Failure of Therapy in Pseudomonas Endocarditis: Selection of Resistant Mutants

Despite optimal use of available antibacterial agents, endocarditis due to Pseudomonas aeruginosa is commonly associated with poor response to medical treatment. Two patients are described in whom emergence of resistance to beta-lactam antibiotics was associated with clinical failure. A subpopulation of resistant mutants (10(-7)) was found within the initial, apparently sensitive population of bacteria. These resistant mutants were similar to posttherapy isolates in their increased production of beta-lactamase and in their identical pattern of resistance to beta-lactam antibiotics. Moreover, the only beta-lactamase produced was type Id, and this enhanced production proved to be constitutive. A relatively large inoculum (10(6) colony-forming units/g of tissue) of bacteria was found postoperatively in the heart valves of both patients. The failure to respond is postulated to be due to the selection of these producers of high levels of beta-lactamase in a large bacterial inoculum.