In vitro and in vivo Antimicrobial Activities of Ceftazidime/Avibactam Alone or in Combination with Aztreonam Against Carbapenem-Resistant Enterobacterales

Figures & data

Table 1 Modal MICs of CZA and ATM

Strain no.	Organism	Gene	Control MICs (µg/mL)
			CZA	ATM
3	C. freundii	NDM	>128	64
5	K. pneumoniae	NDM	>128	0.5
11	K. pneumoniae	KPC	4	>128
16	K. pneumoniae	KPC	4	>128
18	K. pneumoniae	KPC	1	>128
19	K. pneumoniae	KPC	2	>128
22	K. pneumoniae	KPC	1	>128
23	K. pneumoniae	NDM	>128	>128
26	K. pneumoniae	KPC	2	>128
30	K. pneumoniae	KPC	2	>128
38	K. pneumoniae	NDM	>128	>128
41	E. coli	NDM	>128	>128
43	K. pneumoniae	KPC	0.5	>128
44	K. pneumoniae	KPC	0.5	>128
46	K. pneumoniae	KPC	0.25	>128
49	K. pneumoniae	KPC	0.5	>128
50	K. pneumoniae	KPC	0.5	>128
52	K. pneumoniae	KPC	<0.125	>128
53	K. pneumoniae	KPC	0.25	64
58	E. cloacae	IMP	>128	>128
59	K. pneumoniae	KPC	0.5	>128
62	K. pneumoniae	KPC	0.25	>128
65	K. pneumoniae	KPC	0.5	>128
67	K. pneumoniae	KPC	0.25	>128
69	E. coli	NDM	>128	<0.25
77	K. pneumoniae	KPC	2	>128
90	E. coli	NDM	>128	>128
98	E. coli	NDM	>128	>128
102	E. coli	NDM	>128	128
106	E. coli	NDM	>128	64
108	K. pneumoniae	KPC	1	>128
110	K. pneumoniae	NDM	>128	128
111	E. coli	NDM	>128	4
112	K. oxytoca	NDM	>128	128
114	C. freundii	NDM	>128	>128
118	K. pneumoniae	KPC	0.5	>128
127	E. coli	NDM	>128	>128
128	E. coli	NDM	128	>128
aq6	K. pneumoniae	KPC+NDM	>128	>128
aq24	K. pneumoniae	KPC+IMP	>128	>128
aq25	K. pneumoniae	KPC+NDM	>128	>128
aq29	K. pneumoniae	KPC+NDM	>128	>128
aq30	E. coli	NDM	>128	>128
S1	E. coli	NDM	>128	32
S2	K. pneumoniae	NDM	>128	1
S3	E. cloacae	NDM	>128	>128
S4	E. cloacae	NDM	>128	128
S5	E. cloacae	NDM	>128	>128
S6	E. cloacae	NDM	>128	>128
S7	E. cloacae	NDM	>128	>128
S8	E. cloacae	NDM	>128	>128
S9	E. cloacae	NDM	>128	>128
S10	E. cloacae	NDM	>128	>128
S11	E. cloacae	NDM	>128	>128
S12	E. cloacae	NDM	>128	>128
S13	E. cloacae	NDM	>128	>128
S14	K. pneumoniae	KPC	0.5	>128
S15	K. pneumoniae	KPC	1	>128
S16	S. marcescens	KPC	0.5	32
S17	K. ozaenae	KPC	0.5	>128
S18	K. pneumoniae	KPC	1	>128
S19	K. pneumoniae	NDM	>128	1
S20	K. pneumoniae	KPC	0.5	>128
S21	E. cloacae	NDM	>128	1
S22	K. pneumoniae	KPC	1	>128
S23	K. pneumoniae	KPC	1	>128
ET1	K. pneumoniae	OXA	1	0.5

Table 2 The FIC Value and Ratio Range of CZA Combined with ATM

Strain No.	CZA+ATM		Effect	CZA/ATM
	FICmin	FICmax
3	0.00488	0.50391	Synergistic	128/0.25–0.25/0.25
23	0.00195	0.50049	Synergistic	128/0.125–0.25/0.25
38	0.00146	0.12549	Synergistic	64/0.125–0.25/0.125
41	0.00146	0.50049	Synergistic	128/0.125–0.25/0.125
58	0.00146	0.06299	Synergistic	16/0.125–0.25/0.125
90	0.00488	0.50391	Synergistic	128/1–0.25/1
98	0.03223	0.51563	Synergistic	128/2–0.25/4
102	0.00488	0.50195	Synergistic	128/0.25–0.25/0.5
106	0.00879	0.25781	Synergistic	64/0.5–0.25/0.5
110	0.00879	0.50098	Synergistic	128/0.125–0.25/1
112	0.00195	0.50098	Synergistic	128/0.125–0.25/0.125
114	0.00285	0.50188	Synergistic	128/0.06–0.25/0.06
127	0.00781	0.50391	Synergistic	128/1–0.25/2
128	0.00391	0.25195	Synergistic	32/0.5–0.25/0.5
S1	0.00285	0.50188	Synergistic	128/0.06–0.25/0.06
S3	0.00195	0.50391	Synergistic	128/1–0.25/1
S4	0.00195	0.50098	Synergistic	128/0.125–0.25/0.125
S5	0.00195	0.50049	Synergistic	128/0.125–0.25/0.25
S6	0.00293	0.50195	Synergistic	128/0.5–0.25/0.5
S7	0.00879	0.50391	Synergistic	128/1–0.25/2
S8	0.00489	0.50195	Synergistic	128/0.5–0.25/1
S9	0.00293	0.50195	Synergistic	128/0.5–0.25/0.5
S10	0.00488	0.50391	Synergistic	128/1–0.25/1
S11	0.00488	0.50195	Synergistic	128/0.5–0.25/1
S12	0.00293	0.50195	Synergistic	128/0.5–0.25/0.5
S13	0.00488	0.50391	Synergistic	128/1–0.25/1
aq6	0.00879	0.50781	Synergistic	128/2–0.25/2
aq24	0.00293	0.50098	Synergistic	128/0.25–0.25/0.25
aq25	0.00293	0.50953	Synergistic	128/0.5–0.25/0.5
aq29	0.00293	0.50098	Synergistic	128/0.25–0.25/0.5
aq30	0.00285	0.50188	Synergistic	128/0.06–0.25/0.06

Notes: + – combine, / – interval between the MIC of CZA and ATM.

Abbreviations: CZA, ceftazidime/avibactam; ATM, aztreonam.

Figure 1 Bactericidal curve plots of ceftazidime/avibactam at various concentrations against KPC-producing Klebsiella pneumoniae No. 18.

Figure 2 Bactericidal curve plots of ceftazidime/avibactam combined with aztreonam against NDM-producing Escherichia coil No. 90.

Figure 3 Bactericidal curve plots of ceftazidime/avibactam combined with aztreonam against IMP-producing Enterobacter cloacae No. 58.

Figure 4 Therapeutic efficacy of ceftazidime/avibactam combined with aztreonam against MBLs strains in mouse. Mice were intraperitoneally infected with 5×10⁷ CFU of the bacteria and treated with PBS or ceftazidime/avibactam combined with aztreonam by subcutaneous injection. Their survival was assessed daily for 15 days (n=100). P<0.0001.