Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins

Abstract
Two strains of Proteus mirabilis, IpRl and IpR2, resistant to both imipenem and mecillinam, but susceptible to other βMactams were isolated from blood cultures of patients who had been treated with imipenem. Strain IpRl was isolated in the same sample as a P. mirabilis IpSl which was susceptible to imipenem and mecillinam. Strains IpRl and IpR2 did not produce a β-lactamase and their outer membrane protein profiles were similar to those of IpSl and P. mirabilis ATCC 29906. Electrophoretic profiles of penicillin-binding proteins (PBPs) showed a decrease in PBP 1A of strains IpRl and IpR2 compared with IpSl and ATCC 29906. Competition experiments revealed a decrease in affinity of PBP 2 for imipenem from strain IpRl. These findings suggest that imipenem resistance in P. mirabilis might result from altered PBPs, as reported for Acinetobacter baumanii and Pseudomonas aeruginosa.