Quality Control Limits for Broth Microdilution Susceptibility Tests of Ten Antifungal Agents

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Article Figures & Data

Table 1.

Distribution of MICs reported by eight participating facilities each testing two control strains on 10 separate days

Antifungal agent and control strain^a	Incubation time (h)	No. of times the following MICs (μg/ml) were reported (n = 240)^b:
Antifungal agent and control strain^a	Incubation time (h)	≤0.016	0.03	0.06	0.12	0.25	0.5	1.0	2.0	4.0	8.0	16	32	64	128
Amphotericin B
C. parapsilosis	24				7	[1	120	109	3]
	48					20	[1	88	123	8]
C. krusei	24						[2	141	97]
	48							[10	202	28]
Flucytosine
C. parapsilosis	24			[43^c	152	43]	1	1
	48			4^c	[12	189	34]	1
C. krusei	24							1	5	[36	119	79]
	48									1	[74	162	3]
Fluconazole^d
C. parapsilosis	24				1	2	[4	55	91	15]
	48			1	2	1		[42	119	41]
C. krusei	24										[5	95	76	4]
	48											[4	108	98	0]
Voriconazole
C. parapsilosis	24	[9	86	141	4]
	48		[21	113	83	3]
C. krusei	24		4	[17	76	139	4]
	48				[0	110	125	5]
Ketoconazole
C. parapsilosis	24	6	[7	106	108	13]
	48		2	[23	114	82	17]	2
C. krusei	24		1	10	[32	74	123	0]
	48					[25	143	70]	1
Itraconazole
C. parapsilosis	24	5		4	[34	129	66]	1
	48			5	[28	149	57]	1
C. krusei	24		1	9	[23	68	136	3]
	48					[23	170	46]
Caspofungin (MK0991)
C. parapsilosis	24	6	1		1	[29	159	44]
	48				1	5	[11	143	67	2]			9	2^c
C. krusei	24			3	[22	98	116	1]
	48				4	[22	164	48]	2
Ravuconazole (BMS 207147)
C. parapsilosis	24	[9	93	121	7]	10
	48	3	[8	114	92	22]	1
C. krusei	24	6	10	[17	72	96	39]
	48					[83	152	5]
Posaconazole (SCH 56592)
C. parapsilosis	24	7		[36	119	77]	1
	48	1	1	[15	161	61]	1
C. krusei	24			[12	51	107	70]
	48			1	[3	93	140	3]
LY 303366
C. parapsilosis	24		4	3			2	[43	111	77	0]
	48			1				[31	83	123	2]
C. krusei	24	1	[8	130	75	23]	2	1
	48	1	2	[59	108	44	14]	10	2

↵a C. parapsilosis ATCC 22019 and C. krusei ATCC 6258.
↵b Proposed QC limits are indicated by brackets.
↵c MICs outside the range of flucytosine or caspofungin that were actually tested.
↵d Data from one laboratory were excluded because MICs of the control drug, amphotericin B, were outside of the proposed limits; another laboratory reported only 48-h readings. A third laboratory experienced growth failures with two lots of broth, especially after 24 h. Consequently, the total number of evaluable fluconazole MICs was less than the 240 expected test results.

Table 2.

Proposed MIC ranges of various antifungal agents for two quality control strains of Candida spp. when tested by the NCCLS microdilution procedure

Antifungal agent	MIC (μg/ml) ranges for microdilution tests with:
	C. parapsilosisATCC 22019 at:		C. krusei ATCC 6258 at:
	24 h	48 h	24 h	48 h
Amphotericin B	0.25–2.0	0.5–4.0	0.5–2.0	1.0–4.0
Flucytocine	0.06–0.25	0.12–0.5	4.0–16	8.0–32
Fluconazole	0.5–4.0	1.0–4.0	8.0–64	16–128
Voriconazole	0.016–0.12	0.03–0.25	0.06–0.5	0.12–1.0
Ketoconazole	0.03–0.25	0.06–0.5	0.12–1.0	0.25–1.0
Itraconazole	0.12–0.5	0.12–0.5	0.12–1.0	0.25–1.0
Caspofungin (MK0991)	0.25–1.0	0.5–4.0	0.12–1.0	0.25–1.0
Ravuconazole (BMS 207147)	0.016–0.12	0.03–0.25	0.06–0.5	0.25–1.0
Posaconazole (SCH 56592)	0.06–0.25	0.06–0.25	0.06–0.5	0.12–1.0
LY303366	1.0–8.0	1.0–8.0	0.03–0.25	0.06–0.5