In vivo selection of Enterobacter aerogenes with reduced susceptibility to cefepime and carbapenems associated with decreased expression of a 40 kDa outer membrane protein and hyperproduction of AmpC beta-lactamase.

The mechanism(s) of resistance or decreased susceptibility to cefepime (FEP) and/or imipenem (IMP) in three consecutive isolates of Enterobacter aerogenes (Ea1, Ea2 and Ea3) cultured from bronchial aspirates of the same patient after treatment with ceftriaxone and FEP were studied. Identification was performed with the VITEK 2 system. All three isolates showed identical pulsed-field gel electrophoresis patterns and were resistant (minimum inhibitory concentrations (MICs)) to cefoxitin (MIC, >1024 mg/L), cefotaxime (CTX; MIC, 32-128 mg/L) and ceftazidime (CAZ; MIC, 32-128 mg/L) but susceptible to meropenem (MIC, Glu. Three outer membrane proteins (OMPs) of 51 kDa, 40 kDa and 38 kDa were observed in the three isolates by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) (10% polyacrylamide gels with 4 M urea), although expression of the 40 kDa OMP was reduced in Ea2. In conclusion, decreased susceptibility to FEP and IMP in Ea2 is related to reduced expression of a 40 kDa OMP and hyperproduction of AmpC, whereas resistance to FEP in Ea3 is associated with hyperproduction of an altered AmpC.