. 2022 Apr 18;28(4):398–407. doi: 10.1089/mdr.2021.0180

Table 4.

Pre- and Post-Cefiderocol MIC Changes, Resistance Criteria, Identified β-Lactamases, and Post-Treatment Whole-Genome Sequencing-Identified Mutations in Multilocus Sequence Typing-Confirmed Isogenic Isolates with a ≥ 4-Fold Post-Treatment Increase in MIC: Data from CREDIBLE-CR

				Cefiderocol MIC retests				Resistance according to established criteria, based on median MIC
Species and site of infection	Time point for MIC increase	Original MIC (μg/mL)	Fold of baseline MIC	MIC #2 (μg/mL)	MIC #3 (μg/mL)	Median MIC (μg/mL)	Fold of median baseline MIC	CLSI S/I/R ≤4/8/≥16	FDA S/I/R ≤4/8/≥16 ENT & ≤1/2/≥4 NF	EUCAST S/R ≤2/>2 (ENT, PA)	fT >4 × MIC (%)	C_min (μg/mL)	β-Lactamase identified at baseline and post-treatment (WGS)	Post-treatment mutation identified (WGS)
*Acinetobacter baumannii* Lung (VAP)	Baseline	0.25		1	1	1		S	S	S	NA	NA	ADC-25-like^d; OXA-23; OXA-66^d; TEM-1D
	Day 14	4	16 ×	2	4	4	4 ×	S	R	R			ADC-25-like^d; OXA-23; OXA-66^d; TEM-1D	PBP3 (H370Y)
*A. baumannii* Lung (VAP)	Baseline	1		1	2	1		S	S	S	100	26.4	ADC-25-like^d; OXA-23; OXA-69^d
	EOT	8	8 ×	64	64	64	64 ×	R	R	R			ADC-25-like^d; OXA-23-like; OXA-69^d	OXA-23 (N85I and P225S)
A. baumannii Lung (VAP)^a	Baseline	1		0.25	1	1		S	S	S	100	26.7	ADC-25-like^d; OXA-23; OXA-71^d
	Unscheduled (Day 10)	8	8 ×	8	8	8	8 ×	I	R	R			ADC-25-like^d; OXA-23; OXA-71^d	Not identified
K. pneumoniae Lung (VAP)	Baseline	0.06		≤0.03	0.06	0.06		S	S	S	100	8.24	SHV-61-like^e
	Unscheduled (Day 8)	0.5	8 ×	1	1	1	16 ×	S	S	S			SHV-61-like^e partial CDS; TEM-18	Not identified
K. pneumoniae Lung (HAP)^b	Baseline	0.25		0.12	0.25	0.25		S	S	S	NA	NA	KPC-2; SHV-1
	Day 14	2	8 ×	4	2	2	8 ×	S	S	S			KPC-2; SHV-1	Not identified
Pseudomonas aeruginosa Urine (cUTI)	Baseline	0.12		0.12	0.12	0.12		S	S	S	100	7.3	OXA-847^f; PDC-11; VIM-2
	EA	16	128 ×	16	16	16	128 ×	R	R	R			OXA-847^f; PDC-11; VIM-2	Not identified
*P. aeruginosa* Lung (HAP)	EA	0.25		0.12	0.12	0.12		S	S	S	NA	NA	OXA-488^f; PDC-30
	EOT	2	8 ×	2	2	2	16 ×	S	I	S			OXA-488^f; PDC-30-like	PDC30 (4 AA deletion “TPMA” position 316–319)
P. aeruginosa Lung (VAP)	Baseline	0.5		1	0.25	0.5		S	S	S	100	15.2	OXA-50-like^g; PDC-11
	EOT	2	4 ×	4	2	2	4 ×	S	I	S			OXA-50-like^g; PDC-11	Not identified
Stenotrophomonas maltophilia Lung (VAP)^c	Baseline	0.06		0.06	0.12	0.06		NA	NA	NA	100	51.7	L1, L2^h
	EOT	0.25	4 ×	0.12	0.25	0.25	4 ×	NA	NA	NA			L1, L2^h	Not identified

Bold text refers to isolates with mutations.

^{^a}

Treatment with combination of cefiderocol+ampicillin-sulbactam.

^{^b}

Treatment with combination of cefiderocol+tigecycline.

^{^c}

Treatment with combination of cefiderocol+levofloxacin.

^{^d}

In A. baumannii, OXA-66, OXA-69, OXA-71, and ADC-25 are naturally occurring and weakly expressed.

^{^e}

In K. pneumoniae, SHV-61 is naturally occurring.

^{^f}

In P. aeruginosa, OXA-847 and OXA-488 are naturally occurring and weakly expressed, and do not interfere with common resistance patterns. They belong to OXA-50-like group of β-lactamases.

^{^g}

OXA-50–like groups of β-lactamases are naturally occurring enzymes and weakly expressed.

^{^h}

L1 and L2 are naturally occurring β-lactamases; L1: a metallo-β-lactamase and L2: an extended-spectrum β-lactamase, respectively. L1 was not available in the ResFinder database but was detected by manual analysis of the assembled sequence.

CDS, coding sequences; cUTI, complicated urinary tract infection; NT, not tested.