Impact of derepressed AmpC beta-lactamase ACT-9 on the clinical efficacy of ertapenem.

An in vivo development of Pantoea agglomerans mutants (isolates PA2 to PA4) with reduced ertapenem susceptibility from that of isolate PA1 was associated with an inadequate clinical response to ertapenem therapy. All four isolates harbored the bla(ACT-9) AmpC β-lactamase gene. However, a loss-of-function mutation in the ampD gene in PA2 to PA4, but not PA1, led to derepressed ACT-9. The reduced ertapenem susceptibility caused by derepressed ACT-9 was confirmed with an ampD knockout mutant of PA1.