruginosa strain at oxygen tensions reflective of the left side of the heart. These findings may in part explain the better results seen in aminoglycoside-treated right compared to left-sided pseudomonal endocarditis in man.