TABLE 3.

Effects of intrinsic resistance mechanisms on xeruborbactam MICs in clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae

Strain	Beta-lactamases	OmpK35a		OmpK36a		MIC (μg/mL) of:
		Description	Functional status	Description	Functional status	Xeruborbactam	Tigecyclineb
Escherichia coli strains
EC1081	CTX-M-15, OXA-1	Full length	FN	Full length	FN	8	0.5
EC1085	None	Full length	FN	Full length	FN	8	0.25
EC1121	CMY-6, CTX-M-15, NDM-1, OXA-2, TEM-1B-like	FS from aa 31	NF	Full length	FN	8	0.25
EC1088	KPC-3, OXA-9, TEM-1A	Full length	FN	Full length	FN	8	0.125
EC1097	KPC-3, TEM-1B	Full length	FN	Full length	FN	8	1
EC1098	CMY-6, NDM-1, OXA-2, TEM-1A-like	FS from aa 31	NF	Full length	FN	8	1
EC1078	CMY-2, CTX-M-14, TEM-1B	FS from aa 251	NF	E130stop	NF	32	0.5
EC1119	CTX-M-15 OXA-1	FS from aa 213	NF	IS1414 at nt 756	NF	32	4
Klebsiella pneumoniae strains
KP1070	KPC-2, SHV-11, SHV-12, TEM-1	FS from aa 42	NF	Full length	FN	8	1
KP1274	SHV-30, VIM-1	Full length	FN	Full length	FN	8	1
KP1004	KPC-2, TEM-1, SHV-11	FS from aa 42	NF	Full length	FN	16	1
KP1251	KPC-3 TEM SHV	FS from aa 42	NF	Full length, R191L	FN	16	1
KP1074	KPC-3, SHV-11, TEM-1	FS from aa 42	NF	GD	PFN	32	0.5
KP1093	KPC-3 TEM-1 SHV-11	FS from aa 42	NF	GD	PFN	32	1
KP1463	KPC-2, CTX-M-65, TEM-1, SHV-11	FS from aa 29	NF	TGA at aa 94	NF	64	1
KP1598	KPC-2, SHV-11, CTX-M-14	FS from aa 29	NF	GD	PFN	64	4
KP1469	KPC-33, CTX-M-15, OXA-1, TEM-1, SHV-28	Full length, low expression	NF	FS from aa 5	NF	64	4
Enterobacter cloacae strains
ECL1126	KPC-2, TEM	Full length	FN	Full length	FN	16	2
ECL1131	KPC-4, TEM, OXA-1	FS from aa 19	NF	Full length	FN	16	2
ECL1057	NDM-1, TEM-1, CTX-M-15	Full length	FN	FS at aa 210	NF	64	8
ECL1079	KPC-3, TEM	Q60stop	NF	TAA at codon 78	NF	64	4

^aaa, amino acid; FS, frameshift; GD, insertion of two amino acids, Gly134Asp135, in the L3 loop of OmpK36, resulting in a partially functional OmpK36 with a constricted channel; FN, functional; NF, nonfunctional; nt, nucleotide; PFN, partially functional.

^bIncreased tigecycline MIC values are associated with regulatory mutations that simultaneously decrease the expression of ompK35 and increase efflux by the AcrAB-TolC efflux pump (21, 22).