In Vitro Susceptibilities to Caspofungin and Micafungin of Clinical Isolates of Candida Species

Hyun Woo Choi; Jong Hee Shin; Jin Sol Lee; Duck Cho; Myung Gun Shin; Soon Pal Suh; Dong Wook Ryang

doi:10.3343/kjlm.2006.26.4.275

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Choi, Shin, Lee, Cho, Shin, Suh, and Ryang: In Vitro Susceptibilities to Caspofungin and Micafungin of Clinical Isolates of Candida Species

Original Article

Korean J Leg Med 2006;26(4):275-281.

Published online: 10 February 2006

DOI: https://doi.org/10.3343/kjlm.2006.26.4.275

In Vitro Susceptibilities to Caspofungin and Micafungin of Clinical Isolates of Candida Species

Hyun Woo Choi, M.D., Jong Hee Shin, M.D., Jin Sol Lee, M.D., Duck Cho, M.D., Myung Gun Shin, M.D., Soon Pal Suh, M.D., Dong Wook Ryang, M.D.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea

Received 19 June 2006 Revised 21 July 2006 Accepted 21 July 2006

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Caspofungin and micafungin are echinochandins with potent activities against Candida species. However, in vitro susceptibility to these agents of clinical Candida isolates in Korea has not been fully surveyed. We determined minimum inhibitory concentrations (MICs) of caspofungin and micafungin against clinical isolates of Candida species.

Methods

A total of 107 blood isolates of Candida species (24 C. albicans, 25 C. tropicalis, 24 C. glabrata, 20 C. parapsilosis, 8 C. krusei, and 6 other Candida species) were tested by using the National Committee for Clinical Laboratory Standards M27-A2 broth microdilution methods. The in vitro antifungal activities and spectrum of caspofungin and micafungin were compared with those of amphotericin B, fluconazole, and itraconazole.

Results

Caspofungin and micafungin exhibited a broad-spectrum activity against Candida species: caspofungin MIC ranged from 0.125 to 1 μg/mL and micafungin MIC from ≤0.03 to 1 μg/mL. C. albicans, C. tropicalis and C. glabrata showed high susceptibility to caspofungin (MIC90, 0.25 to 0.5 μg/mL) and micafungin (MIC90, ≤0.03 μg/mL), whereas C. parapsilosis was less susceptible to both echinocandins (MIC90, 1 μg/mL). The MIC50 for caspofungin, micafungin, amphotericin B, fluconazole, and itraconazole were 0.25, ≤0.03, 0.5, 1, and 0.125 μg/mL, respectively. Caspofungin MIC50 of C. glabrata and C. krusei isolates with decreased susceptibility to azoles were 0.25 and 0.5 μg/mL, respectively, and micafungin MIC₅₀ were ≤0.03 and 0.125 μg/mL, respectively.

Conclusions

These data showed an excellent in vitro activity of caspofungin and micafungin against clinical strains of Candida species, including isolates with reduced susceptibility to azoles.

Keywords: Caspofungin, Micafungin, Candida, Antifungal susceptibility testing

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Table 1.

Distribution of caspofungin minimum inhibitory concentrations (MICs) for clinical isolates of Candida species

	End point^*	Incubation time (h)	N of occurrence at MIC (μg/mL) of
	End point^*	Incubation time (h)	≤0.03	0.06	0.12	0.25	0.5	1	2	4	8	16	>16
C. albicans (N=24)	MIC-0	24				20	4
		48				16	8
	MIC-2	24			14	10
		48			14	10
C. tropicalis (N=25)	MIC-0	24				5	19	1
		48				2	22	1
	MIC-2	24			1	23	1
		48			1	22	2
C. glabrata (N=24)	MIC-0	24				7	17
		48				1	13	10
	MIC-2	24				23	1
		48				22	2
C. parapsilosis (N=20)	MIC-0	24					2	18
		48						15	3				2
	MIC-2	24					15	5
		48					13	6	1
C. krusei (N=8)	MIC-0	24						8
		48						2	6
	MIC-2	24					6	2
		48						8
C. guilliermondii (N=3)	MIC-0	24					3
		48						3
	MIC-2	24				3
		48					1	2
C. pelliculosa (N=3)	MIC-0	24				1	2
		48					3
	MIC-2	24				3
		48				1	2
Total (N=107)	MIC-0	24				33	37	27
		48				19	46	31	9				2
	MIC-2	24			15	62	23	7
		48			15	55	20	16	1

^* MIC-0, the lowest drug concentration that supported no visible growth; MIC-2, the lowest drug concentrations that caused a prominent reduction of growth (>50% inhibition relative to control growth).

Table 2.

Distribution of micafungin MICs for clinical isolates of Candida species

	End point	Incubation time (h)	N of occurrence at MIC (μg/mL) of
	End point	Incubation time (h)	≤0.03	0.06	0.12	0.25	0.5	1	2	4	8	16	>16
C. albicans (N=24)	MIC-0	24	24
		48	24
	MIC-2	24	24
		48	24
C. tropicalis (N=25)	MIC-0	24	25
		48	25
	MIC-2	24	25
		48	25
C. glabrata (N=24)	MIC-0	24	24
		48	24
	MIC-2	24	24
		48	24
C. parapsilosis (N=20)	MIC-0	24			1	1	4	14
		48				1	1	14	4
	MIC-2	24			4	7	6	3
		48				6	3	11
C. krusei (N=8)	MIC-0	24			4	4
		48				8
	MIC-2	24			8
		48			2	6
C. guilliermondii (N=3)	MIC-0	24	3
		48					1	1		1
	MIC-2	24		2	1
		48		1	1	1
C. pelliculosa (N=3)	MIC-0	24	2	1
		48	2	1
	MIC-2	24	3
		48	3
Total (N=107)	MIC-0	24	78	1	5	5	4	14
		48	75	1		9	2	15	4	1
	MIC-2	24	76	2	13	7	6	3
		48	76	1	3	13	3	11

Table 3.

In vitro susceptibilities of 107 Candida isolates to 5 antifungal agents

Species	Antifungal agent	MIC (μg/mL)			R^* (%)	SDD^* (%)
Species	Antifungal agent	Range	50%	90%	R^* (%)	SDD^* (%)
C. albicans	Caspofungin^†	0.125–0.25	0.125	0.25
(N=24)	Micafungin^†	≤0.03	≤0.03	≤0.03
	Amphotericin B	0.25–0.5	0.25	0.5
	Fluconazole	0.125–16	0.25	1		3
	Itraconazole	0.03–0.5	0.03	0.06		3
C. tropicalis	Caspofungin	0.25–0.5	0.25	0.5
(N=25)	Micafungin	≤0.03	≤0.03	≤0.03
	Amphotericin B	0.125–1	0.25	0.5
	Fluconazole	0.125–1	0.25	0.5
	Itraconazole	0.03–0.5	0.125	0.5		16
C. glabrata	Caspofungin	0.25–0.5	0.25	0.5
(N=24)	Micafungin	≤0.03	≤0.03	≤0.03
	Amphotericin B	0.25–1	0.5	1
	Fluconazole	2–32	16	32	8	29
	Itraconazole	0.25–8	0.5	1	25	42
C. parapsilosis	Caspofungin	0.5–1	0.5	1
(N=20)	Micafungin	0.125–1	0.25	1
	Amphotericin B	0.125–1	0.5	0.5
	Fluconazole	0.25–1	0.5	1
	Itraconazole	0.03–0.125	0.06	0.25
C. krusei	Caspofungin	0.5–1	0.5	ND
(N=8)	Micafungin	0.125	0.125	ND
	Amphotericin B	0.5–1	1	ND
	Fluconazole	32–64	64	ND	100
	Itraconazole	0.5–1	0.5	ND	50	50
Others^§	Caspofungin	0.25	0.25	ND
(N=6)	Micafungin	≤0.03–0.125	0.03	ND
	Amphotericin B	0.125–0.5	0.5	ND
	Fluconazole	0.25–4	4	ND
	Itraconazole	0.125–0.5	0.5	ND		50
Total	Caspofungin	0.125–1	0.25	1
(N=107)	Micafungin	≤0.03–1	≤0.03	1
	Amphotericin B	0.125–1	0.5	1
	Fluconazole	0.125–32	0.25	8	9	7
	Itraconazole	0.03–1	0.125	0.5	9	19

^* Percent R (resistant) and SDD (dose dependent susceptible) according to the NCCLS breakpoints for fluconazole and itraconazole.

^† Data are shown for MIC-2 at 24 h.

^‡ C. krusei isolates were considered to be intrinsically resistant to fluconazole regardless of the MIC.

^§ 3 C. guillermondii and 3 C. pelliculosa.

Abbreviation: ND, not determined due to low numbers of isolates.

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