In vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, and other comparable agents against clinically important Gram-negative bacilli: results from the 2017 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

Figures & data

Table 1 In vitro susceptibilities (evaluated based on the criteria of the Clinical and Laboratory Standards Institute 2018 and European Committee on Antimicrobial Susceptibility Testing 2018^a) of bloodstream isolates of Escherichia coli, Klebsiella pneumoniae, and other Gram-negative bacteria, including isolates of non-typhoid Salmonella species from any site, fecal Shigella species, and Neisseria gonorrhoeae from the genitourinary system, collected from patients treated at 16 major teaching hospitals across Taiwan in 2017 to key antimicrobial agents tested

Bacterial species (isolate no.) and antimicrobial agent tested	MIC (mg/L)			% of indicated susceptibility
	Range	MIC50	MIC90	S	I	R
Escherichia coli (686)
Ceftolozane-tazobactam	0.12->64	0.25	1	94.3	2.2	3.5
Ceftazidime-avibactam	≤0.06->64	0.12	0.25	99.9^a	NA	0.l^a
Ceftazidime	≤0.12->256	0.25	32	74.5	5.1	20.4
Cefepime	≤0.12->64	≤0.12	64	78.0	7.0	l5.0
Ertapenem	≤0.06->64	≤0.06	0.12	98.0	0.7	l.3
Ciprofloxacin	≤0.06->64	0.25	64	68.2/59.9^a	l.3/6.7^a	30.5/33.4^a
Levofloxacin	≤0.06->64	0.25	16	69.2/63.8^a	0.6/4.4^a	30.2/3l.8^a
Colistin	≤0.12-8	0.25	0.25	98.8	NA	l.2
Klebsiella pneumoniae (673)
Ceftolozane-tazobactam	≤0.06->64	0.5	64	84.l/80.7^a	1.2/NA	l4.7/l9.l^a
Ceftazidime-avibactam	≤0.06->64	0.12	1	99.1^a	NA	0.9^a
Ceftazidime	≤0.12->256	0.25	256	73.7	3.4	22.9
Cefepime	≤0.12->64	≤0.12	32	82.8	2.5	l4.7
Ertapenem	≤0.06->64	≤0.06	1	89.5	3.6	7.0
Meropenem	≤0.06->64	≤0.06	0.12	94.5	0.6	4.9
Ciprofloxacin	≤0.06->64	≤0.06	64	79.5/66.4^a	l.8/6.7^a	l8.7/26.9^a
Levofloxacin	≤0.06->64	≤0.06	32	8l.0/69.7^a	2.2/9.5^a	l6.8/20.8^a
Colistin	≤0.12->64	0.25	0.5	97.6	NA	2.4
Non-typhoid Salmonella spp. (221)
Ampicillin	0.5->64	4	>64	51.6	1.8	46.6
Cefixime	≤0.12->64	≤0.12	>64	87.3	0.5	l2.2
Ceftriaxone	≤0.12-64	≤0.12	1	92.3	1.8	5.9
Ertapenem	≤0.06-0.25	≤0.06	≤0.06	100	0	0
Ciprofloxacin	≤0.06-16	≤0.06	0.5	78.7/78.7^a	l8.l/NA^a	3.2/2l.3^a
Levofloxacin	≤0.06-16	≤0.06	1	78.7/89.6^a	l0.9/8.6^a	l0.4/l.8^a
Moxifloxacin	≤0.06-16	0.12	2	79.2^a	NA^a	20.8^a
Gentamicin	≤0.12->64	0.5	1	96.4	0.5	3.2
Trimethoprim-sulfamethoxazole	≤0.12->32	≤0.12	>32	74.2	NA	25.8
Colistin	0.25-16	2	4	53.8	na	46.2
Shigella spp. (21)
Ampicillin	1->64	>64	>64	38.1	0	6l.9
Ceftriaxone	≤0.12	≤0.12	≤0.12	100	0	0
Ertapenem	≤0.06	≤0.06	≤0.06	100	0	0
Ciprofloxacin	≤0.06-16	≤0.06	16	61.9	0	38.l
Levofloxacin	≤0.06-8	≤0.06	8	61.9	l9.0	l9.0
Trimethoprim-sulfamethoxazole	≤0.12->32	1	>32	61.9	na	38.l
Azithromycin-Shige//a flexneri (17)	1->64	4	>64	70.6	na	29.4
Azithromycin-Shigella sonnei (4)	8-128	8	128	75	na	25
N. gonorrhoeae (129)
Cefotaxime	≤0.03-0.5	0.06	0.25	100/89.1^a	NA/NA^a	NA/l0.9^a
Cefixime	≤0.03-0.5	0.06	0.12	96.1/89.1^a	NA/NA^a	NA/l0.9^a
Cefpodoxime	≤0.03-2	0.25	0.5	89.9	na	na
Ciprofloxacin	≤0.008-128	4	16	2.3	0	97.7
Doxycycline	0.25-32	8	16	NA	na	na
Azithromycin	≤0.03->32	0.25	0.5	96.9/60.5^a	NA/3l.0^a	3.l/8.5^a

Note: ^aDenotes a significantly statistical difference (P<0.05) between different susceptibility subgroups.

Abbreviations: I, intermediate; MIC, minimum inhibitory concentration; NA, non-applicable; R, resistant; S, susceptible.

Figure 1 Comparison of (A) in vitro non-susceptibility to important antibiotics among overall, hospital-acquired, and community-acquired bloodstream Escherichia coli isolates, (B) Klebsiella pneumoniae isolates collected from 16 major teaching hospitals across Taiwan in 2017, and (C) in vitro non-susceptibility to important antibiotics between bloodstream Escherichia coli (n=148) and K. pneumoniae isolates (n=92) exhibiting the phenotype of extended-spectrum β-lactamase (unrelated to carbapenemase) production (ie, MDR phenotype).

Abbreviations: CAZ–AVB, ceftazidime–avibactam; CLSI, Clinical and Laboratory Standards Institute 2018; CLZ–TAZ, ceftolozane–tazobactam; EUCAST, European Committee on Antimicrobial Susceptibility Testing; MDR, multidrug resistance.

Table 2 MIC values of some key antibiotics against isolates of mcr-1-harboring Escherichia coli (n=5) and Klebsiella pneumoniae (n=4) collected from 16 major teaching hospitals throughout Taiwan in 2017

Bacterial species and isolates	MIC (mg/L)
	E. coli					K. pneumoniae
	1	2	3	4	5	1	2^a	3	4^b
Amoxicillin-clavulanate	32	8	8	64	8	32	128	64	i28
Cefoxitin	128	8	4	128	2	32	128	128	128
Ceftazidime	16	0.5	0.5	32	0.0625	1	512	512	512
Ceftriaxone	16	128	128	128	0.0625	0.25	128	16	128
Cefepime	0.25	4	4	8	0.0625	0.25	128	0.25	128
Piperacillin-tazobactam	4	2	2	8	2	256	256	256	256
C eftazidime-avibactam	0.12	0.12	0.03	0.25	0.03	0.50	4	2	128
Ceftolozane-tazobactam	1	0.25	0.25	2	0.50	1	64	32	128
Ertapenem	0.03	0.03	0.03	0.03	0.03	0.03	128	1	128
Imipenem	0.25	0.12	0.12	0.25	0.12	0.03	64	0.50	64
Meropenem	0.03	0.03	0.03	0.03	0.03	0.03	128	0.12	128
Ciprofloxacin	128	0.03	0.03	128	8	0.25	128	8	64
Amikacin	2	2	2	2	1	2	1	2	128
Tigecycline	0.25	0.50	0.25	0.50	0.25	1	2	1	0.50

Notes: ^aThis isolate also harbors bla_KPC- and bla_OXA-48-like alleles. ^bThis isolate also harbors the bla_KPC allele.

Abbreviation: MIC, minimum inhibitory concentration.

Figure 2 Comparison of in vitro non-susceptibility to important antibiotics of hospital-acquired Escherichia coli (n=106) and Klebsiella pneumoniae bloodstream isolates (n=212) collected from 16 major teaching hospitals across Taiwan in 2017.

Abbreviations: CAZ–AVB, ceftazidime–avibactam; CLSI, Clinical and Laboratory Standards Institute 2018; CLZ–TAZ, ceftolozane–tazobactam; EUCAST, European Committee on Antimicrobial Susceptibility Testing 2018.