Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints

Figures & data

Table 1. Comparison of EUCAST and CLSI interpretive criteria for Enterobacterales.

	Broth micro dilution, mg/L			Disc diffusion, mm
	S	I	R	S	I	R	ATU
EUCAST	≤2	NA	>2	≥22	NA	<22	18-22
CLSI	≤4	8	≥16	≥16	12–15	≤11	NA

S: susceptible; I: intermediate; R: resistant; ATU: area of technical uncertainty; NA: not available

Figure 1. Box plot graph of cefiderocol inhibition zone diameter according to carbapenem resistance mechanism. S: susceptible.

Table 2. Cefiderocol inhibition zone diameter according to the carbapenemase type.

		Disc zone diameter, mm			EUCAST interpretive criteria, n (%)
	Number	Median	IQR	Range	S	R	ATU
OXA-48-like	145	24	23–26	13–30	118 (81)	27 (19)	30 (21)
OXA-48	64	25	23–27	13–29	55 (86)	9 (14)	10 (16)
OXA-232	59	23	21–25	17–28	44 (75)	15 (25)	18 (31)
OXA-244	17	24	24–25	16–27	16 (94)	1 (6)	0
OXA-181	5	23	18–28	18–30	3 (60)	2 (40)	2 (40)
MBL^a	42	18	15–21	6–26	8 (19)	34 (81)	16 (38)
MBL with OXA-48- like^b	31	17	14–21	6–26	5 (16)	26 (84)	10 (32)
MBL single	11	20	18–23	14–26	3 (27)	8 (73)	6 (55)
KPC	4	25	22–26	19–26	3 (75)	1 (25)	1 (25)
No-carbapenemase	13	26	24–27	17–29	11 (85)	2 (15)	1 (7)
Carbapenem susceptible	50	28	26–28	21–27	48 (98)	2 (2)	1 (2)
Total	254	24	24–26	6–37	189 (74)	65 (26)	49 (19)

^aNDM (n = 41) and VIM (n = 1); ^bOXA-48 (n = 27), OXA-232 (n = 3), OXA-244 (n = 1); IQR: interquartile range; MBL: metallo-beta-lactamase; CRK; carbapenem resistant Klebsiella spp.; ATU: area of technical uncertainty.

Table 3. Comparison of interpretive categories when using EUCAST and CLSI inhibition zone diameter breakpoints for cefiderocol according to carbapenem resistance mechanism.

Carbapenem resistance mechanism	Number of isolates	R (%)		I (%)	S (%)
		EUCAST	CLSI	CLSI	EUCAST	CLSI
OXA-48-like	145	27 (19)	0	4 (3)	118 (81)	141 (97)
MBL*	42	34 (81)	5 (12)	9 (21)	8 (19)	28 (67)
KPC-2	4	1 (25)	0	0	3 (75)	4 (100)
No-carbapenemase	13	2 (15)	0	0	11 (85)	13 (100)
carbapenem susceptible	50	1 (2)	0	0	49 (98)	50 (100)
Total	254	65 (26)	5 (2)	13 (5)	189 (74)	236 (93)

S: susceptible; I: intermediate; R: resistant; MBL: metallo-beta-lactamase; CRK: carbapenem resistant Klebsiella spp.

*31 of 42 MBL producing isolates also produce an OXA-48-like carbapenemase.

Table 4. ESBL type according to cefiderocol susceptibility as per EUCAST.

	Total (n = 254)			OXA48 (n = 145)			MBL (n = 42)			KPC (n = 4)			No-carbapenemase producer (n = 13)			Carbapenem susceptible (n = 50)
ESBL type, n (%)	CDRO R (n = 65)	CDRO S (n = 189)	p	CDRO R (n = 27)	CDRO S (n = 118)	p	CDRO R (n = 34)	CDRO S (n = 8)	p	CDRO R (n = 1)	CDRO S (n = 3)	p	CDRO R (n = 2)	CDRO S (n = 11)	p	CDRO R (n = 1)	CDRO S (n = 49)	p
CTX-M	61 (94)	135 (71)	0.000	27 (100)	94 (80)	0.01	31 (91)	6 (75)	0.2	0 (0)	3 (100)	0.05	2 (100)	8 (72)	0.4	1 (100)	24 (49)	0.31
SHV	65 (100)	167 (88)	0.004	27 (100)	108 (92)	0.12	34 (100)	6 (75)	0.003	1 (100)	3 (100)	NA	2 (100)	10 (91)	0.66	1 (100)	40 (82)	0.64
TEM	38 (58)	71 (38)	0.003	17 (63)	66 (56)	0.51	20 (59)	3 (38)	0.28	1 (100)	3 (100)	NA	1 (50)	1 (9)	0.14	0 (0)	1 (2)	0.88

CDRO: cefiderocol; S: susceptible; R: resistant

Data availability statement

The genomic dataset generated during this study is available in the public database [i.e. US National Library of Medicine (NLM) National Centre for Biotechnology Information (NCBI), PRJNA789336].