In vitro studies evaluating the activity of imipenem in combination with relebactam against Pseudomonas aeruginosa

Table 1 Antibiogram of the OprD-deficient P. aeruginosa efflux mutant isogenic strain set showing MICs (μg/mL)^a

Antibacterial agent	MB6476^b	MB6477^c	MIC difference^d	MB6477^c ΔmexR (overexpresses MexAB)	MB6477^c ΔnfxB (overexpresses MexCD)	MB6477^c ΔmexL (overexpresses MexJK)	MB6477^c ΔmexZ (overexpresses MexXY)
Imipenem	16	16	1-fold	16	4	16	16
IMI/REL^e	1	1	1-fold	1	0.25	1	1
Ceftazidime^f	1	1	1-fold	ND	ND	ND	ND
Aztreonam^g	0.5	4	8-fold	ND	ND	ND	ND
Meropenem^f	1	1 to 2	1- to 2-fold	16	4	2	2
Chloramphenicol^g	2	> 256	> 128-fold	ND	ND	ND	ND
Levofloxacin^g	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]

ISSN: 1471-2180