Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations

Hervé Dupont; Olivier Gaillot; Anne-Sophie Goetgheluck; Claire Plassart; Jean-Philippe Emond; Marion Lecuru; Nicolas Gaillard; Sarah Derdouri; Baptiste Lemaire; Marion Girard de Courtilles; Vincent Cattoir; Hedi Mammeri

doi:10.1128/AAC.01559-15

DOI: 10.1128/AAC.01559-15

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FIG 1
OMP profiles of representative CNSE isolates compared to wild-type reference strains. OMPs were profiled by SDS-PAGE. Lanes: 1, E. coli porin-deficient strain BH01043; 2, E. coli porin-deficient strain DP02127; 3, E. coli wild-type strain TOP10; 4, E. cloacae porin-deficient strain BH01124; 5, E. cloacae porin-deficient strain AJP01076; 6, E. cloacae wild-type strain ATCC 13047; 7, K. pneumoniae porin-deficient strain AG02123; 8, K. pneumoniae wild-type strain NTUH-K2044. The arrows indicate the positions of the OMPs OmpC and OmpF.

TABLE 1

β-Lactamase production and OMP profiles for the 139 CNSE isolates

OMP profile	Organism with β-lactamase production, β-lactamase(s) (no. of strains)
OMP profile	Carbapenemase	ESBL	AmpC	ESBL + AmpC	No β-lactamase
Wild-type outer membrane profile	E. cloacae, IMI-3 (1)		M. morganii (3)		P. mirabilis (1)
	K. pneumoniae, OXA-48 (1)
Loss of one major outer membrane porin		K. pneumoniae, CTX-M-15 (10)	E. aerogenes (4)	E. cloacae, CTX-M-9/SHV-12 (36)
		E. coli, CTX-M-15 (2)	E. cloacae (39)	E. cloacae, CTX-M-9 (20)
			C. freundii (4)	E. cloacae, SHV-12 (4)
			S. marcescens (1)	C. freundii, CTX-M-9 (1)
			E. coli, ACC-1 (1)
Loss of OmpC-like and OmpF-like porins		K. pneumoniae, CTX-M-15 (1)	K. pneumoniae, CMY-2 (4)	E. cloacae, CTX-M-9/SHV-12 (4)
			S. marcescens (1)	E. aerogenes, TEM-24 (1)

TABLE 2

MIC distributions for the 139 carbapenem-nonsusceptible Enterobacteriaceae clinical isolates, with cumulative percentages

Organism (no. of strains)	Agent(s)^a	MIC (μg/ml) (cumulative %)										MIC₅₀	MIC₉₀
Organism (no. of strains)	Agent(s)^a	≤0.06	0.125	0.25	0.5	1	2	4	8	16	≥32	MIC₅₀	MIC₉₀
E. cloacae (104)	CAZ								2 (2)	3 (5)	99 (100)	≥32	≥32
	CAZ-AVI		9 (9)	21 (29)	58 (85)	12 (96)	4 (100)					0.5	1
	ATM							2 (2)	3 (5)	14 (18)	85 (100)	≥32	≥32
	ATM-AVI		14 (13)	23 (36)	63 (96)	4 (100)						0.5	0.5
	ERTA					82 (79)	12 (90)	5 (93)			5 (100)	1	2
	IMP		5 (5)	8 (13)	76 (86)	10 (95)			4 (99)^b		1 (100)^c	0.5	1
	MERO			11 (11)	79 (87)	9 (95)			4 (99)^b		1 (100)^c	0.5	1
	DORI		18 (17)	71 (86)	9 (94)	1 (95)		4 (99)^b			1 (100)^c	0.25	1
K. pneumoniae (16)	CAZ		1 (6)								15 (100)	≥32	≥32
	CAZ-AVI		3 (19)	8 (69)	1 (75)			4 (100)				0.25	4
	ATM	1 (6)									15 (100)	≥32	≥32
	ATM-AVI	1 (6)	9 (63)	2 (75)				4 (100)				0.125	4
	ERTA					7 (44)	3 (63)	2 (75)			5 (100)^b	2	≥32
	IMP			2 (13)	8 (63)	1 (69)				1 (75)^b	4 (100)^b	0.5	≥32
	MERO				2 (13)	9 (69)				1 (75)^b	4 (100)^b	1	≥32
	DORI			2 (13)	7 (56)	2 (69)			1 (75)^b	4 (100)^b		0.5	16
E. aerogenes (5)	CAZ									1 (20)	4 (100)	≥32	≥32
	CAZ-AVI			2 (40)	2 (80)		1 (100)					0.5	2
	ATM								1 (20)	1 (40)	3 (100)	≥32	≥32
	ATM-AVI		3 (60)	1 (80)		1 (100)						0.25	1
	ERTA						4 (80)				1 (100)^b	2	≥32
	IMP					4 (80)			1 (100)^b			1	8
	MERO					4 (80%)			1 (100)^b			1	8
	DORI			1 (20%)	3 (80%)			1 (100%)^b				0.5	4
E. coli (3)	CAZ						2 (67)				1 (100)	2	≥32
	CAZ-AVI		1 (33)	2 (100)								0.25	0.25
	ATM								2 (66)		1 (100)	8	≥32
	ATM-AVI	1 (33)	1 (67)	1 (100)								0.125	0.25
	ERTA			2 (67)	1 (100)							1	2
	IMP				3 (100)							0.25	0.25
	MERO				3 (100)							0.25	0.25
	DORI			1 (33)	2 (100)							0.25	0.25
C. freundii (5)	CAZ										5 (100)	≥32	≥32
	CAZ-AVI			2 (40)	3 (100)							0.5	0.5
	ATM									4 (80)	1 (100)	16	≥32
	ATM-AVI			4 (80)	1 (100)							0.25	0.5
	ERTA					1 (20)	3 (80)	1 (100)				2	4
	IMP			1 (20)	2 (60)	2 (100)						0.5	1
	MERO				3 (60)	2 (100)						0.5	1
	DORI			3 (60)	1 (80)	1 (100)						0.25	1
S. marcescens (2)	CAZ										2 (100)	≥32	≥32
	CAZ-AVI				1 (50)	1 (100)						0.5	1
	ATM										2 (100)	≥32	≥32
	ATM-AVI			1 (50)		1 (100)						0.25	1
	ERTA					1 (50)					1 (100)^b	1	≥32
	IMP						1 (50)				1 (100)^b	0.5	≥32
	MERO					1 (50)					1 (100)^b	0.25	≥32
	DORI					1 (50)				1 (100)^b		0.25	4
P. mirabilis (1)	CAZ	1 (100)										≤0.06	≤0.06
	CAZ-AVI	1 (100)										≤0.06	≤0.06
	ATM	1 (100)										≤0.06	≤0.06
	ATM-AVI	1 (100)										≤0.06	≤0.06
	ERTA	1 (100)										≤0.06	≤0.06
	IMP								1 (100)			8	8
	MERO	1 (100)										≤0.06	≤0.06
	DORI	1 (100)										≤0.06	≤0.06
M. morganii (3)	CAZ	1 (33)							1 (67)		1 (100)	8	≥32
	CAZ-AVI	1 (33)	1 (67)	1 (100)								0.125	0.25
	ATM	1 (33)	1 (67)						1 (100)			0.125	1
	ATM-AVI	3 (100)										≤0.06	≤0.06
	ERTA	3 (100)										≤0.06	≤0.06
	IMP								2 (67)	1 (100)		8	16
	MERO	3 (100)										≤0.06	≤0.06
	DORI	3 (100)										≤0.06	≤0.06

↵a CAZ, ceftazidime; CAZ-AVI, ceftazidime-avibactam; ATM, aztreonam; ATM-AVI, aztreonam-avibactam; ERTA, ertapenem; IMP, imipenem; MERO, meropenem; DORI, doripenem.
↵b CNSE isolates with a complete loss of OmpC and OmpF porins.
↵c True carbapenemase producers.