Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012–2018

Stone, Gregory G.; Hackel, Meredith A.

doi:10.1186/s12941-022-00504-8

Annals of Clinical Microbiology and Antimicrobials

Table 2 Activity of ceftazidime-avibactam and comparator agents against levofloxacin-resistant E. coli; ATLAS, by region, 2012–2018

From: Antimicrobial activity of ceftazidime-avibactam and comparators against levofloxacin-resistant Escherichia coli collected from four geographic regions, 2012–2018

Antimicrobial	MIC₅₀ (mg/L)	MIC₉₀ (mg/L)	Range (mg/L)	%S	%I	%R
Africa/Middle East, ESBL-positive (N = 609)
Ceftazidime-avibactam	0.25	0.5	≤ 0.015– ≥ 256	99.7	–	0.3
Ceftazidime^a	32	128	0.12– ≥ 256	2.8	13.3	83.9
Cefepime^a	32	≥ 64	0.25– ≥ 64	2.5	7.2	90.3
Ampicillin	≥ 64	≥ 64	16– ≥ 64	0.0	–	100
Amoxicillin-clavulanate^a	16	32	1– ≥ 64	26.9	–	73.1
Piperacillin-tazobactam	8	128	≤ 0.25– ≥ 256	61.1	18.2	20.7
Aztreonam^a	64	128	2– ≥ 256	0.0	5.3	94.7
Imipenem	0.25	0.25	0.06– ≥ 16	99.3	0.3	0.3
Meropenem	0.03	0.06	0.015– ≥ 32	99.5	0.3	0.2
Colistin^b (N = 472)	0.5	1	≤ 0.06–8	99.2	–	0.8
Amikacin	4	16	0.5– ≥ 128	85.2	–	14.8
Tigecycline	0.25	0.5	0.06–4	96.2	–	3.8
Africa/Middle East, ESBL-negative (N = 532)
Ceftazidime-avibactam	0.12	0.25	≤ 0.015– ≥ 256	99.6	–	0.4
Ceftazidime	0.25	0.5	≤ 0.015– ≥ 256	93.0	1.3	5.6
Cefepime	≤ 0.12	1	≤ 0.12– ≥ 64	92.7	3.2	4.1
Ampicillin	≥ 64	≥ 64	1– ≥ 64	15.0	–	85.0
Amoxicillin-clavulanate	8	32	≤ 0.12– ≥ 64	56.0	–	44.0
Piperacillin-tazobactam	2	32	0.5– ≥ 256	82.3	5.6	12.0
Aztreonam	0.12	0.5	≤ 0.015– ≥ 256	93.0	1.5	5.5
Imipenem	0.12	0.25	0.06– ≥ 16	99.1	0.4	0.6
Meropenem	0.03	0.06	0.008–16	99.2	0.2	0.6
Colistin^b (N = 413)	0.25	1	≤ 0.06– ≥ 16	98.5	–	1.5
Amikacin	2	8	0.5– ≥ 128	94.4	–	5.6
Tigecycline	0.25	0.5	0.06–4	94.9	–	5.1
Asia/South Pacific, ESBL-positive (N = 1283)
Ceftazidime-avibactam	0.12	0.5	≤ 0.015– ≥ 256	97.0	–	3.0
Ceftazidime^a	16	128	0.25– ≥ 256	6.3	16.4	77.3
Cefepime^a	32	≥ 64	≤ 0.12– ≥ 64	1.5	11.0	87.5
Ampicillin	≥ 64	≥ 64	4– ≥ 64	0.2	–	99.8
Amoxicillin-clavulanate^a	16	32	2– ≥ 64	41.6	–	58.4
Piperacillin-tazobactam	4	128	0.5– ≥ 256	74.0	9.8	16.1
Aztreonam^a	32	128	0.06– ≥ 256	0.5	7.9	91.7
Imipenem	0.25	0.5	≤ 0.03– ≥ 16	96.5	0.3	3.2
Meropenem	0.03	0.12	0.008– ≥ 32	96.5	0.5	3.0
Colistin^b (N = 1012)	0.25	1	≤ 0.06– ≥ 16	98.8	–	1.2
Amikacin	4	16	0.5– ≥ 128	89.8	–	10.2
Tigecycline	0.25	0.5	0.03– ≥ 16	94.3	–	5.7
Asia/South Pacific, ESBL-negative (N = 1054)
Ceftazidime-avibactam	0.12	0.25	≤ 0.015– ≥ 256	99.4	–	0.6
Ceftazidime	0.25	32	≤ 0.015– ≥ 256	77.9	3.1	19.0
Cefepime	≤ 0.12	1	≤ 0.12– ≥ 64	91.4	3.9	4.7
Ampicillin	≥ 64	≥ 64	≤ 0.5– ≥ 64	17.0	–	83.0
Amoxicillin-clavulanate	8	32	≤ 0.12– ≥ 64	52.4	–	47.6
Piperacillin-tazobactam	2	32	0.25– ≥ 256	83.5	4.9	11.6
Aztreonam	0.12	16	≤ 0.015– ≥ 256	79.7	4.6	15.7
Imipenem	0.25	0.5	≤ 0.03– ≥ 16	99.3	0.2	0.5
Meropenem	0.03	0.06	≤ 0.004– ≥ 32	99.4	0.1	0.5
Colistin^b (N = 780)	0.25	1	≤ 0.06– ≥ 16	99.4	–	0.6
Amikacin	2	8	≤ 0.25– ≥ 128	96.5	–	3.5
Tigecycline	0.25	0.5	0.03–4	94.7	–	5.3
Europe, ESBL-positive (N = 2290)
Ceftazidime-avibactam	0.12	0.5	≤ 0.015– ≥ 256	99.6	–	0.4
Ceftazidime^a	16	128	0.12– ≥ 256	6.0	17.2	76.9
Cefepime^a	32	≥ 64	≤ 0.12– ≥ 64	4.6	12.6	82.8
Ampicillin	≥ 64	≥ 64	1– ≥ 64	0.3	–	99.7
Amoxicillin-clavulanate^a	16	32	≤ 0.12– ≥ 64	25.9	–	74.1
Piperacillin-tazobactam	8	128	≤ 0.25– ≥ 256	61.3	15.8	22.9
Aztreonam^a	32	128	0.5– ≥ 256	0.3	10.3	89.4
Imipenem	0.25	0.25	≤ 0.03– ≥ 16	99.0	0.4	0.6
Meropenem	0.03	0.06	≤ 0.004– ≥ 32	98.9	0.6	0.5
Colistin^b (N = 1754)	0.5	1	≤ 0.06– ≥ 16	99.1	–	0.9
Amikacin	4	16	0.5– ≥ 128	79.9	–	20.1
Tigecycline	0.25	0.5	≤ 0.015–4	96.3	–	3.7
Europe, ESBL-negative (N = 2373)
Ceftazidime-avibactam	0.12	0.25	≤ 0.015– ≥ 256	99.5	–	0.5
Ceftazidime	0.25	1	0.03– ≥ 256	91.0	2.4	6.7
Cefepime	≤ 0.12	1	≤ 0.12– ≥ 64	91.1	4.3	4.6
Ampicillin	≥ 64	≥ 64	≤ 0.5– ≥ 64	16.0	–	84.0
Amoxicillin-clavulanate	16	32	≤ 0.12– ≥ 64	47.8	–	52.2
Piperacillin-tazobactam	2	64	≤ 0.12– ≥ 256	79.6	5.1	15.3
Aztreonam	0.12	1	≤ 0.015– ≥ 256	91.4	2.6	6.0
Imipenem	0.12	0.25	≤ 0.03– ≥ 16	98.7	0.5	0.8
Meropenem	0.03	0.06	≤ 0.004– ≥ 32	99.2	0.4	0.4
Colistin^b (N = 1786)	0.25	1	≤ 0.06– ≥ 16	98.9	–	1.1
Amikacin	2	8	0.5– ≥ 128	95.0	–	5.0
Tigecycline	0.25	0.5	≤ 0.015–4	94.1	–	5.9
Latin America, ESBL-positive (N = 1567)
Ceftazidime-avibactam	0.12	0.5	≤ 0.015– ≥ 256	99.7	–	0.3
Ceftazidime^a	32	128	0.5– ≥ 256	4.3	10.7	84.9
Cefepime^a	32	32	≤ 0.12– ≥ 64	2.3	6.6	91.1
Ampicillin	≥ 64	≥ 64	8– ≥ 64	0.1	–	99.9
Amoxicillin-clavulanate^a	16	32	≤ 0.12– ≥ 64	25.3	–	74.7
Piperacillin-tazobactam	8	64	≤ 0.25– ≥ 256	63.8	17.7	18.5
Aztreonam^a	64	128	0.5– ≥ 256	0.1	6.4	93.5
Imipenem	0.12	0.25	0.06– ≥ 16	99.2	0.4	0.4
Meropenem	0.03	0.06	0.015– ≥ 32	99.0	0.6	0.4
Colistin^b (N = 1232)	0.25	1	≤ 0.06–8	99.1	–	0.9
Amikacin	4	16	0.5– ≥ 128	82.6	–	17.4
Tigecycline	0.25	0.5	≤ 0.015–4	95.8	–	4.2
Latin America, ESBL-negative (N = 1132)
Ceftazidime-avibactam	0.12	0.25	≤ 0.015–4	100	–	0.0
Ceftazidime	0.25	1	0.03– ≥ 256	91.1	1.7	7.2
Cefepime	≤ 0.12	1	≤ 0.12– ≥ 64	93.3	3.1	3.6
Ampicillin	≥ 64	≥ 64	1– ≥ 64	22.0	–	78.0
Amoxicillin-clavulanate	8	32	≤ 0.12– ≥ 64	56.0	–	44.0
Piperacillin-tazobactam	2	32	0.25– ≥ 256	84.9	4.4	10.7
Aztreonam	0.12	1	≤ 0.015– ≥ 256	90.5	1.9	7.6
Imipenem	0.12	0.25	≤ 0.03– ≥ 16	99.5	0.1	0.4
Meropenem	0.03	0.06	0.008– ≥ 32	99.4	0.4	0.3
Colistin^b (N = 885)	0.25	1	≤ 0.06– ≥ 16	99.1	–	0.9
Amikacin	2	8	≤ 0.25– ≥ 128	94.4	–	5.6
Tigecycline	0.25	0.5	≤ 0.015–4	95.5	–	4.5

– Indicates no breakpoint for the agent
ESBL, extended-spectrum β-lactamase; %I, percentage of isolates susceptible, increased exposure; MIC, minimum inhibitory concentration; MIC₅₀, MIC required to inhibit growth of 50% of isolates (mg/L); MIC₉₀, MIC required to inhibit growth of 90% of isolates (mg/L); %R, percentage of isolates resistant; %S, percentage of isolates susceptible, standard dosing
^aNot suitable for use in the treatment of infections caused by ESBL-positive isolates
^bColistin was included on the comparator panel from 2014 onwards

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