Consecutive mutations leading to the emergence of imipenem resistance in a clinical strain of Free

Abstract

Summary

Three consecutive isolates of were obtained from the blood cultures of a hospitalised patient who was receiving antibiotic therapy. The initial isolate possessed an inducible cephalosporinase and was susceptible to third-generation cephalo-sporins. After ceftazidime treatment, a second isolate resistant to this antibiotic and characterised by stable overproduction of the chromosomal -lactamase was obtained, and therapy was altered to a new combination which included imipenem. During this course of treatment, a strain of . was isolated that was resistant to virtually all -lactam agents including imipenem. Comparison of biotypes and ribotyping profiles indicated that the three isolates were probably derived from a single strain which had undergone several mutations during antibiotic exposure. Examination of outer-membrane protein (OMP) preparations and lipopolysaccharide (LPS) profiles showed that the imipenem-resistant isolate lacked a major OMP and high molecular mass LPS. Furthermore, this isolate displayed reduced permeability to cephaloridine compared with the initial isolate. The introduction of a plasmid carrying a wild-type allele prevented cephalosporinase production and restored -lactam susceptibility in the imipenem-resistant isolate. It was concluded that stable derepression of class-I -lactamase production and reduced permeability are both required for expression of imipenem resistance in . , and that previous exposure to cephalosporins may encourage the emergence of such strains.

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1994-06-01
2024-03-28
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