Activity of oral β-lactams, tebipenem and ceftibuten, combined with novel oral β-lactamase inhibitors against broad-spectrum β-lactamase-producing Escherichia coli.

Oral ceftibuten and tebipenem, alone or combined with avibactam, ledaborbactam, or xeruborbactam, were evaluated against recombinant Escherichia coli producing 57 acquired β-lactamases. Tebipenem showed greater intrinsic activity than ceftibuten against extended-spectrum β-lactamase (ESBL) and AmpC producers. Whereas avibactam and ledaborbactam remained inactive against metallo-β-lactamases, xeruborbactam restored activity against most class B producers. Tebipenem-xeruborbactam demonstrated the broadest inhibitory spectrum and the lowest MIC values overall. This combination may represent a promising oral option for complicated urinary tract infections.