Emergence of cross-resistance to imipenem and other beta-lactam antibiotics in Pseudomonas aeruginosa during therapy

Abstract

The emergence of resistance to imipenem and other beta-lactams by Pseudomonas aeruginosa was investigated with two pairs of isolates. Two of these isolates were susceptible to imipenem and other beta-lactam antibiotics, such as moxalactam, ceftriaxone and cefotaxime, while the other two had developed resistance to those antibiotics during imipenem therapy. So far imipenem-resistant isolates have not demonstrated cross-resistance to other beta-lactam agents. We examined in these clinical isolates the possible mechanisms of resistance due to permeability modifications, either in outer membrane proteins (porins) or to LPS (lipopolysaccharides) complex. Particularly we analysed possible modification of physico-chemical properties of outer membrane proteins, such as changes in their hydrophobicity and electrical charge. beta-lactamase production was also studied. Results showed that resistance to imipenem may be related to loss or modifications in hydrophobicity of an outer membrane protein of about 46 Kdal; other modifications concerned hydrophobicity of the porin OMP F and, in one strain, the LPS complex appears to be responsible for resistance to other beta-lactam antibiotics together in combination with the production of beta-lactamases.