Pretreatment of Pseudomonas aeruginosa with a sub-MIC of imipenem enhances bactericidal activity of neutrophils.

Abstract

The influence of the pretreatment of Pseudomonas aeruginosa strain O1 (PAO-1) with a sub-minimum inhibitory concentration (MIC) of imipenem on bactericidal activity, phagocytosis, the production of oxygen radical intermediates, and the induction of apoptosis in murine peritoneal neutrophils, as well as the catalase activity in the bacteria in comparison with that of ceftazidime-treated bacteria were studied. Bacteria treated with imipenem at (1/4) MIC were killed at significantly higher rates by neutrophils than ceftazidime-treated and nontreated bacteria. However, antibiotic-treated bacteria showed similar numbers of bacteria-phagocytized neutrophils to those in untreated bacteria. Imipenem pretreatment of bacteria led to an increase in the production of oxygen radical intermediates by neutrophils and the inhibition of neutrophilic apoptosis following incubation, whereas these features did not occur in neutrophils incubated with nontreated and ceftazidime-treated bacteria. The catalase activity of bacteria was not suppressed by pretreatment with either antibiotic at (1/4) MIC. These findings suggest that the exposure of P. aeruginosa to a sub-MIC of imipenem enhances the susceptibility of the bacteria to neutrophilic killing and effectively modifies the physiological activities of neutrophils, but does not decrease bacterial catalase activity. These actions may account for the postantibiotic leukocyte enhancement (PALE) effect of a sub-MIC of imipenem in the host.