The algorithms included in most automated systems used for antimicrobial susceptibility testing (e.g., Vitek 2) consider that Escherichia coli isolates resistant to
cefoxitin are AmpC-hyperproducers and, consequently, resistant also to
amoxycillin-
clavulanate. However, a recent study revealed that 30% of E. coli clinical isolates resistant to
cefoxitin remained susceptible in vitro to
amoxycillin-
clavulanate. The aim of the present study was to evaluate the in-vivo efficacy of
amoxycillin-
clavulanate in the treatment of an experimental model of
pneumonia, using two clonally related isolates (with identical repetitive extragenic palindromic sequence (REP)-PCR patterns) of AmpC-non-hyperproducing and OmpF-lacking E. coli (Ec985 and Ec571) that were resistant to
cefoxitin and susceptible to
cefotaxime and
amoxycillin-
clavulanate. MICs were determined using a microdilution technique, and in-vitro bactericidal activity was tested using time-kill assays. The in-vivo efficacy of
amoxycillin,
amoxycillin-
clavulanate and
cefotaxime against both isolates was tested in a murine
pneumonia model using immunocompetent C57BL/6 mice. Ec571 (a TEM-1/2 producer) was resistant to
amoxycillin, whereas Ec985 (a TEM-1/2 non-producer) was susceptible.
Amoxycillin,
amoxycillin-
clavulanate and
cefotaxime were bactericidal for Ec985, and
amoxycillin-
clavulanate and
cefotaxime were bactericidal for Ec571 at different concentrations and time-points, as determined using time-kill assays. Treatment with
amoxycillin,
amoxycillin-
clavulanate and
cefotaxime reduced the bacterial lung concentration of Ec985 compared with non-treated controls (p <0.05), whereas
amoxycillin-
clavulanate and
cefotaxime showed efficacy against Ec571 when compared with the control and
amoxycillin groups (p <0.05). Regardless of the exact underlying mechanism(s) of resistance,
amoxycillin-
clavulanate was effective in the experimental murine model in the treatment of
pneumonia caused by AmpC-non-hyperproducing strains of E. coli resistant to
cefoxitin.