TABLE 3.
Distributions of meropenem-QPX7728 against characterized strains of Acinetobacter according to the presence of PBP3 and efflux mutationsa
| Strain (drug[s]) | % inhibited at a MIC (μg/ml) of: |
MIC50 (μg/ml) | MIC90 (μg/ml) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ≤0.06 | 0.125 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | 16 | 32 | 64 | >64 | |||
| All (n = 130) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.2 | 7.7 | 15.4 | 31.5 | 76.9 | 100.0 | 64 | >64 |
| W/QPX 4 μg/ml | 3.1 | 4.6 | 8.5 | 17.7 | 34.6 | 63.1 | 83.1 | 96.9 | 100.0 | 100.0 | 100.0 | 100.0 | 2 | 8 |
| W/QPX 8 μg/ml | 5.4 | 9.2 | 19.2 | 32.3 | 49.2 | 74.6 | 86.2 | 96.9 | 100.0 | 100.0 | 100.0 | 100.0 | 2 | 8 |
| PBP3 mutation positive (n = 47) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6 | 12.8 | 21.3 | 40.4 | 95.7 | 100.0 | 64 | 64 |
| W/QPX 4 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 4.3 | 25.5 | 57.4 | 91.5 | 100.0 | 100.0 | 100.0 | 100.0 | 4 | 8 |
| W/QPX 8 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 6.4 | 34.0 | 61.7 | 91.5 | 100.0 | 100.0 | 100.0 | 100.0 | 4 | 8 |
| PBP3 mutation negative (n = 83) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 3.6 | 4.8 | 12.0 | 26.5 | 66.3 | 100.0 | 64 | >64 |
| W/QPX 4 μg/ml | 4.8 | 7.2 | 13.3 | 27.7 | 51.8 | 84.3 | 97.6 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 1 | 4 |
| W/QPX 8 μg/ml | 8.4 | 14.5 | 30.1 | 50.6 | 73.5 | 97.6 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 0.5 | 2 |
| AdeN NF (n = 64) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.3 | 9.4 | 15.6 | 28.1 | 79.7 | 100.0 | 64 | >64 |
| W/QPX 4 μg/ml | 1.6 | 1.6 | 3.1 | 9.4 | 20.3 | 51.6 | 75.0 | 93.8 | 100.0 | 100.0 | 100.0 | 100.0 | 2 | 8 |
| W/QPX 8 μg/ml | 3.1 | 6.3 | 9.4 | 20.3 | 35.9 | 65.6 | 78.1 | 93.8 | 100.0 | 100.0 | 100.0 | 100.0 | 2 | 8 |
| AdeN F (n = 41) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.3 | 7.3 | 9.8 | 24.4 | 73.2 | 100.0 | 64 | >64 |
| W/QPX 4 μg/ml | 4.9 | 9.8 | 17.1 | 34.1 | 58.5 | 70.7 | 87.8 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 1 | 8 |
| W/QPX 8 μg/ml | 9.8 | 17.1 | 36.6 | 58.5 | 68.3 | 80.5 | 92.7 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 0.5 | 4 |
| PBP3 mutation positive AdeN NF (n = 26) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 7.7 | 11.5 | 15.4 | 26.9 | 92.3 | 100.0 | 64 | 64 |
| W/QPX 4 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 3.8 | 11.5 | 46.2 | 84.6 | 100.0 | 100.0 | 100.0 | 100.0 | 8 | 16 |
| W/QPX 8 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 7.7 | 19.2 | 46.2 | 84.6 | 100.0 | 100.0 | 100.0 | 100.0 | 8 | 16 |
| PBP3 mutation positive AdeN F (n = 11) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.1 | 9.1 | 9.1 | 27.3 | 100.0 | 100.0 | 64 | 64 |
| W/QPX 4 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.1 | 54.5 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 4 | 8 |
| W/QPX 8 μg/ml | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 27.3 | 72.7 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 4 | 8 |
| PBP3 mutation negative AdeN F (n = 30) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.7 | 6.7 | 10.0 | 23.3 | 63.3 | 100.0 | 64 | >64 |
| W/QPX 4 μg/ml | 6.7 | 13.3 | 23.3 | 46.7 | 80.0 | 93.3 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 1 | 2 |
| W/QPX 8 μg/ml | 13.3 | 23.3 | 50.0 | 80.0 | 93.3 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 0.25 | 1 |
| PBP3 mutation negative AdeN NF (n = 37) | ||||||||||||||
| MER alone | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.7 | 5.4 | 13.5 | 27.0 | 70.3 | 100.0 | 64 | 65 |
| W/QPX 4 μg/ml | 2.7 | 2.7 | 5.4 | 16.2 | 32.4 | 78.4 | 94.6 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 2 | 4 |
| W/QPX 8 μg/ml | 5.4 | 10.8 | 16.2 | 35.1 | 56.8 | 97.3 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 1 | 2 |
Five NDM-containing strains were excluded from the analysis. For the purpose of the analysis, PBP3 mutations were considered to potentially affect the meropenem-QPX7728 MIC (i.e., significant mutations) if they were present only in the strains with meropenem-QPX7728 MICs of ≥1 μg/ml; 83 strains contained either unaltered PBP3 (compared to the genome of ATCC 19606 [PBP3 negative]) or PBP3 with nonsignificant mutations (present in the strains with MICs of <1 μg/ml), 47 strains contained PBP3 with significant mutations, including H307Y (PBP3 positive) (see Table S2). AdeN was considered nonfunctional if nonsense or frameshift mutations or insertions were found in the adeN gene (n = 64). Strains containing AdeN with amino acid substitutions due to missense mutations were excluded from the analysis.