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

Abstract

Two strains of Proteus mirabilis, IpR1 and IpR2, resistant to both imipenem and mecillinam, but susceptible to other beta-lactams were isolated from blood cultures of patients who had been treated with imipenem. Strain IpR1 was isolated in the same sample as a P. mirabilis IpS1 which was susceptible to imipenem and mecillinam. Strains IpR1 and IpR2 did not produce a beta-lactamase and their outer membrane protein profiles were similar to those of IpS1 and P. mirabilis ATCC 29906. Electrophoretic profiles of penicillin-binding proteins (PBPs) showed a decrease in PBP 1A of strains IpR1 and IpR2 compared with IpS1 and ATCC 29906. Competition experiments revealed a decrease in affinity of PBP 2 for imipenem from strain IpR1. These findings suggest that imipenem resistance in P. mirabilis might result from altered PBPs, as reported for Acinetobacter baumanii and Pseudomonas aeruginosa.