Imipenem resistance of enterobacter aerogenes mediated by outer membrane permeability

Abstract

Multidrug-resistant Enterobacter aerogenes strains are increasingly isolated in Europe and especially in France. Treatment leads to imipenem resistance, because of a lack of porin. We studied the evolution of resistance in 29 strains isolated from four patients during their clinical course. These strains belonged to the prevalent epidemiological type observed in France in previous studies (C. Bosi, et al., J. Clin. Microbiol. 37:2165-2169, 1999; A. Davin-Regli et al., J. Clin. Microbiol. 34:1474-1480, 1996). They also harbored a TEM-24 extended-spectrum beta-lactamase-coding gene. Thirteen strains were susceptible to gentamicin and resistant to imipenem and cefepime. All of the patients showed E. aerogenes strains with this resistance after an imipenem treatment. One patient showed resistance to imipenem after a treatment with cefpirome. Twelve of these 13 strains showed a lack of porin. Cessation of treatment with imipenem for three patients was followed by reversion of susceptibility to this antibiotic and the reappearance of porins, except in one case. For one patient, we observed three times in the same day the coexistence of resistant strains lacking porin and susceptible strains possessing porin. The emergence of multidrug-resistant E. aerogenes strains is very disquieting. In our study, infection by E. aerogenes increased the severity of the patients' illnesses, causing a 100% fatality rate.

FIG. 1

Clinical courses of patients 1, 2, 3, and 4. Shaded bars indicate patient treatment. Nb, number; ND, not done; +, present; −, absent; S, susceptible; R, resistant.

FIG. 2

RAPD fingerprints of the 16 isolates of patient 3 (8) and patient 4 (8). Lane M, molecular weight marker (marker VI). The lane numbers are isolate designations.

FIG. 3

Immunodetection of E. aerogenes outer membrane proteins. Immunostaining was done with polyclonal antibodies directed against the OmpF monomer or OmpC. PMY150 (P) and BZB1107 (B) were used as positive and negative samples, respectively. Isolates 2, 5, 7, 9, 11, and 12 from patients 1 (a) and 2 (b) presented porin-deficient phenotypes. The arrows indicate the postulated porin migration (34 kDa). The lane numbers are isolate designations.