TABLE 2.

FIC indexes for IVA, LUM, TEZ, ELX, and the triple combination ELX-TEZ-IVA in combination with common antibiotics against S. aureus isolates collected from CF patients^a

CFTR modulator	Antibiotic	FIC index for S. aureus isolate (stage)b
		Newman (ref)	A10 (early)	A12 (late)	J6 (early)	J9 (late)	F1 (early)	F5 (late)
IVA	AMX	0.5	1	2	1	0.5	0.625	0.625
	VAN	0.31	0.625	0.625	1	1	1	1
	TEC	0.31	1	1	1	0.75	1	0.75
	LZD	0.75	2	0.625	0.625	0.625	0.625	0.625
	AZM	0.531	2	2	2	2	2	2
LUM	AMX	0.625	0.625	2	1	0.625	0.625	0.625
	VAN	0.155	0.625	0.75	1	1	1	0.625
	TEC	0.185	0.625	0.625	2	2	0.625	0.75
	LZD	0.625	2	0.625	2	0.75	0.625	0.625
	AZM	0.75	1	1	2	2	1	2
TEZ	AMX	2	2	2	2	2	2	2
	VAN	2	2	2	2	2	2	2
	TEC	2	2	2	2	2	2	2
	LZD	2	2	2	2	2	2	2
	AZM	2	2	2	2	1	2	2
ELX	AMX	2	0.5	0.75	2	0.75	2	2
	VAN	2	0.563	2	2	2	2	2
	TEC	2	2	2	2	2	2	2
	LZD	2	2	2	2	2	2	2
	AZM	0.75	1	1	0.75	0.75	0.5	2
ETI	AMX	2	0.75	1	2	0.75	2	2
	VAN	2	2	2	2	2	2	2
	TEC	2	2	2	0.625	2	1	2
	LZD	2	2	2	2	2	2	2
	AZM	2	2	2	2	2	2	2

^aS. aureus isolates were grown for 20 h in the presence of serial dilutions of IVA, LUM, TEZ, ELX, or the triple combination ETI, along with the antibiotic AMX, VAN, TEC, LZD, or AZM. The concentrations of the CFTR modulators tested ranged from 0.5 to 32 μg/mL for IVA, LUM, and ELX and from 0.5/0.25/0.375 μg/mL to 32/16/24 μg/mL for the triple combination of ELX-TEZ-IVA (ETI), while antibiotics started from a concentration two-fold greater than the MIC₉₀ for the isolate to 32 times below the MIC₉₀ of the antibiotic alone. FIC indexes were calculated as (MIC₉₀ of CFTR modulator in combination/MIC₉₀ of CFTR alone) + (MIC₉₀ of antibiotic in combination/MIC₉₀ of antibiotic alone). Each experiment was performed at least two independent times (two technical replicates).

^bA FIC index of <0.5 indicated synergy (dark gray shading), a FIC index of ≥0.50 and <1.0 indicated an additive effect (light gray shading), and a FIC index of ≥1.0 and ≤4 indicated indifference (no shading). ref, reference strain; early, isolate collected at the early stage of chronic colonization; late, isolate collected after years of persistence, in the advanced stage of chronic colonization.