TABLE 1.
Avibactam potentiation of ceftazidime action is eliminated by β-lactamase GES-14 mutationsa
| Gen+e | Mutation | Product | Ceftazidime MIC (μg/mL) |
ΔMIC | |
|---|---|---|---|---|---|
| –avibactam | +avibactam | ||||
| – | None | – | >2,048 | 14 ± 2 | >146 |
| trpB | Insertions | >2,048 | 12 | >170 | |
| bla GES-14 | Deletion | β-Lactamase GES-14 | 11 ± 2 | 7.5 ± 1 | 1.5 |
| lptE | Insertions | LOS transport | 136 ± 57 | 0.9 ± 0.2 | 151 |
| dsbA | Insertions | Thiol:disulfide interchange | 717 ± 108 | 12 ± 5 | 59 |
| gidA | Insertions | Division | >2,048 | ||
| bla OXA-23 | Deletion | β-Lactamase OXA-23 | >2,048 | 12 | >170 |
| blaGES-14, blaOXA-23 | Deletions | β-Lactamases GES-14 and OXA-23 | 12 | 8 | 1.2 |
a
Mutants were assayed for ceftazidime sensitivity in the presence and absence of avibactam (64 μg/mL). The values reflect 4 to 13 independent efficiency of plating assays of multiple alleles, and nonzero sample standard deviations are shown. The trpB mutants serve as wild-type transposon-containing strains. A deletion mutant lacking resistance island 2, which includes blaGES-14, gave MIC values comparable to the ΔblaGES-14 single mutant (not shown). LOS, lipooligosaccharide; MIC, minimal growth inhibitory concentration