Ceftazidime/Avibactam and Other Commonly Used Antibiotics Activity Against Enterobacterales and Pseudomonas aeruginosa Isolated in Poland in 2015–2019

Figures & data

Figure 1 Ceftazidime/avibactam MIC distribution for Enterobacterales (n=1523) by phenotype. The dashed line shows the breakpoint for ceftazidime/avibactam according to EUCAST (EUCAST Clinical Breakpoint Tables v. 11.0). 17 isolates with MIC above the breakpoint was observed, including 1 strain with MIC₉₀ = 64 µg/mL and 16 strains with MIC₉₀ = 256 µg/mL; all of them were MDR strains, including 16 ESBL producers and 12 CRE.

Table 1 In vitro Activity of Ceftazidime/Avibactam and Other Commonly Used Antibiotics Tested Against 1607 Enterobacterales Isolates Collected from 2015 to 2019

Antibacterial	n	% S	% I	MIC90	MIN (μg/mL)	MAX (μg/mL)
Enterobacterales (n=1607)
Amikacin	1607	94.2	n/a	8	0.25	128
Aztreonam	1523	62.4	2.5	128	0.015	256
Cefepime	1607	65.7	4.3	32	0.12	64
Ceftazidime	1607	62.5	3.7	128	0.015	256
Ceftazidime/avibactam	1523	98.9	n/a	0.5	0.015	256
Ceftolozane/tazobactam^a	401	87.5	n/a	4	0.06	64
Colistin^b	1294	97.0	n/a	1	0.06	16
Doripenem^c	853	97.5	1.1	0.25	0.008	16
Gentamicin^d	670	76.1	n/a	32	0.12	32
Imipenem^e	180	n/a	95.0	4	0.12	16
Imipenem^f	1343	96.7	1.2	1	0.06	16
Levofloxacin	1607	62.5	4.9	16	0.008	16
Meropenem	1607	96.5	2.0	0.12	0.008	32
Piperacillin/tazobactam	1607	70.9	n/a	128	0.12	256
Tigecycline^g	499	98.2	n/a	2	0.015	8
Enterobacterales MDR (n=691)
Amikacin	691	87.3	n/a	16	0.25	128
Aztreonam	674	16.6	4.0	256	0.015	256
Cefepime	691	23.9	8.7	64	0.12	64
Ceftazidime	691	17.2	5.6	256	0.015	256
Ceftazidime/avibactam	674	97.5	n/a	1	0.015	256
Ceftolozane/tazobactam^a	164	69.5	n/a	32	0.06	64
Colistin^b	626	94.1	n/a	1	0.06	16
Doripenem^c	340	94.7	2.1	0.5	0.008	16
Gentamicin^d	334	53.6	n/a	32	0.12	32
Imipenem^e	42	n/a	85.7	8	0.25	16
Imipenem^f	632	93.4	2.2	2	0.06	16
Levofloxacin	691	29.7	8.0	16	0.03	16
Meropenem	691	91.9	4.6	2	0.008	32
Piperacillin/tazobactam	691	34.4	n/a	256	0.12	256
Tigecycline^g	144	95.1	n/a	2	0.06	8
Enterobacterales ESBL (n=454)
Amikacin	454	86.8	n/a	16	0.25	128
Aztreonam	434	1.4	4.8	256	0.25	256
Cefepime	454	6.6	4.2	64	0.12	64
Ceftazidime	454	4.0	6.8	256	0.5	256
Ceftazidime/avibactam	434	96.3	n/a	1	0.03	256
Ceftolozane/tazobactam^a	99	66.7	n/a	64	0.12	64
Colistin^b	426	93.9	n/a	1	0.06	16
Doripenem^c	262	93.5	2.7	0.5	0.008	16
Gentamicin^d	172	45.4	n/a	32	0.12	32
Imipenem^e	7	n/a	85.7	16	1	16
Imipenem^f	427	91.1	3.0	2	0.06	16
Levofloxacin	454	17.8	9.9	16	0.03	16
Meropenem	454	89.7	6.0	4	0.015	32
Piperacillin/tazobactam	454	29.3	n/a	256	0.25	256
Tigecycline^g	83	95.2	n/a	64	1	64
Enterobacterales CRE (n=24)
Amikacin	24	62.5	n/a	128	0.5	128
Aztreonam	23	8.7	0	256	0.015	256
Cefepime	24	4.2	4.2	64	0.5	64
Ceftazidime	24	4.2	0	256	0.25	256
Ceftazidime/avibactam	23	47.8	n/a	256	0.12	256
Ceftolozane/tazobactam^a	2	0	n/a	64	64	64
Colistin^b	22	90.9	n/a	2	0.25	16
Doripenem^c	6	0	0	16	4	16
Gentamicin^d	17	47.1	n/a	32	0.25	32
Imipenem^e	1	n/a	0.0	16	16	16
Imipenem^f	22	13.6	9.1	16	0.25	16
Levofloxacin	24	4.2	8.3	16	0.25	16
Meropenem	24	0	0	32	16	32
Piperacillin/tazobactam	24	0	n/a	256	64	256
Tigecycline^g	2	50.0	n/a	2	0.25	8

Notes: ^aYears contributing data: 2017; ^bEnterobacterales species without intrinsic colistin resistance (Enterobacterales without Proteus spp., Providencia spp., Morganella spp. and Serratia spp.); ^cYears contributing data: 2015, 2016, 2017; ^dYears contributing data: 2018, 2019; ^eData only for Morganellaceae; ^fEnterobacterales species without Morganellaceae (Morganella spp.,Proteus spp. and Providencia spp.); ^gOrganisms contributing data were: E. coli, Citrobacter koseri; S - susceptible (standard dosing regimen); I – susceptible with increased exposure.

Abbreviation: n/a, not applicable.

Table 2 Susceptibility to Ceftazidime/Avibactam for MBL-Positive and MBL-Negative Subsets of Enterobacterales

Organism	Susceptible n (%)	Resistant n (%)
Enterobacterales (n=1523)	1506 (98.9)	17 (1.1)
Enterobacterales MBL-positive (n=18)	1 (5.6)	17 (94.4)
Enterobacterales MBL-negative (n=1505)	1505 (100)	0 (0)

Table 3 In vitro Activity of Ceftazidime/Avibactam and Other Commonly Used Antibiotics Tested Against Enterobacterales Isolates (n=1607) Collected from 2015 to 2019, Stratified by Genome (Ambler Classification of β-Lactamases)

Antibacterial	Class A												Class B				Class C						Class D
	CTX-M (n=376)		SHV-12* (n=9)		KPC-2 (n=2)		VEB (n=2)		SHV-OSBL (n=303)		TEM-OSBL (n=287)		VIM (n=10)		NDM (n=8)		AmpC (n=6)		CMY (n=7)		DHA (n=24)		OXA-48 (n=8)
	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I	% S	% I
Amikacin	86.4	n/a	77.8	n/a	50	n/a	0	n/a	88.5	n/a	84.7	n/a	90	n/a	62.5	n/a	66.7	n/a	100	n/a	75	n/a	37.5	n/a
Aztreonam	0	2.9	0	0	0	0	0	0	2.3	2	0.4	1.7	0	0	12.5	0	33.3	0	14.3	0	4.2	8.3	0	0
Cefepime	0.5	2.7	11.1	0	0	0	0	0	4.3	1	1.1	1.7	10	0	0	0	33.3	0	71.4	0	12.5	4.2	0	0
Ceftazidime	2.9	5.6	0	0	0	0	0	0	0.7	2.6	1.7	3.5	0	0	0	0	0	0	0	0	0	0	0	0
Ceftazidime/avibactam	97.6	n/a	33.3	n/a	100	n/a	100	n/a	98.4	n/a	98.6	n/a	10	n/a	0	n/a	100	n/a	100	n/a	100	n/a	100	n/a
Ceftolozane/tazobactam^a	67.4	n/a	0	n/a	0	n/a	–	–	61.3	n/a	59.7	n/a	0	n/a	–	–	–	–	50	n/a	40	n/a	0	n/a
Colistin^b	93.6	n/a	100	n/a	50	n/a	–	–	91.4	n/a	92.6	n/a	88.9	n/a	87.5	n/a	80	n/a	100	n/a	87.5	n/a	87.5	n/a
Doripenem^c	94.7	2.4	33.3	16.7	0	0	–	–	93.5	3	94	3	14.3	14.3	–	–	–	–	100	0	93.3	0	0	75
Gentamicin^d	45.8	n/a	33.3	n/a	100	n/a	0	n/a	48.2	n/a	38.8	n/a	33.3	n/a	50	n/a	33.3	n/a	66.7	n/a	22.2	n/a	25	n/a
Imipenem^e	n/a	100	n/a	0	–	–	n/a	100	–	–	n/a	100	n/a	0	–	–	n/a	100	n/a	100	–	–	–	–
Imipenem^f	91.7	2.9	37.5	12.5	0	0	–	–	91.8	3	93.7	2.8	11.1	11.1	0	0	40	0	66.7	16.7	75	0	37.5	50
Levofloxacin	15.2	9	22.2	22.2	0	0	0	0	13.2	9.6	13.9	10.5	10	40	0	0	0	0	28.6	0	0	0	0	0
Meropenem	88.8	6.7	55.6	11.1	0	50	100	0	87.8	8.3	90.9	6.3	30	30	0	0	50	50	71.4	28.6	75	25	50	37.5
Piperacillin/tazobactam	27.7	n/a	22.2	n/a	0	n/a	100	n/a	17.8	n/a	23	n/a	0	n/a	0	n/a	50	n/a	42.9	n/a	16.7	n/a	0	n/a
Tigecycline^g	97.1	n/a	100	n/a	–	–	–	–	100	n/a	96.3	n/a	–	–	100	n/a	–	–	100	n/a	–	–	–	–

Notes: *Coexistence of other resistance mechanisms is highly probable; ^aYears contributing data: 2017; ^bEnterobacterales species without intrinsic colistin resistance (Enterobacterales without Proteus spp., Providencia spp., Morganella spp. and Serratia spp.); ^cYears contributing data: 2015, 2016, 2017; ^dYears contributing data: 2018, 2019; ^eData only for Morganellaceae; ^fEnterobacterales species without Morganellaceae (Morganella spp., Proteus spp. and Providencia spp.); ^gOrganisms contributing data were: E. coli, Citrobacter koseri; S - susceptible (standard dosing regimen); I – susceptible with increased exposure.

Abbreviation: n/a, not applicable.

Figure 2 Ceftazidime/avibactam MIC distribution for P. aeruginosa (n=523) by phenotype. The dashed line shows the breakpoint for ceftazidime/avibactam according to EUCAST (EUCAST Clinical Breakpoint Tables v. 11.0). 56 isolates with MIC above the breakpoint was observed, among them 56 were MDR, 48 - DTR and 42 - CR.

Table 4 In vitro Activity of Ceftazidime/Avibactam and Other Commonly Used Antibiotics Tested Against 543 Pseudomonas aeruginosa Isolates Collected from 2015 to 2019

Antibacterial	n	% S	% I	MIC90	MIN (μg/mL)	MAX (μg/mL)
P. aeruginosa (n=543)
Amikacin	543	87.5	n/a	64	0.25	128
Aztreonam	523	n/a	74.6	32	0.25	256
Cefepime	543	n/a	74.6	32	0.12	64
Ceftazidime	543	n/a	71.5	64	0.5	256
Ceftazidime/avibactam	523	89.3	n/a	16	0.25	256
Ceftolozane/tazobactam^a	123	87.8	n/a	64	0.25	64
Colistin	523	99.4	n/a	2	0.25	16
Doripenem^b	262	n/a	73.3	16	0.06	16
Gentamicin^c	261	n/a	n/a	32	0.12	32
Imipenem	523	n/a	68.1	16	0.25	16
Levofloxacin	543	n/a	60.4	16	0.12	16
Meropenem	543	69.8	12.2	16	0.06	32
Piperacillin/tazobactam	543	n/a	69.4	128	0.12	256
Tigecycline^d	543	n/a	n/a	16	0.25	16
P. aeruginosa MDR (n=169)
Amikacin	169	60.4	n/a	128	1	128
Aztreonam	164	n/a	29.3	64	4	256
Cefepime	169	n/a	24.3	64	4	64
Ceftazidime	169	n/a	18.3	128	2	256
Ceftazidime/avibactam	164	65.9	n/a	64	0.5	256
Ceftolozane/tazobactam^a	38	60.5	n/a	64	0.5	64
Colistin	164	98.8	n/a	2	0.25	16
Doripenem^b	74	n/a	31.1	16	0.25	16
Gentamicin^c	90	n/a	n/a	32	0.25	32
Imipenem	164	n/a	31.1	16	0.5	16
Levofloxacin	169	n/a	18.9	16	0.25	16
Meropenem	169	28.4	17.8	32	0.25	32
Piperacillin/tazobactam	169	n/a	11.8	256	8	256
Tigecycline^d	169	n/a	n/a	16	0.5	16
P. aeruginosa DTR (n=101)
Amikacin	101	47.5	n/a	128	1	128
Aztreonam	96	n/a	36.5	64	4	256
Cefepime	101	n/a	12.9	64	8	64
Ceftazidime	101	n/a	6.9	256	4	256
Ceftazidime/avibactam	96	50.0	n/a	128	1	256
Ceftolozane/tazobactam^a	23	43.5	n/a	64	1	64
Colistin	96	100	n/a	2	0.25	2
Doripenem^b	39	n/a	5.1	16	0.5	16
Gentamicin^c	57	n/a	n/a	32	0.25	32
Imipenem	96	n/a	9.4	16	1	16
Levofloxacin	101	n/a	0	16	2	16
Meropenem	101	5.9	22.8	32	0.5	32
Piperacillin/tazobactam	101	n/a	6.9	256	8	256
Tigecycline^d	101	n/a	n/a	16	0.5	16
P. aeruginosa CR (n=98)
Amikacin	98	52.0	n/a	128	1	128
Aztreonam	93	n/a	34.4	64	4	256
Cefepime	98	n/a	27.6	64	4	64
Ceftazidime	98	n/a	26.5	256	4	256
Ceftazidime/avibactam	93	54.8	n/a	128	2	256
Ceftolozane/tazobactam^a	28	57.1	n/a	64	0.5	64
Colistin	93	100	n/a	2	0.5	2
Doripenem^b	48	n/a	0	16	4	16
Gentamicin^c	45	n/a	n/a	32	0.25	32
Imipenem	93	n/a	1.1	16	4	16
Levofloxacin	98	n/a	13.3	16	0.25	16
Meropenem	98	0	0	32	16	32
Piperacillin/tazobactam	98	n/a	19.4	256	8	256
Tigecycline^d	98	n/a	n/a	16	0.5	16

Notes: ^aYears contributing data: 2017; ^bYears contributing data: 2015, 2016, 2017; ^cYears contributing data: 2018, 2019, no breakpoint has been established; ^dno breakpoint has been established; S - susceptible (standard dosing regimen); I – susceptible with increased exposure.

Abbreviation: n/a, not applicable.

Table 5 Susceptibility to Ceftazidime/Avibactam for MBL-Positive and MBL-Negative Subsets of P. aeruginosa

Organism	Susceptible n (%)	Resistant n (%)
P. aeruginosa (n=523)	467 (89.3)	56 (10.7)
P. aeruginosa MBL-positive (n=32)	2 (6.3)	30 (93.8)
P. aeruginosa MBL-negative (n=491)	465 (94.7)	26 (5.3)

Figure 3 Antimicrobial susceptibility (P. aeruginosa) to ceftazidime/avibactam stratified by age.