Table 4.

Studies on combination between fosfomycin and aztreonam. CB: checkerboard assay; TK: time–kill assay; ET: E-test.

Strain	Year and Country	Author	Number of Isolates	Known Resistance Mechanisms or Determinants (%)	FOS-Resistant (%)	Aztreonam-Resistant (%)	In Vitro (Methods)/In Vivo (Animal and Site of Infection)	Synergistic Effect (%)	Additive Effect (%)	Indifferent Effect (%)	Antagonistic Effect (%)	FOS Susceptibility Restoration (%)	Aztreonam Susceptibility Restoration (%)	Comments	Reference
Enterobacterales	2019, USA	Avery	48	48 not specified between: 8 E. coli: KPC (25%), NDM (75%), ESBL (62%); 35 Klebsiella spp: KPC (45%), NDM (40%); OXA (14%), VIM (8.%), ESBL (88%), fosA (44%); 2 Citrobacter spp: KPC (50%), NDM (50%), ESBL (50%), 4 E. cloacae: KPC (75%), NDM (25%), ESBL (75%)	20 (40%)	48 (100%)	in vitro (ET)	4 (8%)	13 (27%)	31 (64%)	0%	0%	0%	Data on synergism reported without distinction for bacterial strains. % of FOS-R isolates estimated on the basis of the reported MIC50.	[11]
	2019, USA	Flamm	20	-	-	-	in vitro (CB, TK)	5 (25%)	5 (25%)	1 (5%)	0%	-	-	For 9 isolates the efficacy of FOS + ATM remained indeterminate.	[38]
E. coli	2014, Sweden	Hickam	2	ESBL, OXA (50%)	0%	1 (50%)	in vitro (CB, TK)	2 (100%)	0%	0%	0%	-	-	-	[120]
K. pneumoniae	2014, Sweden	Hickam	1	ESBL, OXA (100%)	0%	1 (100%)	in vitro (CB, TK)	0%	1 (100%)	0%	0%	-	-	-	[120]
P. aeruginosa	2019, USA	Avery	103	-	NA (at least 71)	103 (100%)	in vitro (ET)	16 (15.5%)	68 (66%)	19 (18%)	0%	-	21 (13%)	-	[33]
	2019, USA	Flamm	5	-	-	-	in vitro (ET)	1 (20%)	3 (60%)	0%	0%	-	-	For 1 isolate the efficacy of FOS + ATM remained indeterminate.	[38]
	2002, Japan	Okazaki	30	-	15 (50%)	29 (96%)	in vitro (efficacy time index)	23 (76.%)	3 (10%)	4 (13%)	0%	4 (26%)	6 (20%)	-	[39]