Cotreatment with Aspirin and Azole Drugs Increases Sensitivity of Candida albicans in vitro

Figures & data

Table 1 The Clinical Features of the Patients Where the Strains Were Isolated

Strain (ZY)	Gender	Age	Source	Symptom
1	Female	53	Urine	Dysuria, urgency, and frequency
4	Female	61	Sputum	Fever, cough and sputum
7	Male	55	Faeces	Diarrhea
9	Male	56	Sputum	Fever, cough and sputum
11	Female	65	Sputum	Fever, cough and sputum
12	Female	65	Sputum	Fever, cough and sputum
15	Female	76	Sputum	Fever, cough and sputum
18	Male	24	Sputum	Fever, cough and sputum
20	Female	86	Sputum	Fever, cough and sputum
21	Female	56	Sputum	Fever, cough and sputum
22	Female	56	Sputum	Fever, cough and sputum
23	Female	40	Urine	Urgency, and frequency
24	Male	78	Urine	Dysuria, urgency, and frequency
26	Female	62	Urine	Dysuria, urgency, and frequency
27	Female	53	Sputum	Fever, cough and sputum
28	Female	26	Sputum	Fever, cough and sputum
30	Male	72	Sputum	Fever, cough and sputum
33	Female	30	Sputum	Fever, cough and sputum
35	Male	48	Sputum	Fever, cough and sputum
36	Male	88	Sputum	Fever, cough and sputum
38	Female	45	Sputum	Fever, cough and sputum
39	Male	19	Sputum	Fever, cough and sputum
40	Female	71	Faeces	Diarrhea
41	Female	45	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
42	Female	19	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
43	Female	38	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
44	Female	50	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
45	Female	22	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
46	Female	55	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
47	Female	30	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
48	Female	29	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
50	Female	48	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
51	Female	60	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
52	Female	27	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
53	Female	55	Vaginal secretion	Increased vaginal discharge accompanied by pruritus
55	Male	67	Urine	Dysuria, urgency, and frequency
56	Male	24	Urine	Dysuria, urgency, and frequency
63	Female	72	Urine	Dysuria, urgency, and frequency
64	Male	58	Urine	Dysuria, urgency, and frequency

Table 2 The Values of Minimum Inhibitory Concentration (MIC₅₀) Under Planktonic Conditions When Aspirin (ASA) and Fluconazole (FCA) Were Used

		MIC50 (μg/mL)						MIC50 (μg/mL)
		ASA		FCA				ASA		FCA
Strain (ZY)	FICI	Alone	Combination	Alone	Combination	Strain (ZY)	FICI	Alone	Combination	Alone	Combination
1	0.750	16,000	4000	64	32	38	0.500	8000	250	0.5	0.25
4	0.500	16,000	4000	16	8	39	0.125	16,000	500	64	8
7	0.125	16,000	4000	8	1	40	0.250	4000	2000	4	1
9	0.250	8000	2000	64	16	41	0.501	16,000	4000	64	32
11	0.500	8000	2000	4	2	42	0.126	8000	4000	16	2
12	0.504	4000	2000	64	0.25	43	0.127	16,000	8000	16	2
15	1.000	16,000	8000	32	16	44	0.250	16,000	2000	16	4
18	0.504	8000	4000	64	0.25	45	0.250	4000	2000	64	16
20	0.063	4000	500	64	4	46	0.125	8000	1000	32	4
21	0.126	4000	2000	16	2	47	0.501	8000	4000	64	32
22	1.125	8000	8000	64	8	48	0.251	8000	4000	64	16
23	1.000	16,000	8000	16	8	50	0.125	8000	1000	16	2
24	0.125	4000	1000	16	2	51	0.250	4000	1000	4	1
26	0.031	8000	500	16	0.5	52	0.126	16,000	4000	64	8
27	0.625	16,000	2000	4	2	53	0.032	4000	4000	8	0.25
28	0.313	4000	250	32	8	55	0.500	16,000	1000	32	16
30	1.000	8000	4000	8	4	56	0.064	16,000	8000	64	4
33	0.625	16,000	8000	64	8	63	0.125	4000	500	16	2
35	0.500	2000	500	32	8	64	0.500	8000	500	32	16
36	0.500	1000	250	2	0.5

Abbreviation: FICI, fractional inhibitory concentration index.

Table 3 The Values of Minimum Inhibitory Concentration (MIC₅₀) Under Biofilm Conditions When Aspirin (ASA) and Fluconazole (FCA) Were Used

		MIC50 (μg/mL)						MIC50 (μg/mL)
		ASA		FCA				ASA		FCA
Strain (ZY)	FICI	Alone	Combination	Alone	Combination	Strain (ZY)	FICI	Alone	Combination	Alone	Combination
1	0.500	32,000	8000	64	16	38	0.500	16,000	4000	8	2
4	0.375	16,000	4000	16	2	39	0.750	32,000	16,000	64	16
7	0.375	32,000	8000	16	2	40	0.188	16,000	2000	8	0.5
9	0.625	16,000	2000	64	32	41	1.000	16,000	8000	64	32
11	0.750	16,000	4000	8	4	42	0.500	8000	2000	16	4
12	1.000	8000	4000	64	32	43	1.004	16,000	16,000	128	0.5
15	0.500	16,000	4000	32	8	44	0.625	16,000	8000	32	4
18	0.625	8000	4000	128	16	45	0.625	8000	1000	64	32
20	0.375	16,000	2000	64	16	46	0.750	16,000	8000	32	8
21	0.250	8000	1000	32	4	47	0.625	16,000	2000	64	32
22	0.625	16,000	2000	32	16	48	1.000	8000	4000	32	16
23	1.000	16,000	8000	64	32	50	0.375	16,000	4000	32	4
24	1.250	16,000	16,000	32	8	51	0.375	8000	1000	8	2
26	0.188	32,000	2000	32	4	52	1.250	16,000	16,000	64	16
27	0.750	16,000	8000	8	2	53	0.563	8000	4000	16	1
28	0.750	8000	4000	64	16	55	0.375	16,000	4000	32	4
30	1.000	16,000	8000	8	4	56	0.750	16,000	8000	128	32
33	1.500	16,000	16,000	64	32	63	0.313	8000	2000	16	1
35	1.000	4000	2000	32	16	64	0.625	16,000	2000	16	8
36	0.625	8000	1000	8	4

Abbreviation: FICI, fractional inhibitory concentration index.

Table 4 The Interactions Between Aspirin (ASA) and Fluconazole (FCA), Itraconazole (ITR) or Voriconazole (VRC) Under Different Conditions

	ASA Combined with FCA		ASA Combined with ITR		ASA Combined with VRC
	Planktonic Conditions	Biofilm Conditions	Planktonic Conditions	Biofilm Conditions	Planktonic Conditions	Biofilm Conditions
Synergistic (FICI≤0.5)	17	18	17	18	17	19
Additive (0.5<FICI ≤1)	17	17	18	17	17	16
No interaction (1<FICI<4)	5	4	4	4	5	4
Antagonistic (FICI≥4)	0	0	0	0	0	0
Sensitization rate	43.59%	46.15%	43.59%	46.15%%	43.59%	48.72%

Abbreviation: FICI, fractional inhibitory concentration index.

Figure 1 Time–growth curves of Candida albicans ZY23. Time–growth curves of ZY23 treated with (A) fluconazole (FCA) (B) itraconazole (ITR) or (C) voriconazole (VRC) alone or in combination with different concentrations of aspirin (ASA).

Figure 2 Time-kill curves of Candida albicans ZY23 treated with (A) fluconazole (FCA) (B) itraconazole (ITR), and (C) voriconazole (VRC) alone or combination.