We undertook this study to estimate phagocytic killing by neutrophils (PMNs) of Pseudomonas aeruginosa pre-exposed to sub-inhibitory concentration of Amikacin and Imipenem. In particular, we have isolated bacteria from endotracheal aspirates of post-operative patients mechanically ventilated admitted to an ICU with respiratory failure. PMNs were obtained both from these patients (Group A, n. 6) as well as from subjects submitted to surgery with uncomplicated post-operative period (Group B, n. 8). From specimens tested, 6 strains of Pseudomonas aeruginosa were isolated. Results showed that the rate of killing of bacteria treated with Amikacin was no different from that of untreated bacteria, whichever the source of PMNs, either from Group A or Group B patients. On the other hand, the microbicidal effect on P. aeruginosa exposed to Imipenem was significantly enhanced when PMNs were obtained from Group B patients. In the mixture bacteria, Imipenem and PMNs obtained from Group A the rate of killing was low, similar to the controls without antibiotics. Such a finding suggests a possible impairment of PMNs due to the critical disease and in some way responsible for the host adverse interaction between granulocytes, antibiotics and pathogens. The underlying mechanisms remain to be clarified and further studies are required to understand the possible clinical implications.