Synergistic Effects from Combination of Cryptotanshinone and Fosfomycin Against Fosfomycin-Susceptible and Fosfomycin-Resistant Staphylococcus aureus

Figures & data

Table 1 Fosfomycin MICs and FSSA and FRSA Strains Description

Pathogen	Strain	Reference/Source	Description	Fosfomycin MIC (μg/mL)
S. aureus	ATCC25923	American Type Culture Collection	Fosfomycin-susceptible reference strain	2
	#25	Lishui central hospital, zhejiang province	Clinical isolate with a G790A base substitution of MurA, and C299T base substitution of GlpT and G1044T base substitution of UhpT	128
	#28	Lishui central hospital, zhejiang province	Clinical isolate with a G790A base substitution of MurA, and C299T base substitution of GlpT and G1044T base substitution of UhpT	64
	#47	Lishui central hospital, zhejiang province	Clinical isolate with a G790A base substitution of MurA, and C299T base substitution of GlpT and G1044T base substitution of UhpT	64
	#87	Lishui central hospital, zhejiang province	Clinical isolate with a G790A base substitution of MurA, and C299T base substitution of GlpT and G1044T base substitution of UhpT	64
	#99	Lishui central hospital, zhejiang province	Clinical isolate with a G790A base substitution of MurA, and C299T base substitution of GlpT and G1044T base substitution of UhpT	64
	#122	Lishui central hospital, zhejiang province	Clinical isolate with a G248 base deletion of GlpT	2048
	#133	Lishui central hospital, zhejiang province	Clinical isolate with a G248 base deletion of GlpT	2048

Table 2 Determination of MIC of Cryptotanshinone and Fosfomycin Alone or in Combination Against FSSA and FRSA

Pathogen	Strain	Agent	MIC Alone (μg/mL)	MIC Combination (μg/mL)	FIC	FICI	Outcome
S. aureus	ATCC25923	Cryptotanshinone	8	2	0.25	0.3125	Synergistic
		Fosfomycin	2	0.125	0.0625
	#25	Cryptotanshinone	8	1	0.125	0.625	Partialsynergy
		Fosfomycin	128	64	0.5
	#28	Cryptotanshinone	8	1	0.125	0.375	Synergistic
		Fosfomycin	64	16	0.25
	#47	Cryptotanshinone	8	1	0.125	0.375	Synergistic
		Fosfomycin	64	16	0.25
	#87	Cryptotanshinone	8	1	0.125	0.375	Synergistic
		Fosfomycin	64	16	0.25
	#99	Cryptotanshinone	8	0.5	0.0625	0.5625	Partialsynergy
		Fosfomycin	128	32	0.5
	#122	Cryptotanshinone	128	32	0.25	0.3125	Synergistic
		Fosfomycin	2048	128	0.0625
	#133	Cryptotanshinone	128	32	0.25	0.3125	Synergistic
		Fosfomycin	2048	128	0.0625

Figure 1 Early addition of cryptotanshinone potentiates the fosfomycin activity against FSSA and FRSA strains. Time-kill curves of S. aureus ATCC 25,923 and #122 strains in presence of cryptotanshinone, and fosfomycin alone or in combination with cryptotanshinone for 24 h. FOS, fosfomycin, CPT, cryptotanshinone.

Figure 2 Cryptotanshinone potentiates the fosfomycin activity against FSSA and FRSA strains after second time addition of fosfomycin. Time-kill curves of S. aureus ATCC 25,923 and #122 strains in presence of cryptotanshinone and fosfomycin alone, or in combination with or without addition of fosfomycin for second time 4 h after bacterial addition. FOS, fosfomycin, CPT, cryptotanshinone.