In vitro Effect of the Combination of Aztreonam and Amoxicillin/Clavulanic Acid Against Carbapenem-Resistant Gram-Negative Organisms Producing Metallo-β-Lactamase

Figures & data

Table 1 Characteristics of the Drug Resistance Genes and Results of 59 MBL-Producing GNOs in the Checkerboard Microdilution Assay [Number (Rate%)]

Group	Number	MBL Genes			ESBL Genes						FICI Interpretation
		blaNDM	blaIMP	blaVIM	blaTEM	blaSHV	blaCTX-M-1 Group	blaCTX-M-9 Group	blaOXA-10	blaPER	Synergy	Partial Synergy	Additive	Indifference
Total	59	7	45	7	18	20	8	3	11	2	34	12	4	9
		(11.9%)	(76.2%)	(11.9%)	(30.5%)	(33.9%)	(13.6%)	(5.1%)	(18.6%)	(3.4%)	(57.6%)	(20.3%)	(6.7%)	(15.3%)
Enterobacteriaceae	33	3	30	0	18	20	8	3	0	0	32	1	0	0
		(9.1%)	(90.9%)	(0%)	(54.5%)	(60.6%)	(24.2%)	(90.9%)	(0%)	(0%)	(97.0%)	(3.0%)	(0%)	(0%)
Pseudomonadales	26	4	15	7	0	0	0	0	11	2	2	11	4	9
		(15.4%)	(57.7%)	(26.9%)	(0%)	(0%)	(0%)	(0%)	(42.3%)	(7.7%)	(7.7%)	(42.3%)	(15.4%)	(34.6%)

Figure 1 Results of the Enterobacteriaceae isolates in the checkerboard microdilution assay. (A) FICI values of Enterobacteriaceae isolates. The interpretation of the FICI was as follows: ≤0.5, synergy; >0.5 to <1, partial synergy; =1, additive; >1 to <4, indifference. The dashed line is the line that divides the different interpretations. (B) Reduced times of the MIC_ATM and MIC_AMC in combination compared to the mono-antibiotic treatments. (C) MIC range of aztreonam in both the mono-ATM group and the combination group. (D) MIC range of amoxicillin/clavulanic acid both in the mono-AMC group and in the combination group.

Figure 2 Time-kill curves of four representative Enterobacteriaceae isolates. (A) Isolate Kpn1; (B) isolate Kpn6; (C) isolate Kpn8; (D) isolate Ecl6. Each isolate was tested by five technical replicates and four biological replicates.

Figure 3 Results of the Pseudomonadales isolates in the checkerboard microdilution assay. (A) FICI values of Pseudomonadales isolates. The interpretation of the FICI was as follows: ≤0.5, synergy; >0.5 to <1, partial synergy; =1, additive; >1 to <4, indifference. The dashed line is the line that divides the different interpretations. (B) Reduced times of the MIC_ATM and MIC_AMC in combination compared to the mono-antibiotic treatments. (C) MIC range of aztreonam in both the mono-ATM group and the combination group. (D) MIC range of amoxicillin/clavulanic acid both in the mono-AMC group and in the combination group.