Table 1.
Antibacterial agent | MB6476b | MB6477c | MIC differenced | MB6477c ΔmexR (overexpresses MexAB) | MB6477c ΔnfxB (overexpresses MexCD) | MB6477c ΔmexL (overexpresses MexJK) | MB6477c ΔmexZ (overexpresses MexXY) |
---|---|---|---|---|---|---|---|
Imipenem | 16 | 16 | 1-fold | 16 | 4 | 16 | 16 |
IMI/RELe | 1 | 1 | 1-fold | 1 | 0.25 | 1 | 1 |
Ceftazidimef | 1 | 1 | 1-fold | ND | ND | ND | ND |
Aztreonamg | 0.5 | 4 | 8-fold | ND | ND | ND | ND |
Meropenemf | 1 | 1 to 2 | 1- to 2-fold | 16 | 4 | 2 | 2 |
Chloramphenicolg | 2 | > 256 | > 128-fold | ND | ND | ND | ND |
Levofloxacing | 0.0078 | 4 | 512-fold | 8 | 4 | 4 | 4 |
IMI/REL imipenem/relebactam, MIC minimum inhibitory concentration, ND not determined, OprD outer membrane porin D, RND resistance-nodulation-cell division
aMIC values were determined by 2-fold serial broth microdilution
bMB6476 nfxC, Δ [MexAB-OprM] Δ [MexCD-OprJ] Δ [MexXY] Δ [MexJK-OprLL] Δ [MexHI-OpmD] Δ [OpmH]), spontaneous OprD deletion
cMB6477 nfxC, wild-type for other efflux pumps, spontaneous OprD deletion
dRatio between the MIC for MB6477 divided by the MIC for MB6476, for the respective antibacterial agent
eImipenem combined with 4 μg/mL of relebactam
fControl antibacterial agent known to be an RND efflux pump substrate, with susceptibility known to be adversely affected by efflux pump overexpression [49, 50]
gControl antibacterial agent known to be an RND efflux pump substrate, with susceptibility known to be adversely affected even in wild-type P. aeruginosa with baseline efflux pump expression [49, 50]