MEROPENEM RESISTANCE IN PSEUDOMONAS-AERUGINOSA

Two genetically distinct classes of meropenem-low-susceptibility Pseud omonas aeruginosa PA02152 mutants, which arose spontaneously, were iso lated, Two meropenem resistance genes, mpmA and mpmB, were mapped near ilvB/C and proC, respectively, on the P. aeruginosa PAO chromosome. T he mpm4 was thought to be identical to oprD2 because of the cross-resi stance to carbapenems and the association with the loss of the outer m embrane protein D2 (OprD2). The mpmB mutation conferred a 4-fold incre ase in resistance to meropenem, and cross-resistance to various types of antimicrobial agents, e.g. carbenicillin, norfloxacin and chloramph enicol. However, the mpmB mutant was susceptible to imipenem. This mut ant still possessed OprD2 and showed increased expression of a 48-kD o uter membrane protein, although its profiles of beta-lactamase activit y and affinities of penicillin-binding proteins for beta-lactams were indistinguishable from those of the parent strain. The resistance gene mpmB was considered to be an allele of nalB (or cfxB or oprK) from th e results of the transductional analysis. The mutation frequency of mp mA:mpmB was in the ratio of 4:1. The same results were obtained in ano ther clinically isolated P. aeruginosa strain. Meropenem resistance ca used by both mpmA and mpmB mutations seemed to be due to the reduction in permeability of antibiotics through the outer membrane. These find ings suggest a new pathway for the translocation of meropenem other th an that mediated by OprD2 across the outer membrane. Thus, meropenem s howed about 4- to 8-fold higher activity than imipenem against OprD2-d eficient P. aeruginosa.