%0 Journal Article %A Tzouvelekis, L. S. %A Tzelepi, E. %A Kaufmann, M. E. %A Mentis, A. F. %T Consecutive mutations leading to the emergence in vivo of imipenem resistance in a clinical strain of Enterobacter aerogenes %D 1994 %J Journal of Medical Microbiology, %V 40 %N 6 %P 403-407 %@ 1473-5644 %R https://doi.org/10.1099/00222615-40-6-403 %I Microbiology Society, %X Summary Three consecutive isolates of Enterobacter aerogenes 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 β-lactamase was obtained, and therapy was altered to a new combination which included imipenem. During this course of treatment, a strain of E. aerogenes was isolated that was resistant to virtually all β-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 ampD allele prevented cephalosporinase production and restored β-lactam susceptibility in the imipenem-resistant isolate. It was concluded that stable derepression of class-I β-lactamase production and reduced permeability are both required for expression of imipenem resistance in E. aerogenes, and that previous exposure to cephalosporins may encourage the emergence of such strains. %U https://www.microbiologyresearch.org/content/journal/jmm/10.1099/00222615-40-6-403