Antimicrobial Activity of High-Proportion Cefepime-Tazobactam (WCK 4282) against a Large Number of Gram-Negative Isolates Collected Worldwide in 2014

Helio S. Sader; Mariana Castanheira; Rodrigo E. Mendes; Robert K. Flamm; Ronald N. Jones

doi:10.1128/AAC.02409-16

DOI: 10.1128/AAC.02409-16

Article Figures & Data

Tables

TABLE 1

Cumulative frequency distributions of cefepime and cefepime-tazobactam (with tazobactam at fixed concentration of 8 μg/ml) MIC results when tested against bacterial isolates^a

Organism (no. of isolates) and antimicrobial	No. of organisms (cumulative % inhibited) at MIC (μg/ml) of:
Organism (no. of isolates) and antimicrobial	≤0.03	0.06	0.12	0.25	0.5	1	2	4	8	16	32	64	>64
Enterobacteriaceae (6,219)
Cefepime	2,625 (42.2)	1,469 (65.8)	519 (74.2)	244 (78.1)	155 (80.6)	93 (82.1)	122 (84.0)	92 (85.5)	147 (87.9)	151 (90.3)	131 (92.4)	166 (95.1)	305 (100.0)
Cefepime-tazobactam	3,175 (51.1)	1,585 (76.5)	596 (86.1)	304 (91.0)	141 (93.3)	84 (94.6)	68 (95.7)	40 (96.4)	36 (96.9)	42 (97.6)	26 (98.0)	54 (98.9)	68 (100.0)
E. coli (2,211)
Cefepime	1,000 (45.2)	535 (69.4)	162 (76.8)	48 (78.9)	38 (80.6)	20 (81.5)	44 (83.5)	37 (85.2)	67 (88.2)	65 (91.2)	52 (93.5)	58 (96.2)	85 (100.0)
Cefepime-tazobactam	1,290 (58.3)	551 (83.3)	207 (92.6)	93 (96.8)	27 (98.1)	10 (98.5)	14 (99.1)	7 (99.5)	6 (99.7)	3 (99.9)	1 (99.9)	0 (>99.9)	2 (100.0)
E. coli with ESBL phenotype (471)
Cefepime	5 (1.1)	14 (4.0)	18 (7.9)	10 (10.0)	18 (13.8)	12 (16.3)	33 (23.4)	35 (30.8)	66 (44.8)	65 (58.6)	52 (69.6)	58 (82.0)	85 (100.0)
Cefepime-tazobactam	87 (18.5)	148 (49.9)	112 (73.7)	65 (87.5)	22 (92.1)	5 (93.2)	14 (96.2)	6 (97.5)	6 (98.7)	3 (99.4)	1 (99.6)	0 (99.6)	2 (100.0)
Klebsiella spp. (2,138)
Cefepime	981 (45.9)	343 (61.9)	113 (67.2)	60 (70.0)	39 (71.8)	32 (73.3)	31 (74.8)	27 (76.1)	61 (78.9)	73 (82.3)	72 (85.7)	97 (90.2)	209 (100.0)
Cefepime-tazobactam	1,139 (53.3)	410 (72.5)	142 (79.1)	87 (83.2)	58 (85.9)	40 (87.7)	34 (89.3)	29 (90.7)	25 (91.9)	36 (93.5)	22 (94.6)	52 (97.0)	64 (100.0)
Klebsiella spp. with ESBL phenotype (661)
Cefepime	2 (0.3)	7 (1.4)	12 (3.2)	16 (5.6)	26 (9.5)	28 (13.8)	31 (18.5)	27 (22.5)	61 (31.8)	73 (42.8)	72 (53.7)	97 (68.4)	209 (100.0)
Cefepime-tazobactam	103 (15.6)	103 (31.2)	58 (39.9)	53 (48.0)	46 (54.9)	36 (60.4)	34 (65.5)	29 (69.9)	25 (73.7)	36 (79.1)	22 (82.5)	52 (90.3)	64 (100.0)
K. pneumoniae (1,788)
Cefepime	747 (41.8)	293 (58.2)	96 (63.5)	50 (66.3)	32 (68.1)	23 (69.4)	23 (70.7)	23 (72.0)	57 (75.2)	70 (79.1)	70 (83.0)	95 (88.3)	209 (100.0)
Cefepime-tazobactam	879 (49.2)	372 (70.0)	129 (77.2)	78 (81.5)	51 (84.4)	31 (86.1)	28 (87.7)	26 (89.1)	21 (90.3)	36 (92.3)	21 (93.5)	52 (96.4)	64 (100.0)
K. pneumoniae with ESBL phenotype (602)
Cefepime	1 (0.2)	3 (0.7)	5 (1.5)	8 (2.8)	19 (6.0)	19 (9.1)	23 (13.0)	23 (16.8)	57 (26.2)	70 (37.9)	70 (49.5)	95 (65.3)	209 (100.0)
Cefepime-tazobactam	92 (15.3)	96 (31.2)	53 (40.0)	47 (47.8)	39 (54.3)	27 (58.8)	28 (63.5)	26 (67.8)	21 (71.3)	36 (77.2)	21 (80.7)	52 (89.4)	64 (100.0)
MEM-nonsusceptible K. pneumoniae (183)
Cefepime								1 (0.5)	6 (3.8)	6 (7.1)	17 (16.4)	33 (34.4)	120 (100.0)
Cefepime-tazobactam							6 (3.3)	10 (8.7)	12 (15.3)	32 (32.8)	16 (41.5)	49 (68.3)	58 (100.0)
Klebsiella oxytoca (345)
Cefepime	230 (66.7)	50 (81.2)	16 (85.8)	10 (88.7)	7 (90.7)	9 (93.3)	8 (95.7)	4 (96.8)	4 (98.0)	3 (98.8)	2 (99.4)	2 (100.0)
Cefepime-tazobactam	256 (74.2)	38 (85.2)	12 (88.7)	9 (91.3)	7 (93.3)	9 (95.9)	6 (97.7)	3 (98.6)	4 (99.7)	0 (99.7)	1 (100.0)
Klebsiella oxytoca with ESBL phenotype (59)
Cefepime	1 (1.7)	4 (8.5)	7 (20.3)	8 (33.9)	7 (45.8)	9 (61.0)	8 (74.6)	4 (81.4)	4 (88.1)	3 (93.2)	2 (96.6)	2 (100.0)
Cefepime-tazobactam	11 (18.6)	7 (30.5)	5 (39.0)	6 (49.2)	7 (61.0)	9 (76.3)	6 (86.4)	3 (91.5)	4 (98.3)	0 (98.3)	1 (100.0)
P. mirabilis (228)
Cefepime	27 (11.8)	144 (75.0)	32 (89.0)	8 (92.5)	1 (93.0)	7 (96.1)	1 (96.5)	1 (96.9)	3 (98.2)	0 (98.2)	0 (98.2)	1 (98.7)	3 (100.0)
Cefepime-tazobactam	39 (17.1)	155 (85.1)	29 (97.8)	4 (99.6)	1 (100.0)
P. mirabilis with ESBL phenotype (19)
Cefepime				2 (10.5)	1 (15.8)	7 (52.6)	1 (57.9)	1 (63.2)	3 (78.9)	0 (78.9)	0 (78.9)	1 (84.2)	3 (100.0)
Cefepime-tazobactam		4 (21.1)	10 (73.7)	4 (94.7)	1 (100.0)
Enterobacter spp. (629)
Cefepime	208 (33.1)	151 (57.1)	78 (69.5)	55 (78.2)	39 (84.4)	15 (86.8)	30 (91.6)	19 (94.6)	11 (96.3)	9 (97.8)	4 (98.4)	5 (99.2)	5 (100.0)
Cefepime-tazobactam	233 (37.0)	151 (61.0)	92 (75.7)	63 (85.7)	38 (91.7)	25 (95.7)	13 (97.8)	4 (98.4)	3 (98.9)	3 (99.4)	2 (99.7)	1 (99.8)	1 (100.0)
CAZ-nonsusceptible Enterobacter spp. (179)
Cefepime		4 (2.2)	17 (11.7)	33 (30.2)	31 (47.5)	15 (55.9)	28 (71.5)	18 (81.6)	10 (87.2)	9 (92.2)	4 (94.4)	5 (97.2)	5 (100.0)
Cefepime-tazobactam	1 (0.6)	11 (6.7)	41 (29.6)	45 (54.7)	32 (72.6)	23 (85.5)	12 (92.2)	4 (94.4)	3 (96.1)	3 (97.8)	2 (98.9)	1 (99.4)	1 (100.0)
Morganella morganii (165)
Cefepime	104 (63.0)	47 (91.5)	6 (95.2)	4 (97.6)	1 (98.2)	0 (98.2)	1 (98.8)	2 (100.0)
Cefepime-tazobactam	129 (78.2)	30 (96.4)	3 (98.2)	3 (100.0)
Citrobacter spp. (311)
Cefepime	197 (63.3)	45 (77.8)	12 (81.7)	14 (86.2)	15 (91.0)	10 (94.2)	6 (96.1)	4 (97.4)	1 (97.7)	1 (98.1)	2 (98.7)	3 (99.7)	1 (100.0)
Cefepime-tazobactam	200 (64.3)	57 (82.6)	18 (88.4)	19 (94.5)	7 (96.8)	5 (98.4)	3 (99.4)	0 (99.4)	1 (99.7)	0 (99.7)	0 (99.7)	1 (100.0)
Serratia marcescens (245)
Cefepime	8 (3.3)	98 (43.3)	81 (76.3)	31 (89.0)	11 (93.5)	4 (95.1)	4 (96.7)	1 (97.1)	3 (98.4)	2 (99.2)	0 (99.2)	1 (99.6)	1 (100.0)
Cefepime-tazobactam	8 (3.3)	116 (50.6)	72 (80.0)	33 (93.5)	10 (97.6)	2 (98.4)	3 (99.6)	0 (99.6)	1 (100.0)
Proteus vulgaris (144)
Cefepime	11 (7.6)	76 (60.4)	31 (81.9)	15 (92.4)	6 (96.5)	1 (97.2)	3 (99.3)	1 (100.0)
Cefepime-tazobactam	32 (22.2)	84 (80.6)	26 (98.6)	2 (100.0)
Providencia spp. (148)
Cefepime	89 (60.1)	30 (80.4)	4 (83.1)	9 (89.2)	5 (92.6)	4 (95.3)	2 (96.6)	0 (96.6)	1 (97.3)	1 (98.0)	1 (98.6)	1 (99.3)	1 (100.0)
Cefepime-tazobactam	105 (70.9)	31 (91.9)	7 (96.6)	0 (96.6)	0 (96.6)	2 (98.0)	1 (98.6)	0 (98.6)	0 (98.6)	0 (98.6)	1 (99.3)	0 (99.3)	1 (100.0)
P. aeruginosa (1,171)
Cefepime			4 (0.3)	4 (0.7)	36 (3.8)	136 (15.4)	414 (50.7)	184 (66.4)	169 (80.9)	110 (90.3)	63 (95.6)	24 (97.7)	27 (100.0)
Cefepime-tazobactam		1 (0.1)	5 (0.5)	6 (1.0)	17 (2.5)	171 (17.1)	404 (51.6)	184 (67.3)	177 (82.4)	108 (91.6)	61 (96.8)	15 (98.1)	22 (100.0)
CAZ-nonsusceptible P. aeruginosa (252)
Cefepime						1 (0.4)	3 (1.6)	17 (8.3)	40 (24.2)	79 (55.6)	61 (79.8)	24 (89.3)	27 (100.0)
Cefepime-tazobactam						2 (0.8)	4 (2.4)	24 (11.9)	45 (29.8)	82 (62.3)	58 (85.3)	15 (91.3)	22 (100.0)
MEM-nonsusceptible P. aeruginosa (244)
Cefepime						1 (0.4)	15 (6.6)	23 (16.0)	52 (37.3)	62 (62.7)	45 (81.1)	20 (89.3)	26 (100.0)
Cefepime-tazobactam						4 (1.6)	13 (7.0)	26 (17.6)	56 (40.6)	65 (67.2)	46 (86.1)	14 (91.8)	20 (100.0)
A. baumannii (591)
Cefepime				1 (0.2)	5 (1.0)	8 (2.4)	42 (9.5)	54 (18.6)	25 (22.8)	21 (26.4)	42 (33.5)	105 (51.3)	288 (100.0)
Cefepime-tazobactam	53 (9.0)	17 (11.8)	11 (13.7)	14 (16.1)	9 (17.6)	15 (20.1)	18 (23.2)	8 (24.5)	9 (26.1)	31 (31.3)	55 (40.6)	90 (55.8)	261 (100.0)

↵a Tazobactam was used at a fixed concentration of 8 μg/ml, and the results are for 7,981 bacterial isolates from all geographic regions combined. Values in bold indicate MIC₅₀s and MIC₉₀s. Abbreviations: ESBL phenotype, extended-spectrum β-lactamase (ESBL)-screen-positive phenotype, defined as an MIC of ≥2 μg/ml for ceftriaxone, ceftazidime, and/or aztreonam; CAZ nonsusceptible, ceftazidime nonsusceptible (MICs, ≥8 μg/ml for Enterobacteriaceae and ≥16 μg/ml for P. aeruginosa); MEM nonsusceptible, meropenem nonsusceptible (MICs, ≥2 μg/ml for Enterobacteriaceae and ≥4 μg/ml for P. aeruginosa) (7).

TABLE 2

Activity of cefepime-tazobactam combination and comparator agents tested against bacterial isolates collected worldwide in 2014

Organism and antimicrobial agent	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	% susceptible by use of CLSI/EUCAST breakpoint criteria^a (no. of isolates)
Organism and antimicrobial agent	MIC₅₀ (μg/ml)	MIC₉₀ (μg/ml)	United States	Europe	Latin America	APAC^d	China	All regions
Enterobacteriaceae			(2,466)	(2,351)	(466)	(693)	(243)	(6,219)
Cefepime-tazobactam (tazobactam at fixed 8 μg/ml)	≤0.03	0.25	98.3/97.6^b	95.8/94.3^b	94.4/91.4^b	98.7/97.8^b	93.8/92.6^b	96.9/95.7^b
Cefepime-tazobactam (tazobactam at fixed 4 μg/ml)	0.06	0.5	98.1/97.1^b	94.7/93.2^b	92.9/90.3^b	98.1/96.5^b	93.4/91.8^b	96.2/94.9^b
Cefepime	0.06	16	92.2/90.4	81.1/79.2	64.8/63.3	86.3/83.8	60.5/56.4	84.0/82.1
Ceftazidime	0.25	>16	88.9/86.4	78.4/74.6	65.9/60.3	82.5/78.2	68.7/58.8	81.7/78.0
Ceftriaxone	≤0.06	>8	84.5/84.5	72.1/72.1	58.4/58.4	77.3/77.3	49.0/49.0	75.7/78.0
Piperacillin-tazobactam	2	32	92.0/88.9	84.2/79.5	82.6/78.8	89.2/85.0	84.6/79.3	87.7/83.8
Meropenem	0.03	0.06	97.9/98.2	95.5/95.9	94.8/95.5	98.6/98.7	94.2/94.2	96.7/97.0
Levofloxacin	≤0.12	>8	84.4/83.1	78.0/75.9	63.5/62.7	82.7/81.1	63.2/61.2	79.4/77.8
Gentamicin	≤1	4	90.1/88.4	85.3/84.1	72.7/71.9	84.6/84.3	63.0/62.6	85.3/84.1
P. aeruginosa			(390)	(391)	(109)	(197)	(84)	(1,171)
Cefepime-tazobactam (tazobactam at fixed 8 μg/ml)	2	16	85.9^c	79.8^c	79.8^c	85.8^c	73.8^c	82.4^b
Cefepime-tazobactam (tazobactam at fixed 4 μg/ml)	2	16	86.2^c	78.5^c	78.9^c	85.8^c	73.8^c	82.0^b
Cefepime	2	16	84.4/84.4	78.3/78.3	77.1/77.1	84.8/84.8	72.6/72.6	80.9/80.9
Ceftazidime	2	>16	87.2/87.2	73.1/73.1	70.6/70.6	79.7/79.7	70.2/70.2	78.5/78.5
Piperacillin-tazobactam	4	>64	86.2/86.2	74.7/74.7	76.1/76.1	81.7/81.7	66.7/66.7	79.2/79.2
Meropenem	0.5	8	85.6/85.6	73.9/73.9	75.2/75.2	83.2/53.2	69.0/69.0	79.2/79.2
Levofloxacin	0.5	>4	79.0/67.7	71.1/63.7	67.0/59.6	80.7/72.6	76.2/67.9	75.3/66.4
Amikacin	2	8	97.2/92.8	91.0/86.7	90.8/89.9	94.4/91.9	91.7/88.1	93.7/90.0
Acinetobacter spp.			(152)	(184)	(72)	(93)	(90)	(591)
Cefepime-tazobactam (tazobactam at fixed 8 μg/ml)	64	>64	53.9^c	18.5^c	9.7^c	18.3^c	15.6^c	26.1^b
Cefepime-tazobactam (tazobactam at fixed 4 μg/ml)	64	>64	53.3^c	17.4^c	8.3^c	18.3^c	15.6^c	25.9^b
Cefepime	64	>64	46.7/—	16.3/—	6.9/—	17.2/—	14.4/—	22.8/—
Ceftazidime	>32	>32	54.6/—	17.4/—	9.7/—	19.4/—	14.4/—	25.9/—
Piperacillin-tazobactam	>64	>64	53.9/—	19.6/—	6.9/—	17.2/—	12.4/—	25.4/—
Ampicillin-sulbactam	32	>32	63.6/—	24.5/—	18.1/—	16.1/—	15.6/—	31.0/—
Meropenem	>32	>32	56.6/56.6	26.1/26.1	11.1/11.1	17.2/17.2	16.7/16.7	29.3/—
Levofloxacin	>4	>4	53.3/52.6	18.5/17.4	11.1/11.1	18.3/18.3	15.6/15.6	26.1/25.4
Amikacin	>32	>32	78.1/74.8	28.8/26.6	13.9/12.5	30.1/26.9	21.1/18.9	38.6/36.1

↵a Unless indicated otherwise, the data are based on the criteria published by CLSI (7) and EUCAST (12). For cefepime-tazobactam, only CLSI criteria were applied. — indicates that breakpoints have not been established.
↵b Percentage inhibited by ≤8 μg/ml cefepime/≤2 μg/ml cefepime, according to the CLSI breakpoint criteria for cefepime susceptibility for high and low dosages (2 g every 8 h and 1 g every 12 h, respectively), as published in CLSI document M100-S26 (7).
↵c Percentage inhibited at ≤8 μg/ml, according to the CLSI breakpoint for cefepime susceptibility published by the CLSI (7) and EUCAST (12) (P. aeruginosa only).
↵d APAC, Asia-Pacific region excluding China.

TABLE 3

Summary of activity of cefepime-tazobactam with tazobactam at fixed 8 μg/ml stratified by geographic region

Organisms (no. of isolates for all regions combined)^b	MIC₅₀/MIC₉₀ (μg/ml) of cefepime-tazobactam with tazobactam at fixed 8 μg/ml (% isolates inhibited at ≤8 µg/ml)^a
Organisms (no. of isolates for all regions combined)^b	United States	Europe	Latin America	APAC^b	China	All regions
Enterobacteriaceae (6,219)	≤0.03/0.25 (98.3)	≤0.03/0.5 (95.8)	0.06/1 (94.4)	≤0.03/0.25 (98.7)	0.06/0.5 (93.8)	≤0.03/0.25 (96.9)
E. coli (2,211)	≤0.03/0.12 (99.9)	≤0.03/0.12 (100.0)	0.06/0.25 (100.0)	≤0.03/0.06 (99.7)	0.06/0.25 (96.2)	≤0.03/0.12 (99.7)
ESBL phenotype (471)	0.12/0.25 (99.0)	0.12/1 (100.0)	0.12/0.25 (100.0)	0.06/0.25 (98.4)	0.06/0.25 (94.2)	0.12/0.5 (98.7)
Klebsiella spp. (2,138)	≤0.03/0.25 (95.9)	0.06/32 (87.4)	0.06/64 (85.0)	≤0.03/0.25 (96.5)	0.06/64 (86.1)	≤00.03/4 (91.9)
ESBL phenotype (661)	0.5/32 (78.8)	0.5/>64 (71.8)	1/>64 (72.2)	0.12/64 (87.9)	0.12/64 (66.7)	0.5/64 (73.7)
K. pneumoniae (1,788)	≤0.03/0.25 (94.9)	0.06/64 (85.0)	0.06/64 (83.3)	≤0.03/0.5 (96.2)	0.06/64 (85.1)	0.06/8 (90.3)
MEM-non-susceptible (183)	16/>64 (20.0)	64/>64 (14.6)	64/>64 (20.8)	>64/— (0.0)	64/>64 (0.0)	64/>64 (15.3)
Klebsiella oxytoca (345)	≤0.03/0.12 (100.0)	≤0.03/1 (99.2)	≤0.03/1 (100.0)	≤0.03/0.12 (100.0)	≤0.03/— (100.0)	≤0.03/0.25 (99.7)
ESBL-phenotype (59)	0.5/4 (100.0)	1/8 (96.4)	1/— (100.0)	0.12/— (100.0)		0.5/4 (98.3)
P. mirabilis (228)	0.06/0.12 (100.0)	0.06/0.12 (100.0)	0.06/0.12 (100.0)	0.06/0.06 (100.0)	0.06/— (100.0)	0.06/0.12 (100.0)
ESBL phenotype (19)	0.12/— (100.0)	0.12/0.25 (100.0)	0.25 (100.0)		0.06/— (100.0)	0.12/0.25 (100.0)
Enterobacter spp. (629)	0.06/0.25 (99.2)	0.06/0.5 (98.7)	0.06/1 (98.2)	0.06/1 (100.0)	0.06/1 (97.4)	0.06/0.5 (98.9)
CAZ nonsusceptible (179)	0.25/2 (96.2)	0.25/2 (95.5)	0.25/2 (95.2)	0.25/2 (100.0)	0.25/8 (93.3)	0.25/2 (96.1)
Morganella morganii (165)	≤0.03/0.06 (100.0)	≤0.03/0.06 (100.0)	≤0.03/— (100.0)	≤0.03/≤0.03 (100.0)	≤0.03/— (100.0)	≤0.03/0.06 (100.0)
Citrobacter spp. (311)	≤0.03/0.12 (100.0)	≤0.03/0.25 (99.2)	0.06/— (100.0)	≤0.03/0.25 (100.0)	0.12/— (100.0)	≤0.03/0.25 (99.7)
Serratia marcescens (245)	0.06/0.25 (100.0)	0.06/0.25 (100.0)	0.06/0.12 (100.0)	0.06/0.12 (100.0)	0.06/0.25 (100.0)	0.06/0.25 (100.0)
Proteus vulgaris (144)	0.06/0.12 (100.0)	0.06/0.12 (100.0)	≤0.03/— (100.0)	0.06/— (100.0)	0.06/— (100.0)	0.06/0.12 (100.0)
Providencia spp. (148)	≤0.03/0.12 (98.9)	≤0.03/0.06 (98.1)	≤0.03/— (100.0)	≤0.03/— (100.0)		≤0.03/0.06 (98.6)
P. aeruginosa (1,171)	2/16 (85.9)	4/16 (79.8)	4/32 (79.8)	2/16 (85.8)	4/32 (73.8)	2/16 (82.4)
CAZ nonsusceptible (252)	16/64 (22.0)	16/32 (31.4)	16/>64 (37.5)	16/>64 (35.0)	32/>64 (20.0)	16/64 (29.8)
MEM nonsusceptible (244)	16/64 (37.5)	16/32 (42.2)	16/>64 (44.4)	16/>64 (39.4)	32/>64 (15.6)	16/64 (40.6)
A. baumannii (591)	4/>64 (53.9)	64/>64 (18.5)	>64/>64 (9.7)	>64/>64 (18.3)	>64/>64 (15.6)	64/>64 (26.1)

↵a According to the breakpoint for cefepime susceptibility for a high dosage (2 g every 8 h) published in CLSI document M100-S26 (7). —, there were too few isolates (<10) with which to calculate the MIC₉₀.
↵b Abbreviations: APAC, Asia-Pacific region excluding China; ESBL phenotype, extended-spectrum β-lactamase (ESBL)-screen-positive phenotype, defined as an MIC of ≥2 μg/ml for ceftriaxone, ceftazidime, and/or aztreonam; CAZ nonsusceptible, ceftazidime nonsusceptible (MICs, ≥8 μg/ml for Enterobacteriaceae and ≥16 μg/ml for P. aeruginosa); MEM nonsusceptible, meropenem nonsusceptible (MICs, ≥2 μg/ml for Enterobacteriaceae and ≥4 μg/ml for P. aeruginosa) (7).

TABLE 4

Regional occurrence of resistance phenotypes^a

Geographic region	% of isolates
	ESBL phenotype				MEM-NS		CAZ-NS
	E. coli	K. pneumoniae	K. oxytoca	P. mirabilis	K. pneumoniae	P. aeruginosa	Enterobacter spp.	P. aeruginosa
United States	14.4	16.2	12.9	1.1	6.0	26.1	22.2	26.9
Europe	19.3	49.3	22.6	14.9	15.7	14.4	28.9	12.8
Latin American	37.4	58.0	18.8	13.3	16.0	24.8	39.3	29.4
APAC	18.8	29.3	22.7	0.0	3.8	16.8	33.8	20.3
China	66.3	44.8	0.0	20.0	14.9	31.0	39.5	29.8
All regions combined	21.3	33.7	17.1	8.3	10.2	20.8	28.5	21.5

↵a Abbreviations: ESBL phenotype, extended-spectrum β-lactamase (ESBL)-screen-positive phenotype, defined as an MIC of ≥2 μg/ml for ceftriaxone, ceftazidime, and/or aztreonam (20); MEM-NS, meropenem nonsusceptible (MICs, ≥2 μg/ml for K. pneumoniae and ≥4 μg/ml for P. aeruginosa) (7); CAZ-NS, ceftazidime nonsusceptible (MICs, ≥8 μg/ml for Enterobacter spp. and ≥16 μg/ml for P. aeruginosa) (7); APAC, Asia-West Pacific region excluding China.